Aijaz Ahmed

All Publications

Prevalence of Fatty Liver Disease and Fibrosis detected by Fibroscan in Adults in the United States, 2017-2018. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D., Cholankeril, G., Loomba, R., Ahmed, A. 2020
View details for DOI 10.1016/j.cgh.2020.08.017

View details for PubMedID 32801011
Early Impact of COVID-19 on Solid Organ Transplantation in the United States. Transplantation Cholankeril, G., Podboy, A., Alshuwaykh, O. S., Kim, D., Kanwal, F., Esquivel, C. O., Ahmed, A. 2020
Abstract

BACKGROUND: The regional impact of COVID-19 on solid organ transplantation in the United States (US) has not been fully evaluated.METHODS: A retrospective analysis of month-to-month trends on waitlist additions, waitlist deaths, and transplant surgeries between all United Network for Organ Sharing (UNOS) regions was performed. A linear regression model trained on historical data was used to estimate anticipated transplantation volume.RESULTS: All UNOS Regions reported a decrease in total waitlist additions and transplant surgeries. The largest decreases in total transplants were identified in Regions 1,2,6 and 9; with Regions 2, 7, 8 and 9 noting the largest decrease in waitlist additions. Six of the 11 regions noted increases in waitlist deaths, with UNOS Regions 9, 1, and 2, all located within the Northeast, noting the highest percent increase in waitlist deaths at 170%, 89%, and 54%, respectively. The largest reductions in SOT and waitlist deaths were seen in kidney and lung transplantation. Current transplantation volume is significantly lower than the low range of the 95% CI derived from the linear regression model (2182 vs 3110, p<0.05) CONCLUSIONS:: Significant decreases in total waitlist additions and transplant surgeries with increases in waitlist deaths were noted in the majority of US transplant domains. The impact was especially prevalent in areas with high burden of COVID-19 infection. National and regional strategies aimed at minimizing disruptions in transplantation are needed.

View details for DOI 10.1097/TP.0000000000003391

View details for PubMedID 32675741
Identification of Patients with Advanced Fibrosis Due to Nonalcoholic Fatty Liver Disease: Considerations for Best Practice. Journal of gastrointestinal and liver diseases : JGLD Augustin, S., Ahmed, A., Alkhouri, N., Canbay, A., Corless, L., Nakajima, A., Okanoue, T., Petta, S., Ratziu, V., Tsochatzis, E. A., Wong, V. W., Romero-Gomez, M. 2020; 29 (2): 235–45
Abstract

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) prevalence has increased in the past two decades, resulting in a significant but under-recognised public health burden. This impacts the prevalence of advanced fibrosis, end-stage liver disease and associated extrahepatic manifestations. To understand the challenges in recognising patients with advanced fibrosis due to NASH and develop a standardised approach to screen these patients, the authors of this document provided their opinions and expertise from practice and published evidence to identify key challenges and current approaches for diagnosing NASH. The severity of liver fibrosis due to NASH is the main indicator of associated morbidity and mortality outcomes. Therefore, identifying patients with, or at risk of, advanced fibrosis due to NASH and linking them to appropriate care is critical. This can be challenging due to a lack of awareness of NASH among healthcare professionals and a lack of standardised protocols for identifying patients. Simple noninvasive tests may provide an opportunity to facilitate early identification of these patients. This article proposes a simple, universally applicable diagnostic algorithm for use in clinical practice, that includes sequential use of noninvasive tests, ideally a biological marker and an imaging technique, which may help to facilitate early diagnosis of these patients. In the opinion of the authors, early detection of advanced fibrosis is fundamental in the efforts to halt the progression of NASH and diagnostic algorithms may facilitate pre-emptive interventions to curtail the disease.

View details for DOI 10.15403/jgld-775

View details for PubMedID 32530991
Decline in Annual Mortality of Hepatitis C Virus-related Hepatocellular Carcinoma in the United States, From 2009 to 2018. Gastroenterology Kim, D., Konyn, P., Cholankeril, G., Wong, R. J., Younossi, Z. M., Ahmed, A. 2020
View details for DOI 10.1053/j.gastro.2020.05.007

View details for PubMedID 32389664
High Prevalence of Concurrent Gastrointestinal Manifestations in Patients with SARS-CoV-2: Early Experience from California. Gastroenterology Cholankeril, G., Podboy, A., Aivaliotis, V. I., Tarlow, B., Pham, E. A., Spencer, S., Kim, D., Hsing, A., Ahmed, A. 2020
View details for DOI 10.1053/j.gastro.2020.04.008

View details for PubMedID 32283101
Road to identifying endpoint biomarkers in the treatment of nonalcoholic steatohepatitis: are we there yet? HEPATOBILIARY SURGERY AND NUTRITION Kim, D., Vazquez-Montesino, L., Ahmed, A. 2020; 9 (2): 244–46
View details for DOI 10.21037/hbsn.2019.10.02

View details for Web of Science ID 000521741700021
NAFLD Epidemiology, Emerging Pharmacotherapy, Liver Transplantation Implications and the Trends in the United States JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY Gadiparthi, C., Spatz, M., Greenberg, S., Iqbal, U., Kanna, S., Satapathy, S. K., Broder, A., Ahmed, A. 2020; 8 (2): 215–21
View details for DOI 10.14218/JCTH.2020.00014

View details for Web of Science ID 000546088000014
Trends in Hospitalizations for Clostridioides difficile Infection in End-Stage Liver Disease, 2005-2014. Digestive diseases and sciences Kim, D., Yoo, E. R., Li, A. A., Tighe, S. P., Cholankeril, G., Ahmed, A. 2020
Abstract

BACKGROUND: Data on the current estimates of the disease burden of Clostridioides difficile (C. difficile) infection in the setting of end-stage liver disease (ESLD) are emerging.AIMS: We examined the recent trends and predictors of hospitalizations and in-hospital mortality from C. difficile infection among hospitalizations with ESLD in the USA.METHODS: We performed a retrospective analysis using the National Inpatient Sample, 2005-2014. We defined ESLD and C. difficile infection using the International Classification of Diseases, Ninth Revision, Clinical Modification. Multivariable logistic regression was used to determine the risk factors that impacted hospitalization and mortality.RESULTS: The prevalence of coding for C. difficile infection in decompensated cirrhosis increased from 1.3% in 2005 to 2.7% in 2014, with an annual rate of 7.8%. In hospitalizations with hepatocellular carcinoma, C. difficile infection increased steadily from 1.0 to 1.7% with an annual incremental rate of 6.4%. Among hospitalizations with ESLD, each passing 2-year period, increasing age, female, higher Charlson index, accompanying infection, hepatorenal syndrome, and ascites were associated with C. difficile infection. Although C. difficile infection was an independent predictor of in-hospital mortality during hospitalization with decompensated cirrhosis (odds ratio 1.53, 95% confidence interval 1.44-1.63), the proportion of in-hospital mortality during hospitalization with C. difficile infection and decompensated cirrhosis decreased from 15.4% in 2005 to 11.1% in 2014, with an annual rate of -3.1% (95% CI -5.7% to -0.3%).CONCLUSIONS: While the prevalence of C. difficile infection in hospitalized patients with ESLD increased approximately twofold, the in-hospital mortality decreased significantly during the past decade.

View details for DOI 10.1007/s10620-020-06162-0

View details for PubMedID 32124196
Therapeutic Impact of Probiotic-based Diet Supplementation in Nonalcoholic Fatty Liver Disease Cholankeril, R., Ahmed, A., Varghese, R. W B SAUNDERS CO-ELSEVIER INC. 2020
View details for DOI 10.1016/j.metabol.2019.12.069

View details for Web of Science ID 000518472500070
Tenofovir versus entecavir in prevention of hepatocellular carcinoma and mortality in patients with chronic hepatitis B. Gut Kamal, F., Khan, M. A., Ahmed, A., Nair, S. 2020
View details for DOI 10.1136/gutjnl-2019-320554

View details for PubMedID 32041745
Inadequate Physical Activity and Sedentary Behavior Are Independent Predictors of Nonalcoholic Fatty Liver Disease. Hepatology (Baltimore, Md.) Kim, D., Vazquez-Montesino, L. M., Li, A. A., Cholankeril, G., Ahmed, A. 2020
Abstract

In general, physical activity (PA) and nonalcoholic fatty liver disease (NAFLD) have an inverse association. However, studies assessing the impact of the widely accepted Physical Activity Guidelines for Americans (PA Guidelines) on NAFLD are lacking. We performed a serial, cross-sectional analysis among adults by using the 2007-2016 United States National Health and Nutrition Examination Survey. NAFLD and advanced fibrosis were defined by using various noninvasive panels. A PA questionnaire assessed the leisure-time PA, occupation-related PA, transportation-related PA, and total sitting time as sedentary behavior. PA was categorized according to the PA Guidelines. Of the 24,588 individuals (mean age 47.4 years; 47.9% males), leisure-time PA (≥150 minutes/week) demonstrated 40% lower odds of NAFLD, whereas transportation-related PA was associated with 33% risk reduction in NAFLD. Analysis of total PA and sitting times simultaneously showed a dose-response association between sitting time and NAFLD (P for trend <0.001). Compliance with the PA Guidelines was lower in NAFLD versus non-NAFLD. The trends in compliance with the PA Guidelines for any type of PA remained stable in NAFLD except for a downtrend in transportation-related PA. In contrast, an improvement in compliance with the PA Guidelines for leisure-time was noted in the non-NAFLD cohort. Although PA demonstrated 10% stronger association with risk reduction of NAFLD in women, women showed a lower tendency of meeting the PA guidelines. Trends in total sitting time increased significantly regardless of NAFLD status. Conclusion: Sedentary behavior emerged as an independent predictor of NAFLD. Overall compliance with the PA Guidelines was lower in the NAFLD cohort with sex- and ethnicity-based differences. Implementation of these observations in clinical practice may improve our understanding as well as clinical outcomes.

View details for DOI 10.1002/hep.31158

View details for PubMedID 32012316
Gender and Racial Differences in Hospitalizations for Primary Biliary Cholangitis in the USA. Digestive diseases and sciences Adejumo, A. C., Akhtar, D. H., Dennis, B. B., Cholankeril, G., Alayo, Q., Ogundipe, O. A., Kim, D., Ahmed, A. 2020
Abstract

The prevalence, characteristics, burden and trends of primary biliary cholangitis (PBC) hospitalizations in the USA remain unclear.We identified primary PBC hospitalizations from the National Inpatient Sample (NIS) 2007 through 2014 using ICD-9-CM codes. We calculated the rates and trends of hospitalization for PBC per 100,000 US population among each gender (males and females) and racial categories (Whites, Blacks, Hispanics and other racial minorities), and measured the predictors of hospitalization, and of mortality, charges and length of stay (LOS) among PBC hospitalizations.There were 8460 (weighted: 41,191) PBC hospitalizations between 2007 and 2014. The mean national PBC hospitalization rate was 2.2 cases per 100,000 population (2.2/100,000), increasing from 1.7/100,000 (2007) to 2.5/100,000 (2014). From 2007 to 2014, the in-hospital mortality and LOS were unchanged while the charges increased from $65,993 to $73,093 ($225 million to $447 million overall expenses). Compared to Whites, the PBC hospitalization rate was 12% higher among Hispanics (RR: 1.12 [1.09-1.16]), 53% lower in Blacks (RR: 0.47 [0.45-0.49]) and 5% lower among other racial minorities (0.95 [0.91-0.99]). The rate was higher among females (RR:4.02 [3.93-4.12]) compared to males. On multivariate analysis, Blacks and other racial minorities, respectively, had higher odds of mortality (AOR: 1.47 [1.03-2.10] and 1.33 [0.96-1.84]), while other racial minorities had longer LOS (7.0 vs. 5.6 days) and higher hospital charges ($48,984 vs. $41,495) when compared to Whites.The hospitalization rate and burden of PBC in the USA have increased disproportionately among females and Hispanics with higher mortality in Blacks.

View details for DOI 10.1007/s10620-020-06402-3

View details for PubMedID 32535779
The impact of chronic liver disease in patients receiving active pharmacological therapy for opioid use disorder: One-year findings from a prospective cohort study. Drug and alcohol dependence Dennis, B. B., Akhtar, D., Cholankeril, G., Kim, D., Sanger, N., Hillmer, A., Chawar, C., D'Elia, A., Panesar, B., Worster, A., Marsh, D. C., Thabane, L., Samaan, Z., Ahmed, A. 2020; 209: 107917
Abstract

Despite the demonstrated benefit of methadone, the incidence opioid-related overdose, and its associated mortality continues to rise at an alarming rate. The impact of high prevalence comorbid features such as chronic liver disease (CLD) on methadone treatment response remain unclear.To determine whether CLD is associated with poor response to methadone treatment.Using a well-established multi-center cohort from the Genetics of Opioid Addiction Study (GENOA), we evaluated if presence of CLD among 1234 eligible patients with opioid use disorder receiving methadone treatment impacted health and behavioural responses to treatment. CLD was classified as any liver disorder/dysfunction present for a minimum period of six months. Serial urine toxicology assessments were used to determine treatment response. The effect of CLD was determined using a multi-variable logistic regression model.CLD was present in 25 % (n = 314) of the population. On average, patients with CLD were found to be older (mean age 44 vs 36 years, p < 0.0001), unemployed (81.8 % vs 61 %, p < 0.0001), and receiving government disability benefits at significantly higher rates (21.9 % vs 11 %, p < 0.0001). Increased levels of physical craving, emotional stress, as well as health risk behaviors were noted in CLD patients. Findings from the multi-variable model demonstrate a 68 % increased risk for dangerous opioid consumption behaviors (Odds Ration [OR]: 1.68, 95 % Confidence Interval [CI] 1.22, 2.31, p = 0.001) among patients with CLD. Methadone dose (OR: 0.76, 95 % CI 0.70, 0.81, p < 0.0001) was shown to be protective with a significant risk reduction of 24 % per 20 mg increase in methadone. Duration in treatment was also found to be protective (OR: 0.99, 95 % CI 0.97, 0.99, p < 0.0001).CLD poses a distinct risk for patients with opioid addiction. Closer drug monitoring, and substance use contingency management should be considered to reduce mortality risk in these patients.

View details for DOI 10.1016/j.drugalcdep.2020.107917

View details for PubMedID 32088589
Physical Activity, Measured Objectively, is Associated With Lower Mortality in Patients With Nonalcoholic Fatty Liver Disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D., Murag, S., Cholankeril, G., Cheung, A., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2020
Abstract

The association between physical activity (PA) and all-cause and cause-specific mortality from nonalcoholic fatty liver disease (NAFLD) requires investigation. We studied whether PA, measured by accelerometer, is associated with all-cause and cardiovascular mortality among individuals with NAFLD.We performed a longitudinal analysis using the 2003-2006 US National Health and Nutrition Examination Survey data of adults (20 years or older) and collecting mortality data through December 2015. NAFLD was defined based on hepatic steatosis index or US fatty liver index scores, in the absence of other causes of chronic liver disease. PA was measured from participants who wore accelerometers 10 hrs/day for a minimum of 4 days over a 7-day period and classified as total PA, moderate to vigorous PA (MVPA), and sedentary behavior.Over an average follow-up period of 10.6 years, increasing duration of total PA was associated with reduced risk of death, from any cause, in an age- and sex-adjusted model (hazard ratio [HR], 0.52; 95% CI, 0.32-0.86 for highest quartile vs lowest quartile; P for trend=.001) and multivariable model (HR, 0.46, 95% CI 0.28-0.75; P for trend<.001) among individuals with NAFLD. Increasing duration of MVPA was associated with a lower risk of death from any cause in individuals with NAFLD. Furthermore, longer total PA was associated with a lower risk for cardiovascular disease-related death in individuals with NAFLD (HR, 0.28; 95% CI, 0.08-0.98 for highest quartile vs lowest quartile; P for trend=.007). We did not find this association for cancer-related mortality in individuals with NAFLD. Increasing duration of sedentary behavior did not affect all-cause or cause-specific mortality in individuals with NAFLD.Longer total PA and MVPA, measured by accelerometers over a 7-day period, are associated with lower all-cause and cardiovascular mortality in individuals with NAFLD.

View details for DOI 10.1016/j.cgh.2020.07.023

View details for PubMedID 32683103
Road to identifying endpoint biomarkers in the treatment of nonalcoholic steatohepatitis: are we there yet? Hepatobiliary surgery and nutrition Kim, D., Vazquez-Montesino, L. M., Ahmed, A. 2020; 9 (2): 244–46
View details for DOI 10.21037/hbsn.2019.10.02

View details for PubMedID 32355692

View details for PubMedCentralID PMC7188524
PNPLA3 Gene Polymorphism and Liver- and Extrahepatic Cancer-related Mortality in the United States. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Wijarnpreecha, K., Scribani, M., Raymond, P., Harnois, D. M., Keaveny, A. P., Ahmed, A., Kim, D. 2020
View details for DOI 10.1016/j.cgh.2020.04.058

View details for PubMedID 32360822
Longitudinal Change in Thyroid-stimulating Hormone and Risk of Nonalcoholic Fatty Liver Disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Chung, G. E., Kim, D., Kwak, M. S., Yim, J. Y., Ahmed, A., Kim, J. S. 2020
View details for DOI 10.1016/j.cgh.2020.02.039

View details for PubMedID 32109637
Low Thyroid Function in Nonalcoholic Fatty Liver Disease Is an Independent Predictor of All-Cause and Cardiovascular Mortality. The American journal of gastroenterology Kim, D., Vazquez-Montesino, L. M., Escober, J. A., Fernandes, C. T., Cholankeril, G., Loomba, R., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2020
Abstract

Higher levels of thyroid-stimulating hormone (TSH) in the euthyroid state can negatively affect the metabolic health, including nonalcoholic fatty liver disease (NAFLD). We studied the effect of TSH levels in the setting of normal levels of thyroid hormone on all-cause and cause-specific mortality stratified by NAFLD status.The National Health and Nutrition Examination Survey (NHANES) III from 1988 to 1994 and NHANES III-linked mortality data through 2015 were used. NAFLD was defined as ultrasonographically diagnosed hepatic steatosis without coexisting liver diseases. Subclinical hypothyroidism was defined as a TSH level over 4.5 mIU/L and "low-normal" thyroid function as higher TSH level (2.5-4.5 mIU/L) within the euthyroid reference range. The Cox proportional hazard model analyzed the all-cause mortality and cause-specific mortality.In a multivariate logistic regression analysis, individuals with low thyroid function demonstrated an association with NAFLD in a dose-dependent manner. During a median follow-up of 23 years, low thyroid function was associated with increased all-cause mortality only in the univariate model. Low thyroid function was associated with a higher risk for all-cause mortality in individuals with NAFLD and not in those without NAFLD. Furthermore, low thyroid function was associated with a higher risk for cardiovascular mortality in the entire population and among those with NAFLD but demonstrated no association with the non-NAFLD group.In this large nationally representative sample of American adults, low thyroid function was associated with NAFLD and a predictor of higher risk for all-cause and cardiovascular mortality in individuals with NAFLD.

View details for DOI 10.14309/ajg.0000000000000654

View details for PubMedID 32496342
Nonalcoholic Steatohepatitis is the Most Rapidly Increasing Indication for Liver Transplantation in the United States. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Younossi, Z. M., Stepanova, M., Ong, J., Trimble, G., AlQahtani, S., Younossi, I., Ahmed, A., Racila, A., Henry, L. 2020
Abstract

The profile of chronic liver disease (CLD) in the United States has changed due to obesity trends and advances in treatment of viral hepatitis. We assessed liver transplant listing trends by CLD etiology.Adult candidates for liver transplantation were selected from the Scientific Registry of Transplant Recipients (2002 through 2019). We calculated proportion trends for common CLD etiologies at time of placement on the wait list, including chronic infection with hepatitis B virus, chronic infection with hepatitis C virus (HCV), nonalcoholic steatohepatitis (NASH, including cryptogenic cirrhosis), alcohol-related liver disease (ALD) without or with chronic HCV infection, autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, in patients with and without hepatocellular carcinoma (HCC).From the 168,441 patients with known etiology and non-acute liver failure on the liver transplant waitlist, 27,799 patients (16.5%) had HCC. In 2002, the most common etiologies in patients without HCC were chronic HCV infection (37%) and ALD (16%), whereas only 5% had NASH. Among patients with HCC, 58% had chronic HCV infection and 10% had ALD and only 1% had NASH. In 2019, among patients without HCC, NASH was the second leading indication for liver transplantation (28% of patients), after ALD (38% of patients). Among patients with HCC, chronic HCV infection remained the leading indication (40% of patients) but NASH (24% of patients) surpassed ALD (16% of patients) to become the second leading indication. NASH was the leading indication in women without HCC (34%), in patients older than 54 years (36%), and in patients on Medicare (41%). In trend analysis, NASH was the most rapidly increasing indication for liver transplantation in patients without HCC (Kendall tau=0.97; P<.001) and in patients with HCC (tau=0.94; P<.0001).In an analysis of data from the Scientific Registry of Transplant Recipients (2002 through 2019), we found NASH to be the second most common indication for liver transplant in 2019, and the fastest increasing indication. In 2019, NASH was the leading indication for liver transplantation among women without HCC.

View details for DOI 10.1016/j.cgh.2020.05.064

View details for PubMedID 32531342
Implementation and Impact of Universal Pre-procedure Testing of Patients for COVID-19 prior to Endoscopy. Gastroenterology Podboy, A., Cholankeril, G., Cianfichi, L., Guzman, E., Ahmed, A., Banerjee, S. 2020
View details for DOI 10.1053/j.gastro.2020.06.022

View details for PubMedID 32562723
NAFLD Epidemiology, Emerging Pharmacotherapy, Liver Transplantation Implications and the Trends in the United States. Journal of clinical and translational hepatology Gadiparthi, C., Spatz, M., Greenberg, S., Iqbal, U., Kanna, S., Satapathy, S. K., Broder, A., Ahmed, A. 2020; 8 (2): 215–21
Abstract

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. The spread of obesity worldwide in pandemic proportions has led to a rapid rise of NAFLD in developed and developing countries alike. There are no approved pharmacological agents to treat steatohepatitis or advanced fibrosis but obeticholic acid recently has shown some promise in phase III trial. Currently, NAFLD is the number one etiology for simultaneous liver and kidney transplantation in the USA, second most common indication for liver transplantation (LT) and projected to become number one very soon. LT for NAFLD poses unique challenges, as these patients are generally older, obese and more likely to have a number of metabolic risk factors. Bariatric surgery is an option and can be considered if a structured weight loss program does not achieve the sustained weight loss goal. Comprehensive cardiovascular risk assessment and aggressive management of comorbid conditions are crucial in the LT evaluation process to improve post-transplant survival. Recurrent nonalcoholic steatohepatitis after LT is not uncommon, and thus warrants primary and secondary prevention strategies through a multidisciplinary approach. Prevalence of NAFLD in a donor population is a unique and growing concern that limits the access to quality liver grafts.

View details for DOI 10.14218/JCTH.2020.00014

View details for PubMedID 32832402

View details for PubMedCentralID PMC7438346
PNPLA3 Gene Polymorphism and Overall and Cardiovascular Mortality in the United States. Journal of gastroenterology and hepatology Wijarnpreecha, K., Scribani, M., Raymond, P., Harnois, D. M., Keaveny, A. P., Ahmed, A., Kim, D. 2020
Abstract

The association between palatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) polymorphism and mortality is not well understood. We investigated the impact of PNPLA3 I148M (rs738409) polymorphism on overall and cardiovascular mortality based on the presence of NAFLD.The Third National Health and Nutrition Examination Survey (NHANES) from 1991 to 1994 and NHANES III-linked mortality data through 31 December 2015 were utilized in this study.Of 4,814 participants, 50.7% were homozygous for the C-allele and 12.6% were homozygous for the G-allele. During a follow-up of 20 years, there were a total of 1,255 deaths, 422 attributed to cardiovascular disease. There was a significant association with overall mortality among those with the PNPLA3 I148M (rs738409) GG genotype (hazard ratio [HR] 1.34; 95% confidence interval [CI] 1.02-1.77) or G-allele (HR 1.22 95% CI 1.09-1.36) in the general population NAFLD with homozygous PNPLA3 I148M (rs738409) GG genotype had higher overall mortality after adjusting for multiple metabolic risk factors (hazard ratio [HR] 1.45; 95% confidence interval [CI] 1.01-2.08). The PNPLA3 I148M (rs738409) G-allele had a tendency of increased cardiovascular mortality in the total population. This association was not noted in those with NAFLD.The homozygous PNPLA3 I148M (rs738409) GG genotype showed an increase in overall mortality in the general population and NAFLD independent of multiple metabolic risk factors.

View details for DOI 10.1111/jgh.15045

View details for PubMedID 32220085
COVID-19 and liver injury: a meta-analysis. European journal of gastroenterology & hepatology Wijarnpreecha, K., Ungprasert, P., Panjawatanan, P., Harnois, D. M., Zaver, H. B., Ahmed, A., Kim, D. 2020
Abstract

The number of cases with coronavirus disease 2019 (COVID-19) has exceeded seven million worldwide. However, the data describing the global prevalence of liver injury associated with COVID-19 is lacking secondary to the novelty of this ongoing pandemic. Therefore, we conducted a meta-analysis to determine the association between COVID-19 and liver injury.A systematic literature search of indexed databases including, PubMed, Medline, and Embase databases from inception to 14 April 2020, was used to identify studies that reported data of liver chemistry in patients diagnosed with COVID 19. The overall prevalence of abnormal liver chemistry and relevant 95% confidence interval was used to estimate the pooled results studies.Sixty-four studies with 11 245 patients with COVID-19 were included. The pattern of abnormal liver enzymes was notable for higher aspartate aminotransferase (AST) than alanine aminotransferase (ALT) levels. The overall global prevalence of elevated AST, ALT, total bilirubin, gamma-glutamyltransferase (GGT), and alkaline phosphatase was 23.2, 21.2, 9.7, 15.0, and 4.0%, respectively. The prevalence of elevated AST was substantially higher among those with severe cases (45.5%) compared to non-severe cases (15.0%). Co-existing chronic liver disease presented up to 37.6% of patients with COVID-19.A fourth of COVID-19 patients had elevated liver enzymes and associated with disease severity. Our study may be used as a guide for clinicians and epidemiologists to proactively identify other sources of injury and illness in patients diagnosed with COVID-19. Intensive monitoring for liver injury may be needed in cases with severe COVID-19.

View details for DOI 10.1097/MEG.0000000000001817

View details for PubMedID 32639420
Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition. mBio Tal, M. C., Torrez Dulgeroff, L. B., Myers, L., Cham, L. B., Mayer-Barber, K. D., Bohrer, A. C., Castro, E., Yiu, Y. Y., Lopez Angel, C., Pham, E., Carmody, A. B., Messer, R. J., Gars, E., Kortmann, J., Markovic, M., Hasenkrug, M., Peterson, K. E., Winkler, C. W., Woods, T. A., Hansen, P., Galloway, S., Wagh, D., Fram, B. J., Nguyen, T., Corey, D., Kalluru, R. S., Banaei, N., Rajadas, J., Monack, D. M., Ahmed, A., Sahoo, D., Davis, M. M., Glenn, J. S., Adomati, T., Lang, K. S., Weissman, I. L., Hasenkrug, K. J. 2020; 11 (3)
Abstract

It is well understood that the adaptive immune response to infectious agents includes a modulating suppressive component as well as an activating component. We now show that the very early innate response also has an immunosuppressive component. Infected cells upregulate the CD47 "don't eat me" signal, which slows the phagocytic uptake of dying and viable cells as well as downstream antigen-presenting cell (APC) functions. A CD47 mimic that acts as an essential virulence factor is encoded by all poxviruses, but CD47 expression on infected cells was found to be upregulated even by pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that encode no mimic. CD47 upregulation was revealed to be a host response induced by the stimulation of both endosomal and cytosolic pathogen recognition receptors (PRRs). Furthermore, proinflammatory cytokines, including those found in the plasma of hepatitis C patients, upregulated CD47 on uninfected dendritic cells, thereby linking innate modulation with downstream adaptive immune responses. Indeed, results from antibody-mediated CD47 blockade experiments as well as CD47 knockout mice revealed an immunosuppressive role for CD47 during infections with lymphocytic choriomeningitis virus and Mycobacterium tuberculosis Since CD47 blockade operates at the level of pattern recognition receptors rather than at a pathogen or antigen-specific level, these findings identify CD47 as a novel potential immunotherapeutic target for the enhancement of immune responses to a broad range of infectious agents.IMPORTANCE Immune responses to infectious agents are initiated when a pathogen or its components bind to pattern recognition receptors (PRRs). PRR binding sets off a cascade of events that activates immune responses. We now show that, in addition to activating immune responses, PRR signaling also initiates an immunosuppressive response, probably to limit inflammation. The importance of the current findings is that blockade of immunomodulatory signaling, which is mediated by the upregulation of the CD47 molecule, can lead to enhanced immune responses to any pathogen that triggers PRR signaling. Since most or all pathogens trigger PRRs, CD47 blockade could be used to speed up and strengthen both innate and adaptive immune responses when medically indicated. Such immunotherapy could be done without a requirement for knowing the HLA type of the individual, the specific antigens of the pathogen, or, in the case of bacterial infections, the antimicrobial resistance profile.

View details for DOI 10.1128/mBio.01293-20

View details for PubMedID 32576678
Treating Alcohol Use Disorder in Chronic Liver Disease. Clinical liver disease Yoo, E. R., Cholankeril, G., Ahmed, A. 2020; 15 (2): 77–80
Abstract

http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-2-reading-yoo a video presentation of this article http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-2-interview-yoo an interview with the author Answer questions and earn https://www.wileyhealthlearning.com/Activity/7036145/disclaimerspopup.aspx.

View details for DOI 10.1002/cld.881

View details for PubMedID 32226621

View details for PubMedCentralID PMC7098671
Association of Digestive Symptoms and Hospitalization in Patients With SARS-CoV-2 Infection. The American journal of gastroenterology Cholankeril, G., Podboy, A., Aivaliotis, V. I., Pham, E. A., Spencer, S. P., Kim, D., Ahmed, A. 2020; 115 (7): 1129–32
Abstract

High rates of concurrent gastrointestinal manifestations have been noted in patients with corona virus disease 2019 (COVID-19); however, the association between these digestive manifestations and need for hospitalization has not been established.This is a retrospective review of consecutive patients diagnosed with COVID-19. A total of 207 patients were identified; 34.5% of patients noted concurrent gastrointestinal symptoms, with 90% of gastrointestinal symptoms being mild.In a multivariate regression model controlled for demographics and disease severity, an increased risk of hospitalization was noted in patients with any digestive symptom (adjusted odds ratio 4.84, 95% confidence interval: 1.68-13.94).The presence of digestive symptoms in COVID-19 is associated with a need for hospitalization.

View details for DOI 10.14309/ajg.0000000000000712

View details for PubMedID 32618665

View details for PubMedCentralID PMC7302101
Diet Quality and its Association with Nonalcoholic Fatty Liver Disease and All-cause and Cause-specific Mortality. Liver international : official journal of the International Association for the Study of the Liver Yoo, E. R., Kim, D., Vazquez-Montesino, L. M., Escober, J. A., Li, A. A., Tighe, S. P., Fernandes, C. T., Cholankeril, G., Ahmed, A. 2020
Abstract

Healthy diet has been recommended for nonalcoholic fatty liver disease (NAFLD), although it is not clear whether improving diet quality can prevent mortality. We aim to assess the impact of quality of diet on NAFLD and mortality in subjects with and without NAFLD.We performed cohort study using the Third National Health and Nutrition Examination Survey from 1988 to 1994 and linked mortality data through 2015. We used the Healthy Eating Index (HEI) scores to define diet quality, with higher HEI scores (Q4) indicating better adherence to dietary recommendations. NAFLD was defined as ultrasonographic hepatic steatosis.Multivariate analysis showed that subjects with higher diet quality were inversely associated with NAFLD in a dose-dependent manner. During the median follow-up of 23 years, having a higher diet quality was associated with reduction in risk of all-cause mortality in the age, sex, Race/ethnicity-adjusted hazard ratio (HR) (Q4, HR:0.60 95% CI: 0.52-0.68) and the multivariate model (Q4, HR:0.81 95% CI: 0.71-0.92). Higher diet quality was associated with a lower risk for all-cause mortality in subjects without NAFLD; however, this protective association with diet quality was not noted in those with NAFLD. Furthermore, a high diet quality was associated with a lower risk for cancer-related mortality in the total population and among those without NAFLD. This association was not noted in those with NAFLD.High diet quality was inversely associated with NAFLD and was positively associated with a lower risk for cancer-related and all-cause mortality in those without NAFLD.

View details for DOI 10.1111/liv.14374

View details for PubMedID 31910319
Regional Trends in Mortality from Alcohol-Induced Causes in the United States, 2000-2017. Journal of general internal medicine Cholankeril, G., Dennis, B. B., Kim, D., Ahmed, A. 2019
View details for DOI 10.1007/s11606-019-05442-4

View details for PubMedID 31792862
HOSPITALIZATION OUTCOMES AND READMISSION RATES ASSOCIATED WITH NONALCOHOLIC FATTY LIVER DISEASE IN THE US: A NATIONAL COHORT STUDY UTILIZING ICD-10 ADMINISTRATIVE DATA Murag, S., Yoo, E., Dennis, B., Adejumo, A., Hu, M., Kim, D., Ahmed, A., Cholankeril, G. WILEY. 2019: 745A–746A
View details for Web of Science ID 000488653502382
Sustained Decline of Noninvasive Fibrosis Index Values in Patients With Chronic Hepatitis C (CHC) With Sustained Virologic Response (SVR) After Receiving Direct-Acting Antiviral Agents (DAAs) Prabhakar, V., Lutchman, G., Ahmed, A., Nguyen, M. H., Daugherty, T., Kwo, P. LIPPINCOTT WILLIAMS & WILKINS. 2019: S553–S554
View details for DOI 10.14309/01.ajg.0000593348.53707.0b

View details for Web of Science ID 000509756002173
Pathogenesis of Insulin Resistance and Atherogenic Dyslipidemia in Nonalcoholic Fatty Liver Disease JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY Akhtar, D. H., Iqbal, U., Vazquez-Montesino, L., Dennis, B. B., Ahmed, A. 2019; 7 (4): 362–70
View details for DOI 10.14218/JCTH.2019.00028

View details for Web of Science ID 000504640600012
Low-Normal Thyroid Function Is Associated With Advanced Fibrosis Among Adults in the United States CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Kim, D., Yoo, E. R., Li, A. A., Fernandes, C. T., Tighe, S. P., Cholankeril, G., Hameed, B., Ahmed, A. 2019; 17 (11): 2379–81
View details for DOI 10.1016/j.cgh.2018.11.024

View details for Web of Science ID 000486629300005
Genetic Factors and Continental Ancestry Account for Some Disparities in Nonalcoholic Fatty Liver Disease Among Hispanic Subgroups CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Yoo, E. R., Ahmed, A., Kim, D. 2019; 17 (11): 2176–78
View details for DOI 10.1016/j.cgh.2019.04.034

View details for Web of Science ID 000486630000015
SEVERE IMPAIRMENT OF PATIENT-REPORTED OUTCOMES (PROs) IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS (HCV) INFECTION SEEN IN REAL-WORLD PRACTICES ACROSS THE WORLD: DATA FROM THE GLOBAL LIVER REGISTRY Younossi, Z. M., Yu, M., El Kassas, M., Esmat, G., Yilmaz, Y., Fernandez, M., Duseja, A. K., Isakov, V. A., Buti, M., Mendez-Sanchez, N., Papatheodoridis, G. V., Chan, W., George, J., Bugianesi, E., Romero-Gomez, M., Roberts, S. K., Younes, Z., Wong, V., Fan, J., Eguchi, Y., Gordon, S. C., Ahmed, A., Ong, J., Jacobson, I. M., Arrese, M., Rinella, M. E., Hamid, S. S., Younossi, I., Lam, B. P., Ziayee, M., Nader, F., Racila, A., Henry, L., Stepanova, M., Global NASH Council WILEY. 2019: 359A–360A
View details for Web of Science ID 000488653501138
DISPARITIES IN PATIENTS WITH AUTOIMMUNE LIVER DISEASES AWAITING LIVER TRANSPLANTATION - HISPANIC ETHNICITY OR MEDICARE/MEDICAID INSURANCE IS ASSOCIATED WITH SIGNIFICANTLY LOWER PROBABILITY OF RECEIVING LIVER TRANSPLANTATION Hanlon, C., Galoosian, A., Ahmed, A., Wong, R. J. WILEY. 2019: 858A
View details for Web of Science ID 000488653503105
PNPLA3 GENE POLYMORPHISM AND OVERALL AND CARDIOVASCULAR MORTALITY IN THE UNITED STATES Wijarnpreecha, K., Scribani, M., Raymond, P., Harnois, D. M., Keaveny, A., Ahmed, A., Kim, D. WILEY. 2019: 727A
View details for Web of Science ID 000488653502353
DIET QUALITY AND ITS ASSOCIATION WITH NONALCOHOLIC FATTY LIVER DISEASE AND MORTALITY - A POPULATION-BASED STUDY Yoo, E., Li, A., Cholankeril, G., Kim, D., Ahmed, A. WILEY. 2019: 726A
View details for Web of Science ID 000488653502351
THE IMPACT OF FUNCTIONAL STATUS AT TIME OF LIVER TRANSPLANTATION ON POST-TRANSPLANT SURVIVAL AMONG US ADULTS WITH AUTOIMMUNE-RELATED LIVER DISEASES: AN ANALYSIS OF THE 2004-2017 UNITED NETWORK FOR ORGAN SHARING DATABASE Galoosian, A., Hanlon, C., Ahmed, A., Wong, R. J. WILEY. 2019: 667A
View details for Web of Science ID 000488653502252
DIFFERENCES IN THE CLINICAL PROFILE OF THE MOST COMMON CAUSES OF CHRONIC LIVER DISEASE (CLD) ACROSS THE WORLD: DATA FROM THE GLOBAL LIVER REGISTRY. Younossi, Z. M., Yu, M., El Kassas, M., Esmat, G., Yilmaz, Y., Fernandez, M., Duseja, A. K., Isakov, V. A., Buti, M., Mendez-Sanchez, N., Papatheodoridis, G. V., Chan, W., George, J., Bugianesi, E., Romero-Gomez, M., Roberts, S. K., Younes, Z., Wong, V., Fan, J., Eguchi, Y., Gordon, S. C., Ahmed, A., Ong, J., Jacobson, I. M., Arrese, M., Rinella, M. E., Hamid, S. S., Younossi, I., Lam, B. P., Ziayee, M., Nader, F., Racila, A., Henry, L., Stepanova, M., Global NASH Council WILEY. 2019: 463A–465A
View details for Web of Science ID 000488653501312
CLINICAL AND PATIENT-REPORTED OUTCOMES DATA FOR PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) AND NON-ALCOHOLIC STEATOHEPATITIS (NASH) ACROSS THE WORLD: DATA FROM THE GLOBAL NASH REGISTRY Younossi, Z. M., Yu, M., El Kassas, M., Esmat, G., Yilmaz, Y., Fernandez, M., Duseja, A. K., Isakov, V. A., Buti, M., Mendez-Sanchez, N., Papatheodoridis, G. V., Chan, W., George, J., Bugianesi, E., Romero-Gomez, M., Roberts, S. K., Younes, Z., Wong, V., Fan, J., Eguchi, Y., Gordon, S. C., Ahmed, A., Ong, J., Jacobson, I. M., Rinella, M. E., Hamid, S. S., Ziayee, M., Younossi, I., Lam, B. P., Arrese, M., Nader, F., Racila, A., Henry, L., Stepanova, M., Global NASH Council WILEY. 2019: 749A–750A
View details for Web of Science ID 000488653502390
ETIOLOGY SPECIFIC LIVER TRANSPLANT (LT) LISTINGS AND DETERMINANTS OF WAITLIST MORTALITY AMONG PATIENTS WITH ACUTE ON CHRONIC LIVER FAILURE (ACLF) IN THE US. Tariq, R., Arora, S., Ahmed, A., Terrault, N., Lucey, M. R., Kuo, Y., Singal, A. K. WILEY. 2019: 161A–162A
View details for Web of Science ID 000488653500248
NATIONAL ESTIMATE OF THE FREQUENCY, TRENDS AND HEALTHCARE BURDEN OF CARE FRAGMENTATION IN READMISSIONS FOR END-STAGE LIVER DISEASE IN THE US Adejumo, A., Dennis, B., Cholankeril, G., Wong, R. J., Kim, D., Younossi, Z. M., Ahmed, A. WILEY. 2019: 449A
View details for Web of Science ID 000488653501287
NON-ALCOHOLIC STEATOHEPATITIS (NASH) IS THE MOST RAPIDLY GROWING CAUSE OF LISTING FOR LIVER TRANSPLANTATION: THE SCIENTIFIC REGISTRY OF TRANSPLANT RECIPIENTS (SRTR) DATA FROM 1994 TO 2018 Younossi, Z. M., Stepanova, M., Ong, J., Trimble, G., Ahmed, A., Alqahtani, S., Younossi, I., Racila, A. WILEY. 2019: 697A–698A
View details for Web of Science ID 000488653502304
TRENDS AND OUTCOMES ASSOCIATED WITH ALCOHOL-RELATED HOSPITALIZATIONS IN THE UNITED STATES: A RETROSPECTIVE COHORT STUDY Murag, S., Yoo, E., Dennis, B. B., Adejumo, A., Hu, M., Kim, D., Ahmed, A., Cholankeril, G. WILEY. 2019: 392A–393A
View details for Web of Science ID 000488653501192
CLINICAL AND PATIENT-REPORTED OUTCOMES (PROs) IN PATIENTS WITH CHRONIC HEPATITIS B VIRUS (HBV) INFECTION SEEN IN REAL-WORLD PRACTICES ACROSS THE WORLD: DATA FROM THE GLOBAL LIVER REGISTRY Younossi, Z. M., Yu, M., El Kassas, M., Esmat, G., Yilmaz, Y., Fernandez, M., Duseja, A. K., Isakov, V. A., Buti, M., Mendez-Sanchez, N., Papatheodoridis, G. V., Chan, W., George, J., Bugianesi, E., Romero-Gomez, M., Roberts, S. K., Younes, Z., Wong, V., Fan, J., Eguchi, Y., Gordon, S. C., Ahmed, A., Ong, J., Jacobson, I. M., Arrese, M., Rinella, M. E., Hamid, S. S., Younossi, I., Lam, B. P., Ziayee, M., Nader, F., Racila, A., Henry, L., Stepanova, M. WILEY. 2019: 577A–578A
View details for Web of Science ID 000488653502093
THE ROLE OF LOCOREGIONAL THERAPY (LRT), POST LRT IMAGING, AND EXPLANT PATHOLOGY AS PREDICTORS OF HEPATOCELLULAR CARCINOMA (HCC) RECURRENCE POST ORTHOTOPIC LIVER TRANSPLANT (OLT) Prabhakar, V., Dhanasekaran, R., Arjunan, V., Tulu, Z., Ahmed, A., Daugherty, T., Kumari, R., Patel, B., Kim, W., Goel, A., Esquivel, C. O., Concepcion, W., Melcher, M., Bonham, C., Gallo, A., Kwo, P. WILEY. 2019: 691A–692A
View details for Web of Science ID 000488653502295
IS IT GOOD IDEA TO OFFER TRANSPLANT EXCEPTION POINTS FOR SEPTUAGENARIANS WITH HEPATOCELLULAR CARCINOMA (HCC)? Arjunan, V., Prabhakar, V., Raghavan, S., Tulu, Z., Kambham, N., Ahmed, A., Kwo, P., Dhanasekaran, R. WILEY. 2019: 557A–558A
View details for Web of Science ID 000488653502055
CLINICOPATHOLOGICAL FEATURES OF NONALCOHOLIC STEATOHEPATITIS (NASH)-RELATED HEPATOCELLULAR CARCINOMA (HCC) Arjunan, V., Prabhakar, V., Raghavan, S., Tulu, Z., Kambham, N., Ahmed, A., Kwo, P., Dhanasekaran, R. WILEY. 2019: 548A
View details for Web of Science ID 000488653502038
Association between body size-metabolic phenotype and nonalcoholic steatohepatitis and significant fibrosis. Journal of gastroenterology Kim, D., Kim, W., Joo, S. K., Han, J., Kim, J. H., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2019
Abstract

BACKGROUND AND AIMS: Body size-metabolic phenotype may help predict whether or not individuals with nonalcoholic fatty liver disease (NAFLD) develop advanced liver disease. We studied the association of body size-metabolic phenotype with nonalcoholic steatohepatitis (NASH) and significant fibrosis.METHODS: Our cross-sectional study included 559 subjects (mean age of 53years; women 51%) with biopsy-proven NAFLD. Clinical, genetic, and histological characteristic features of NAFLD were evaluated. The metabolically unhealthy phenotype was defined by the presence of two or more metabolic components, while body size was categorized based on body mass index: obese (≥ 25kg/m2) or non-obese (< 25kg/m2). Body size-metabolic phenotypes were divided into four study groups: (1) non-obese metabolic syndrome (MS)-, (2) non-obese MS+, (3) obese MS-, and (4) obese MS+.RESULTS: Obese MS- and non-obese MS+groups demonstrated comparable levels of insulin resistance, adipose tissue insulin resistance indexes, and visceral adipose tissue (VAT) areas. The VAT area was significantly higher in the obese MS+group versus obese MS- group. However, the VAT to subcutaneous adipose tissue (SAT) ratio was highest in the non-obese MS+group. There was no difference in histology between the non-obese MS+, obese MS-, and obese MS+groups. Multivariate analyses adjusted for age, sex, smoking status, PNPLA3, TM6SF2, and VAT/SAT areas demonstrated an independent and dose-dependent relationship between the body size-metabolic phenotype and NASH or significant fibrosis.CONCLUSION: The non-obese MS+group displayed similar degree of hepatic histological severity compared to their obese MS- counterparts. Metabolic milieu beyond obesity may play a pathogenic role in non-obese MS+individuals who develop NASH with significant hepatic fibrosis.CLINICAL TRIAL NUMBER: NCT02206841.

View details for DOI 10.1007/s00535-019-01628-z

View details for PubMedID 31535207
Associations between sarcopenia and nonalcoholic fatty liver disease and advanced fibrosis in the USA EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY Wijarnpreecha, K., Kim, D., Raymond, P., Scribani, M., Ahmed, A. 2019; 31 (9): 1121–28
View details for DOI 10.1097/MEG.0000000000001397

View details for Web of Science ID 000493552900008
Trends in hospitalizations for chronic liver disease-related liver failure in the United States, 2005-2014 LIVER INTERNATIONAL Kim, D., Cholankeril, G., Li, A. A., Kim, W., Tighe, S. P., Hameed, B., Kwo, P. Y., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2019; 39 (9): 1661–71
View details for DOI 10.1111/liv.14135

View details for Web of Science ID 000485292200008
Suboptimal Use of Inpatient Palliative Care Consultation May Lead to Higher Readmissions and Costs in End-Stage Liver Disease. Journal of palliative medicine Adejumo, A. C., Kim, D., Iqbal, U., Yoo, E. R., Boursiquot, B. C., Cholankeril, G., Wong, R. J., Kwo, P. Y., Ahmed, A. 2019
Abstract

Background/Aims: Patients with end-stage liver disease (ESLD) have a high risk for readmission. We studied the role of palliative care consultation (PCC) in ESLD-related readmissions with a focus on health care resource utilization in the United States. Methods: We performed a retrospective longitudinal analysis on patients surviving hospitalizations with ESLD from January 2010 to September 2014 utilizing the Nationwide Readmissions Database with a 90-day follow-up after discharge. We analyzed annual trends in PCC among patients with ESLD. We matched PCC to no-PCC (1:1) using propensity scores to create a pseudorandomized clinical study. We estimated the impact of PCC on readmission rates (30- and 90-day), and length of stay (LOS) and cost during subsequent readmissions. Results: Of the 67,480 hospitalizations with ESLD, 3485 (5.3%) received PCC, with an annual increase from 3.6% to 6.7% (p for trend <0.01). The average 30- and 90-day annual readmission rates were 36.2% and 54.6%, respectively. PCC resulted in a lower risk for 30- and 90-day readmissions (hazard ratio: 0.42, 95% confidence interval [CI]: 0.38-0.47 and 0.38, 95% CI: 0.34-0.42, respectively). On subsequent 30- and 90-day readmissions, PCC was associated with decreased LOS (5.6- vs. 7.4 days and 5.7- vs. 6.9 days, p<0.01) and cost (US $48,752 vs. US $75,810 and US $48,582 vs. US $69,035, p<0.01). Conclusion: Inpatient utilization of PCC for ESLD is increasing annually, yet still remains low in the United States. More importantly, PCC was associated with a decline in readmission rates resulting in a lower burden on health care resource utilization and improvement in cost savings during subsequent readmissions.

View details for DOI 10.1089/jpm.2019.0100

View details for PubMedID 31397615
Depression is associated with non-alcoholic fatty liver disease among adults in the United States. Alimentary pharmacology & therapeutics Kim, D., Yoo, E. R., Li, A. A., Tighe, S. P., Cholankeril, G., Harrison, S. A., Ahmed, A. 2019
Abstract

BACKGROUND: Currently, the relationship between depression and non-alcoholic fatty liver disease (NAFLD) is not clearly defined.AIM: To determine whether depression is associated with NAFLD and NAFLD-related advanced fibrosis in a large population sample.METHODS: We performed a cross-sectional analysis using the 2007-2016 National Health and Nutrition Examination Survey database among adults (20years or older) in the United States (US). Depression and functional impairment due to depression were assessed with the Patient Health Questionnaire (PHQ-9). NAFLD was defined by utilising the US fatty liver index (USFLI), hepatic steatosis index (HSI) and the fatty liver index (FLI) in the absence of other causes of chronic liver disease. The presence and absence of advanced fibrosis in NAFLD were defined by Fibrosis-4 score.RESULTS: Of the 10484 subjects (mean age 47.0years; 48.8% men), the prevalence of depression and functional impairment due to depression was higher in subjects with NAFLD than in those without. Compared to subjects without depression, those with depression were 1.6-2.2-fold more likely to have NAFLD. In our multivariate analyses, depression_med was associated with increased risk of NAFLD using USFLI (odds ratio [OR] 1.48 95% confidence interval [CI] 1.17-1.87), HSI (OR 1.51 95% CI 1.04-2.19) and FLI (OR 2.01 95% CI 1.65-2.48), respectively. The addition of diabetes, obesity and lipid profile to the model reduced the ORs for depression, but the significance persisted. Depression was not associated with NAFLD-related advanced fibrosis.CONCLUSIONS: In a nationally representative sample of US adults, depression was independently associated with NAFLD.

View details for DOI 10.1111/apt.15395

View details for PubMedID 31328300
Liver Transplantation for Nonalcoholic Steatohepatitis: Pathophysiology of Recurrence and Clinical Challenges. Digestive diseases and sciences Samji, N. S., Verma, R., Keri, K. C., Singal, A. K., Ahmed, A., Rinella, M., Bernstein, D., Abdelmalek, M. F., Satapathy, S. K. 2019
Abstract

Nonalcoholic steatohepatitis is the fastest-growing indication for the liver transplant and a leading cause of hepatocellular carcinoma among patients listed for liver transplantation in the USA. Post-transplant nonalcoholic hepatic steatosis and steatohepatitis are frequent complications of liver transplantation. Nonalcoholic steatohepatitis poses a significant challenge in both pre- and post-transplant period due to its association with metabolic syndrome, coronary artery disease, chronic kidney disease, and obstructive sleep apnea. While optimal therapy is not yet available in the post-liver transplant setting, lifestyle interventions continue to remain as the mainstay of therapy for post-transplant nonalcoholic steatohepatitis. Early recognition with protocol biopsies and noninvasive modalities, along with modification of known risk factors, are the most effective methods to curtail the progression of nonalcoholic steatohepatitis in the absence of FDA-approved pharmacologic therapy.

View details for DOI 10.1007/s10620-019-05716-1

View details for PubMedID 31312990
Effects of Alcohol Consumption and Metabolic Syndrome on Mortality in Patients With Nonalcoholic and Alcohol-Related Fatty Liver Disease CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Younossi, Z. M., Stepanova, M., Ong, J., Yilmaz, Y., Duseja, A., Eguchi, Y., El Kassas, M., Castellanos-Fernandez, M., George, J., Jacobson, I. M., Bugianesi, E., Wong, V., Arrese, M., de Ledinghen, V., Romero-Gomez, M., Mendez-Sanchez, N., Ahmed, A., Wong, R., Papatheodoridis, G., Serfaty, L., Younossi, I., Nader, F., Ziayee, M., Afendy, A., Global NASH Council 2019; 17 (8): 1625-+
View details for DOI 10.1016/j.cgh.2018.11.033

View details for Web of Science ID 000471783300034
Trends in overall, cardiovascular and cancer-related mortality among individuals with diabetes reported on death certificates in the United States between 2007 and 2017 DIABETOLOGIA Kim, D., Li, A. A., Cholankeril, G., Kim, S. H., Ingelsson, E., Knowles, J. W., Harrington, R. A., Ahmed, A. 2019; 62 (7): 1185–94
View details for DOI 10.1007/s00125-019-4870-9

View details for Web of Science ID 000471176200009
Elevated urinary bisphenol A levels are associated with non-alcoholic fatty liver disease among adults in the United States LIVER INTERNATIONAL Kim, D., Yoo, E. R., Li, A. A., Cholankeril, G., Tighe, S. P., Kim, W., Harrison, S. A., Ahmed, A. 2019; 39 (7): 1335–42
View details for DOI 10.1111/liv.14110

View details for Web of Science ID 000475387700019
Increasing Trends in Transplantation of HCV-Positive Livers Into Uninfected Recipients CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Cholankeril, G., Li, A. A., Dennis, B. B., Toll, A. E., Kim, D., Bonham, C., Nair, S., Ahmed, A. 2019; 17 (8): 1634–36
View details for DOI 10.1016/j.cgh.2018.09.036

View details for Web of Science ID 000471783300035
Disparate Trends in Mortality of Etiology-Specific Chronic Liver Diseases Among Hispanic Subpopulations CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Kim, D., Li, A. A., Perumpail, R. B., Cholankeril, G., Gonzalez, S. A., Kim, W., Ahmed, A. 2019; 17 (8): 1607-+
View details for DOI 10.1016/j.cgh.2018.10.045

View details for Web of Science ID 000471783300032
Impact of sarcopenia on the progression of nonalcoholic fatty liver disease: a frequently forgotten association HEPATOBILIARY SURGERY AND NUTRITION Li, A. A., Ahmed, A., Kim, D. 2019; 8 (3): 260–61
View details for DOI 10.21037/hbsn.2018.12.10

View details for Web of Science ID 000470015000008
Nonalcoholic fatty liver disease in the over-60s: Impact of sarcopenia and obesity MATURITAS Wijampreecha, K., Panjawatanan, P., Aby, E., Ahmed, A., Kim, D. 2019; 124: 48–54
View details for DOI 10.1016/j.maturitas.2019.03.016

View details for Web of Science ID 000470193200009
Potential Mechanisms Influencing the Inverse Relationship Between Cannabis and Nonalcoholic Fatty Liver Disease: A Commentary NUTRITION AND METABOLIC INSIGHTS Dibba, P., Li, A. A., Cholankeril, G., Khan, M., Kim, D., Ahmed, A. 2019; 12
View details for DOI 10.1177/1178638819847480

View details for Web of Science ID 000471073200001
Liver transplantation for hepatitis C virus (HCV) non-viremic recipients with HCV viremic donors AMERICAN JOURNAL OF TRANSPLANTATION Kwong, A. J., Wall, A., Melcher, M., Wang, U., Ahmed, A., Subramanian, A., Kwo, P. Y. 2019; 19 (5): 1380–87
View details for DOI 10.1111/ajt.15162

View details for Web of Science ID 000471342300016
Trends in overall, cardiovascular and cancer-related mortality among individuals with diabetes reported on death certificates in the United States between 2007 and 2017. Diabetologia Kim, D., Li, A. A., Cholankeril, G., Kim, S. H., Ingelsson, E., Knowles, J. W., Harrington, R. A., Ahmed, A. 2019
Abstract

AIMS/HYPOTHESIS: The determination of diabetes as underlying cause of death by using the death certificate may result in inaccurate estimation of national mortality attributed to diabetes, because individuals who die with diabetes generally have other conditions that may contribute to their death. We investigated the trends in age-standardised mortality due to diabetes as underlying or contributing cause of death and cause-specific mortality from cardiovascular disease (CVD), complications of diabetes and cancer among individuals with diabetes listed on death certificates in the USA from 2007 to 2017.METHODS: Using the US Census and national mortality database, we calculated age-standardised mortality due to diabetes as underlying or contributing cause of death and cause-specific mortality rates among adults over 20years with diabetes listed on death certificates. A total of 2,686,590 deaths where diabetes was underlying or contributing cause of death were analysed. We determined temporal mortality rate patterns by joinpoint regression analysis with estimates of annual percentage change (APC).RESULTS: Age-standardised diabetes mortality rates compared among underlying cause of death, contributing cause of death and all-cause mortality were 32.2 vs 75.7 vs 105.1 per 100,000 individuals during the study period. The age-standardised mortality rates due to diabetes as underlying or contributing cause of death declined from 112.2 per 100,000 individuals in 2007 to 104.3 per 100,000 individuals in 2017 with the most pronounced decline noted from 2007 to 2014 (APC -1.4%; 95% CI -1.9%, -1.0%) and stabilisation in decline from 2014 to 2017 (APC 1.1%; 95% CI -0.6%, 2.8%). In terms of cause-specific mortality among individuals with diabetes listed on death certificates, the age-standardised mortality rates for CVD declined at an annual rate of 1.2% with a marked decline of 2.3% between 2007 and 2014. Age-standardised diabetes-specific mortality rates as underlying cause of death decreased from 2007 to 2009 (APC -4.5%) and remained stable from 2009 to 2017. Age-standardised mortality rates for cancer steadily decreased with an average APC of -1.4% (95% CI -1.8%, -1.0%) during the 11-year period. Mortality in the subcategory of CVD demonstrated significant differences.CONCLUSIONS/INTERPRETATION: Current national estimates capture about 30% of all-cause mortality among individuals with diabetes listed as underlying or contributing cause of death on death certificates. The age-standardised mortality due to diabetes as underlying or contributing cause of death and cause-specific mortality from CVD in individuals with diabetes listed as underlying or contributing cause of death plateaued from 2014 onwards except for hypertensive heart disease and heart failure.

View details for PubMedID 31011776
Genetic Factors and Continental Ancestry Account for Some Disparities in Nonalcoholic Fatty Liver Disease Among Hispanic Subgroups. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Yoo, E. R., Ahmed, A., Kim, D. 2019
View details for PubMedID 31009797
Association between body size-metabolic phenotype and non-alcoholic steatohepatitis and significant fibrosis Kim, W., Kim, D., Harrison, S., Younossi, Z., Ahmed, A. ELSEVIER SCIENCE BV. 2019: E300–E301
View details for Web of Science ID 000463481701164
Economic burden and healthcare utilization in nonalcoholic fatty liver disease HEPATOBILIARY SURGERY AND NUTRITION Yoo, E. R., Ahmed, A., Kim, D. 2019; 8 (2): 181–83
View details for DOI 10.21037/hbsn.2018.12.11

View details for Web of Science ID 000463372200020
Association between advanced fibrosis in fatty liver disease and overall mortality in terms of body size and body fat distribution Chung, G., Heo, N., Yim, J., Kwak, M., Kim, J., Ahmed, A., Kim, D. ELSEVIER SCIENCE BV. 2019: E293
View details for Web of Science ID 000463481701147
Predictors of outcomes for patients with non-alcoholic steatohepatitis undergoing liver transplantation in the United States Stepanova, M., Mishra, A., Younossi, I., Kim, D., Ahmed, A., Younossi, Z. ELSEVIER SCIENCE BV. 2019: E573
View details for Web of Science ID 000463481702232
Elevated urinary bisphenol A levels are associated with non-alcoholic fatty liver disease among adults in the United States Kim, D., Yoo, E., Li, A., Cholankeril, G., Tighe, S., Kim, W., Harrison, S., Ahmed, A. ELSEVIER SCIENCE BV. 2019: E300
View details for Web of Science ID 000463481701163
Elevated urinary bisphenol A levels are associated with non-alcoholic fatty liver disease among adults in the United States. Liver international : official journal of the International Association for the Study of the Liver Kim, D., Yoo, E. R., Li, A. A., Cholankeril, G., Tighe, S. P., Kim, W., Harrison, S. A., Ahmed, A. 2019
Abstract

BACKGROUND AND AIMS: The relationship between bisphenol A (BPA) and non-alcoholic fatty liver disease (NAFLD) is undefined. We studied the impact of BPA on NAFLD.METHODS: We performed a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) 2005-2014 among adults in the United States (US). NAFLD was diagnosed using the hepatic steatosis index (HSI) and the US fatty liver index (USFLI) in the absence of other causes of chronic liver diseases. The first sample using HSI consisted of 7605 adults. The second sample using USFLI consisted of 3631 participants with availability of fasting data.RESULTS: Of the first 7605 participants (mean age 47years, 48.4% male), the prevalence of NAFLD and abnormally elevated alanine aminotransferase (ALT) levels was correlated with urinary BPA levels (P<0.05). Compared to the reference group with lowest quartile of urinary BPA levels, those with the third and fourth quartiles were 81% and 53% more likely to develop NAFLD defined by HSI. In a multivariate model, the ORs for NAFLD in the third and fourth quartiles were 1.69 (95% CI 1.39-2.04) and 1.44 (95% CI 1.19-1.76) respectively (P for trend <0.001). In the second sample using USFLI, high BPA levels (fourth quartile) remained an independent predictor of NAFLD (OR 1.44, 95% CI 1.05-1.98, P for trend=0.012).CONCLUSIONS: High levels of urinary BPA were associated with NAFLD in a nationally representative sample of adults in the US. The pathophysiology remains unclear and warrants further investigation.

View details for PubMedID 30924602
The Epidemiology, Risk Profiling and Diagnostic Challenges of Nonalcoholic Fatty Liver Disease. Medicines (Basel, Switzerland) Iqbal, U., Perumpail, B. J., Akhtar, D., Kim, D., Ahmed, A. 2019; 6 (1)
Abstract

Nonalcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver damage from the more prevalent (75%⁻80%) and nonprogressive nonalcoholic fatty liver (NAFL) category to its less common and more ominous subset, nonalcoholic steatohepatitis (NASH). NAFLD is now the most common cause of chronic liver disease in the developed world and is a leading indication for liver transplantation in United States (US). The global prevalence of NAFLD is estimated to be 25%, with the lowest prevalence in Africa (13.5%) and highest in the Middle East (31.8%) and South America (30.4%). The increasing incidence of NAFLD has been associated with the global obesity epidemic and manifestation of metabolic complications, including hypertension, diabetes, and dyslipidemia. The rapidly rising healthcare and economic burdens of NAFLD warrant institution of preventative and treatment measures in the high-risk sub-populations in an effort to reduce the morbidity and mortality associated with NAFLD. Genetic, demographic, clinical, and environmental factors may play a role in the pathogenesis of NAFLD. While NAFLD has been linked with various genetic variants, including PNPLA-3, TM6SF2, and FDFT1, environmental factors may predispose individuals to NAFLD as well. NAFLD is more common in older age groups and in men. With regards to ethnicity, in the US, Hispanics have the highest prevalence of NAFLD, followed by Caucasians and then African-Americans. NAFLD is frequently associated with the components of metabolic syndrome, such as type 2 diabetes mellitus (T2DM), obesity, hypertension, and dyslipidemia. Several studies have shown that the adoption of a healthy lifestyle, weight loss, and pro-active management of individual components of metabolic syndrome can help to prevent, retard or reverse NAFLD-related liver damage. Independently, NAFLD increases the risk of premature cardiovascular disease and associated mortality. For this reason, a case can be made for screening of NAFLD to facilitate early diagnosis and to prevent the hepatic and extra-hepatic complications in high risk sub-populations with morbid obesity, diabetes, and other metabolic risk factors.

View details for PubMedID 30889791
Associations between sarcopenia and nonalcoholic fatty liver disease and advanced fibrosis in the USA. European journal of gastroenterology & hepatology Wijarnpreecha, K., Kim, D., Raymond, P., Scribani, M., Ahmed, A. 2019
Abstract

BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) may be associated with sarcopenia. This study aims to determine whether sarcopenia is independently associated with NAFLD and advanced fibrosis.PARTICIPANTS AND METHODS: Cross-sectional data from 11325 participants in the third National Health and Nutrition Examination Survey were analyzed. NAFLD was defined as the presence of hepatic steatosis from the ultrasound. Sarcopenia was defined as the skeletal muscle index.RESULTS: NAFLD was more common in participants with sarcopenia than in those without (46.7 vs. 27.5%). Univariate analysis showed that sarcopenia was associated with NAFLD [odds ratio (OR): 2.31; 95% confidence interval (CI): 2.01-2.64], which remained significant after adjustment for age, sex, ethnicity, metabolic risk factors (OR: 1.24; 95% CI: 1.03-1.48). This finding persisted after adjustment for C-reactive protein as a marker of chronic inflammation. NAFLD-associated advanced fibrosis was more common in participants with sarcopenia than in those without (7.8 vs. 1.6%). Sarcopenia was associated with NAFLD-associated advanced fibrosis independent of metabolic risk factors (OR: 1.79; 95% CI: 1.18-2.72).CONCLUSION: Sarcopenia was independently associated with increased odds of NAFLD and NAFLD-associated advanced fibrosis independent of well-defined risk factors. Interventions to strengthen muscle mass may reduce the burden of NAFLD and advanced fibrosis.

View details for PubMedID 30888971
Nonalcoholic Steatohepatitis Is the Fastest Growing Cause of Hepatocellular Carcinoma in Liver Transplant Candidates CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Younossi, Z., Stepanova, M., Ong, J. P., Jacobson, I. M., Bugianesi, E., Duseja, A., Eguchi, Y., Wong, V. W., Negro, F., Yilmaz, H., Romero-Gomez, M., George, J., Ahmed, A., Wong, R., Younossi, I., Ziayee, M., Afendy, A., Global Nonalcoholic Steatohepatiti 2019; 17 (4): 748-+
Abstract

Although hepatitis B and C have been the main drivers of hepatocellular carcinoma (HCC), nonalcoholic steatohepatitis (NASH) has recently become an important cause of HCC. The aim of this study was to assess the causes of HCC among liver transplant (LT) candidates in the United States.The Scientific Registry of Transplant Recipients (2002-2016) was used to estimate the trends in prevalence of HCC in LT candidates with the most common types of chronic liver disease: alcoholic liver disease (ALD), chronic hepatitis B (CHB), chronic hepatitis C, and NASH.158,347 adult LT candidates were included. Of these, 26,121 (16.5%) had HCC; this proportion increased from 6.4% (2002) to 23.0% (2016) (trend P < .0001). Over the study period, CHC remained the most common etiology for HCC (65%). The proportions of HCC accounted for by CHC and ALD remained stable (both trend P > .10), the proportion of CHB decreased 3.1-fold (P < .0001), while the proportion of NASH in HCC increased 7.7-fold (from 2.1% to 16.2%; P < .0001). Furthermore, since 2002, the prevalence of HCC in LT candidates with NASH increased 11.8-fold, while this rate increased 6.0-fold in CHB, 3.4-fold in ALD, and 2.3-fold in CHC (all P < .0001); the increasing trend in NASH was steeper than that for any other etiology (P < .0001 in a trend regression model). The proportion of LT candidates with HCC who ultimately received a transplant or died while waiting did not differ between etiologies (P > .05).Nonalcoholic steatohepatitis is the most rapidly growing cause of HCC among US patients listed for liver transplantation.

View details for PubMedID 29908364
Changing Trends in Etiology-Based and Ethnicity-Based Annual Mortality Rates of Cirrhosis and Hepatocellular Carcinoma in the United States HEPATOLOGY Kim, D., Li, A. A., Perumpail, B. J., Gadiparthi, C., Kim, W., Cholankeril, G., Glenn, J. S., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2019; 69 (3): 1064–74
View details for DOI 10.1002/hep.30161

View details for Web of Science ID 000459816500013
The Therapeutic Implications of the Gut Microbiome and Probiotics in Patients with NAFLD. Diseases (Basel, Switzerland) Perumpail, B. J., Li, A. A., John, N., Sallam, S., Shah, N. D., Kwong, W., Cholankeril, G., Kim, D., Ahmed, A. 2019; 7 (1)
Abstract

Recent breakthrough in our understanding pertaining to the pathogenesis of nonalcoholic fatty liver disease (NAFLD) has pointed to dysregulation or derangement of the gut microbiome, also known as dysbiosis. This has led to growing interest in probiotic supplementation as a potential treatment method for NAFLD due to its ability to retard and/or reverse dysbiosis and restore normal gut flora. A thorough review of medical literature was completed from inception through July 10, 2018 on the PubMed database by searching for key terms such as NAFLD, probiotics, dysbiosis, synbiotics, and nonalcoholic steatohepatitis (NASH). All studies reviewed indicate that probiotics had a beneficial effect in patients with NAFLD and its subset NASH. Results varied between studies, but there was evidence demonstrating improvement in liver enzymes, hepatic inflammation, hepatic steatosis, and hepatic fibrosis. No major adverse effects were noted. Currently, there are no guidelines addressing the use of probiotics in the setting of NAFLD. In conclusion, probiotics appear to be a promising option in the treatment of NAFLD. Future research is necessary to assess the efficacy of probiotics in patients with NAFLD.

View details for PubMedID 30823570
A functional subset of CD8+ T cells during chronic exhaustion is defined by SIRPalpha expression. Nature communications Myers, L. M., Tal, M. C., Torrez Dulgeroff, L. B., Carmody, A. B., Messer, R. J., Gulati, G., Yiu, Y. Y., Staron, M. M., Angel, C. L., Sinha, R., Markovic, M., Pham, E. A., Fram, B., Ahmed, A., Newman, A. M., Glenn, J. S., Davis, M. M., Kaech, S. M., Weissman, I. L., Hasenkrug, K. J. 2019; 10 (1): 794
Abstract

Prolonged exposure of CD8+ T cells to antigenic stimulation, as in chronic viral infections, leads to a state of diminished function termed exhaustion. We now demonstrate that even during exhaustion there is a subset of functional CD8+ T cells defined by surface expression of SIRPalpha, a protein not previously reported on lymphocytes. On SIRPalpha+ CD8+ T cells, expression of co-inhibitory receptors is counterbalanced by expression of co-stimulatory receptors and it is only SIRPalpha+ cells that actively proliferate, transcribe IFNgamma and show cytolytic activity. Furthermore, target cells that express the ligand for SIRPalpha, CD47, are more susceptible to CD8+ T cell-killing in vivo. SIRPalpha+ CD8+ T cells are evident in mice infected with Friend retrovirus, LCMV Clone 13, and in patients with chronic HCV infections. Furthermore, therapeutic blockade of PD-L1 to reinvigorate CD8+ T cells during chronic infection expands the cytotoxic subset of SIRPalpha+ CD8+ T cells.

View details for PubMedID 30770827
Race/ethnicity-based temporal changes in prevalence of NAFLD-related advanced fibrosis in the United States, 2005-2016. Hepatology international Kim, D., Kim, W., Adejumo, A. C., Cholankeril, G., Tighe, S. P., Wong, R. J., Gonzalez, S. A., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2019
Abstract

BACKGROUND AND AIM: Advanced fibrosis associated with nonalcoholic fatty liver disease (NAFLD) has been reported to have a higher risk of hepatic and non-hepatic mortality. We aim to study the recent trends in the prevalence of NAFLD-related advanced fibrosis in a large population sample.METHODS: Cross-sectional data from 28,739 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2016 were utilized. NAFLD was defined using the hepatic steatosis index (HSI) and the US fatty liver index (USFLI) in the absence of other causes of chronic liver disease. The presence and absence of advanced fibrosis in NAFLD was determined by the NAFLD fibrosis score, FIB-4 score, and aspartate aminotransferase-to-platelet ratio index.RESULTS: The prevalence of NAFLD-related advanced fibrosis increased from 2.6% [95% confidence interval (CI) 2.1-3.1] in 2005-2008 and 4.4% (95% CI 3.7-5.1) in 2009-2012, to 5.0% (95% CI 4.2-5.9) in 2013-2016 using HSI as the NAFLD prediction model; and from 3.3% (95% CI 2.5-4.5) in 2005-2008 and 6.4% (95% CI 3.7-5.1) in 2009-2012, to 6.8% (95% 5.3-8.7) in 2013-2016 using USFLI (p<0.01). A similar trend was observed in entire NHANES cohort regardless of NAFLD status. While the prevalence of advanced fibrosis increased steadily in non-Hispanic whites through the duration of the study, it leveled off during 2013-2016 in non-Hispanic blacks.CONCLUSIONS: Prevalence of advanced fibrosis associated with NAFLD increased steadily from 2005 to 2016. More importantly, race/ethnicity-based temporal differences were noted in the prevalence of NAFLD-related advanced fibrosis during the study.

View details for PubMedID 30694445
Trends in Mortality From Extrahepatic Complications in Patients With Chronic Liver Disease, From 2007 Through 2017. Gastroenterology Kim, D., Adejumo, A. C., Yoo, E. R., Iqbal, U., Li, A. A., Pham, E. A., Cholankeril, G., Glenn, J. S., Ahmed, A. 2019
Abstract

Trends of mortality associated with extrahepatic complications of chronic liver disease might be changing. We studied trends in mortality from extrahepatic complications of viral hepatitis, alcoholic liver disease (ALD), and nonalcoholic fatty liver disease in the United States (US).We performed a population-based study using US Census and the National Center for Health Statistics mortality records, from 2007 through 2017. We identified trends in age-standardized mortality using joinpoint trend analysis with estimates of annual percentage change.The liver-related mortality among patients with hepatitis C virus (HCV) infection increased from 2007 through 2013 and then decreased once patients began receiving treatment with direct-acting antiviral (DAA) agents, from 2014 through 2017. Among patients with HCV infection, the age-standardized mortality for extrahepatic cancers was 2.6%, for cardiovascular disease was 1.9%, and for diabetes was 3.3%. Among individuals with hepatitis B virus infection, liver-related mortality decreased steadily from 2007 through 2017. During the study age-standardized mortality from hepatitis B virus-related extrahepatic complications increased with an average annual percentage of 2.0%. Although liver-related mortality from ALD continued to increase, mortality from extrahepatic complications of ALD did not change significantly during the 11-year study. Among patients with nonalcoholic fatty liver disease, the cause of death was most frequently cardiovascular disease, which increased gradually over the study period, whereas liver-related mortality increased rapidly.In an analysis of US Census and the National Center for Health Statistics mortality records, we found that after widespread use of DAA agents for treatment of viral hepatitis, cause-specific mortality from extrahepatic cancers increased, whereas mortality from cardiovascular disease or diabetes increased only among patients with HCV infection. These findings indicate the need to reassess risk and risk factors for extrahepatic cancer, cardiovascular disease, and diabetes in individuals successfully treated for HCV infection with DAA agents.

View details for DOI 10.1053/j.gastro.2019.06.026

View details for PubMedID 31251928
Pathogenesis of Insulin Resistance and Atherogenic Dyslipidemia in Nonalcoholic Fatty Liver Disease. Journal of clinical and translational hepatology Akhtar, D. H., Iqbal, U., Vazquez-Montesino, L. M., Dennis, B. B., Ahmed, A. 2019; 7 (4): 362–70
Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the developed world, with a global prevalence of around 25%. NAFLD is considered to be the hepatic manifestation of metabolic syndrome and is strongly associated with obesity, insulin resistance and dyslipidemia. Insulin resistance plays a pivotal role in the development of NAFLD-related dyslipidemia, which ultimately increases the risk of premature cardiovascular diseases, a leading cause of morbidity and mortality in patients with NAFLD. Insulin affects hepatic glucose and lipid metabolism by hepatic or extrahepatic pathways. Aside from insulin resistance, several other factors also contribute to the pathogenesis of atherogenic dyslipidemia in patients with NAFLD. These include diet composition, gut microbiota and genetic factors, to name a few. The identification of potentially modifiable risk factors of NAFLD is of importance, so as to target those who may benefit from lifestyle changes and to help develop targeted therapies that decrease the risk of cardiovascular diseases in patients with NAFLD.

View details for DOI 10.14218/JCTH.2019.00028

View details for PubMedID 31915606

View details for PubMedCentralID PMC6943204
Post-transplant Outcome of Lean Compared to Obese Nonalcoholic Steatohepatitis in the United States: The Obesity Paradox. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Satapathy, S. K., Jiang, Y., Agbim, U., Wu, C., Bernstein, D. E., Teperman, L. W., Kedia, S. K., Aithal, G. P., Bhamidimarri, K. R., Duseja, A., Maiwall, R., Maliakkal, B., Jalal, P., Patel, K., Puri, P., Ravinuthala, R., Wong, V. W., Abdelmalek, M. F., Ahmed, A., Thuluvath, P. J., Singal, A. K. 2019
Abstract

Morbid obesity is considered a relative contraindication for LT (Liver Transplant). We investigated if BMI (lean vs. obese) is a risk factor for post-LT graft and overall survival in NASH and non-NASH patients.Using the UNOS database, LT recipients from 01/2002 to 06/2013 (age ≥18 yrs.) with follow up until 2017 were included. The association of BMI categories calculated at LT with graft and overall survival after LT were examined.After adjusting for confounders, all obesity cohorts (Overweight, Class I, Class II, and Class III obesity) among LT recipients for NASH had significantly reduced risk of graft and patient loss at 10 years follow up compared to the lean BMI cohort. In contrast, non-NASH group of LT recipients had no increased risk for graft and patient loss for overweight, Class I, Class II obesity groups, but had significantly increased the risk for graft (p<0.001) and patient loss (p=0.005) in the Class III obesity group.In this retrospective analysis of UNOS database, adult recipients selected for first LT, NASH patients with the lowest BMI have the worse long-term graft and patient survival as opposed to non-NASH patients where the survival was worse with higher BMI.

View details for DOI 10.1002/lt.25672

View details for PubMedID 31665561
Meeting Report: The Dallas consensus conference on liver transplantation for alcohol related hepatitis. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Asrani, S. K., Trotter, J., Lake, J., Ahmed, A., Bonagura, A., Cameron, A., DiMartini, A., Gonzalez, S., Im, G., Martin, P., Mathurin, P., Mellinger, J., Rice, J. P., Shah, V. H., Terrault, N., Wall, A., Winder, S., Klintmalm, G. 2019
Abstract

Liver transplantation (LT) for alcohol related hepatitis (AH) remains controversial. We convened a consensus conference to examine various aspects of LT for AH. The goal was not to unequivocally endorse LT for AH; instead it was to propose recommendations for programs that perform or plan to perform LT for AH. Criteria were established to determine candidacy for LT in the setting of AH and included the following: (1) AH patients presenting for the first time with decompensated liver disease that are non-responders to medical therapy without severe medical or psychiatric comorbidities (2) A fixed period of abstinence prior to transplantation is not required (3) Assessment with a multidisciplinary psychosocial team including a social worker and a addiction specialist/mental health professional with addiction and transplantation expertise. Supporting factors include lack of repeated unsuccessful attempts at addiction rehabilitation, lack of other substance use/dependency, acceptance of diagnosis/insight with commitment of patient/family to sobriety and formalized agreement to adhere to total alcohol abstinence and counseling. LT should be avoided in AH patients that are likely to spontaneously recover. Short- and long-term survival comparable to other indications for LT must be achieved. There should not be further disparity in LT either by indication, geography, or other sociodemographic factors. Treatment of alcohol use disorders should be incorporated into pre and post-LT care. The restrictive and focused evaluation process described in the initial LT experience for AH worldwide may not endure as this indication gains wider acceptance at more LT programs. Transparency in selection process is crucial with collection of objective data to assess outcomes and minimize center variation in listing. Oversight of program adherence is important to harmonize listing practices and outcomes.

View details for DOI 10.1002/lt.25681

View details for PubMedID 31743578
Kratom-Induced Cholestatic Liver Injury and Its Conservative Management. Journal of investigative medicine high impact case reports Fernandes, C. T., Iqbal, U., Tighe, S. P., Ahmed, A. 2019; 7: 2324709619836138
Abstract

Drug-induced liver injury (DILI) is a common cause of hepatotoxicity associated with prescription-based and over-the-counter exposure to medications and herbal supplements. Use of unapproved and inadequately tested herbal supplements can cause DILI. Therefore, thorough history-taking on exposure to herbal supplements must be an integral part of clinical evaluation of DILI. Kratom is an herbal supplement or remedy that has been known for its analgesic effects and has also been used for self-treatment of opiate withdrawals. A 52-year-old man was seen for evaluation of yellow discoloration of the eyes and skin. He reported taking kratom for right shoulder strain for at least a couple of months. On workup, his total bilirubin was noted to be 23.2 mg/dL, which peaked at 28.9 mg/dL. He was noted to have mild elevation of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Extensive laboratory tests were ordered and known causes of chronic liver disease ruled out. Magnetic resonance imaging of the abdomen was unremarkable without stigmata of portal hypertension or signs of chronic liver disease. He demonstrated no evidence of coagulopathy or hepatic encephalopathy during his illness. He underwent liver biopsy, which demonstrated histologic evidence of acute cholestatic hepatitis highly suspicious of DILI. He was advised to avoid kratom or other herbal supplements in future and prescribed ursodeoxycholic acid with significant improvement in his liver chemistries. Kratom is associated with significant liver enzymes derangements leading to DILI. Kratom is not approved for use in the United States and should be avoided.

View details for PubMedID 30920318
Extrahepatic Manifestations of Nonalcoholic Fatty Liver Disease. Gut and liver Li, A. A., Ahmed, A., Kim, D. 2019
Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and encompasses a spectrum of pathology from simple steatosis to inflammation and significant fibrosis that leads to cirrhosis. NAFLD and its comorbid conditions extend well beyond the liver. It is a multisystemic clinical disease entity with extrahepatic manifestations such as cardiovascular disease, type 2 diabetes, chronic kidney disease, hypothyroidism, polycystic ovarian syndrome, and psoriasis. Indeed, the most common causes of mortality in subjects with NAFLD are cardiovascular disease, followed by malignancies and then liver-related complications as a distant third. This review focuses on several of the key extrahepatic manifestations of NAFLD and areas for future investigation. Clinicians should learn to screen and initiate treatment for these extrahepatic manifestations in a prompt and timely fashion before they progress to end-organ damage.

View details for DOI 10.5009/gnl19069

View details for PubMedID 31195434
Recent advances in liver transplantation with HCV seropositive donors. F1000Research Murag, S., Dennis, B. B., Kim, D., Ahmed, A., Cholankeril, G. 2019; 8
Abstract

The paradigm shift from interferon-based to direct-acting antiviral (DAA) therapy for the treatment of hepatitis C virus (HCV) infection has revolutionized the field of liver transplantation. These advances in effective HCV treatment, along with the persistent shortage in available liver grafts, have encouraged investigators to assess the need for adopting more inclusive donor policies. Owing to the poor outcomes following liver transplantation with recurrent HCV infection, liver transplantation using HCV seropositive donors (non-viremic and viremic) had been restricted. However, as a result of the growing supply of HCV seropositive donors from the recent opioid epidemic along with the advent of efficacious DAA therapy to treat HCV recurrence, there has been an increasing trend to use HCV seropositive donors for both HCV seropositive and seronegative recipients. The review aims to discuss recent advances and associated outcomes related to the use of HCV seropositive grafts for liver transplantation.

View details for DOI 10.12688/f1000research.20387.1

View details for PubMedID 31942236

View details for PubMedCentralID PMC6944251
Impact of Nonmalignant Portal Vein Thrombosis in Transplant Recipients With Nonalcoholic Steatohepatitis LIVER TRANSPLANTATION Agbim, U., Jiang, Y., Kedia, S. K., Singal, A. K., Ahmed, A., Bhamidimarri, K., Bernstein, D. E., Harrison, S. A., Younossi, Z. M., Satapathy, S. K. 2019; 25 (1): 68–78
Abstract

Nonalcoholic fatty liver disease is an increasingly prevalent condition, and its more severe progressive state, nonalcoholic steatohepatitis (NASH), is currently the second most common indication for wait-listed adults in the United States. The association of portal vein thrombosis (PVT) prior to or at transplant and poor graft and patient outcomes is not well established, particularly among NASH patients who inherently have an increased hypercoagulable profile. Using the United Network for Organ Sharing data set, we analyzed graft and patient outcomes of patients transplanted for the indication of NASH with and without PVT. Of 3689 NASH transplant recipients, the prevalence of PVT was 12% (450 with PVT and 3239 without PVT). NASH transplant recipients with PVT had inferior graft and patient survival compared with NASH transplant recipients without PVT, even after adjusting for recipient and donor demographic characteristics, body mass index, synthetic dysfunction, and presence of diabetes. In a multivariate Cox regression model, NASH transplant recipients with PVT had a 37% increased risk of graft failure (hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.15-1.63; P < 0.001) and 31% increased risk of overall death (HR, 1.31; 95% CI, 1.09-1.58; P < 0.001) compared with NASH transplant recipients without PVT at transplant. This difference in graft and patient survival was most pronounced in the early posttransplant period. These results demonstrate that NASH patients with PVT have decreased graft and patient survival independent of recipient and donor factors.

View details for PubMedID 30091296
Economic burden and healthcare utilization in nonalcoholic fatty liver disease. Hepatobiliary surgery and nutrition Yoo, E. R., Ahmed, A., Kim, D. 2019; 8 (2): 181–83
View details for PubMedID 31098375

View details for PubMedCentralID PMC6503245
Nonalcoholic fatty liver disease in the over-60s: Impact of sarcopenia and obesity. Maturitas Wijarnpreecha, K., Panjawatanan, P., Aby, E., Ahmed, A., Kim, D. 2019; 124: 48–54
Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children and adults of all ethnicities. NAFLD is commonly seen in individuals with metabolic abnormalities, such as obesity and insulin resistance, which are closely associated with sarcopenia. Sarcopenia, defined as low muscle mass and impaired muscle function, is associated with NAFLD and worse outcomes in patients with NAFLD. As the world's elderly population and the prevalence of obesity continues to grow at an unprecedented rate, NAFLD and sarcopenia are projected to increase. Given that there are no approved pharmacologic treatments for NAFLD, it is imperative to gain a better understanding of the disease pathophysiology, to guide treatment options. Recent studies have given new insight into sarcopenic obesity, but there is no consensus on its definition. In this review, we attempt to address the impact of sarcopenia and obesity on NAFLD, especially in the elderly population.

View details for PubMedID 31097179
Temporal Trends Associated With the Rise in Alcoholic Liver Disease-related Liver Transplantation in the United States TRANSPLANTATION Cholankeril, G., Gadiparthi, C., Yoo, E. R., Dennis, B. B., Li, A. A., Hu, M., Wong, K., Kim, D., Ahmed, A. 2019; 103 (1): 131–39
View details for DOI 10.1097/TP.0000000000002471

View details for Web of Science ID 000455044100030
Trends in Hospitalizations for Chronic Liver Disease-related Liver Failure in the United States, 2005-2014. Liver international : official journal of the International Association for the Study of the Liver Kim, D., Cholankeril, G., Li, A. A., Kim, W., Tighe, S. P., Hameed, B., Kwo, P. Y., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2019
Abstract

Current estimates of the population-based disease burden of liver failure or end-stage liver disease (ESLD) are lacking. We investigated recent trends in hospitalizations and in-hospital mortality among patients with ESLD in the United States (US).A retrospective analysis was performed utilizing the National Inpatient Sample (NIS) from 2005 to 2014. We defined ESLD as either decompensated cirrhosis or hepatocellular carcinoma (HCC), criteria obtained from the International Classification of Diseases, Ninth Revision. Nationwide rates of hospitalization and in-hospital mortality were analyzed from 2005 to 2014.Hospitalization rates for decompensated cirrhosis during this period increased from 105.3/100,000 persons to 159.9/100,000 persons. In terms of HCC, hospitalization rates increased from 13.6/100,000 to 22.1/100,000. In patients with nonalcoholic fatty liver disease (NAFLD)-related decompensated cirrhosis, the hospitalization rate increased from 13.4/100,000 to 32.1/100,000 with an annual incremental increase of 10.6%, a magnitude two-fold higher than other etiologies. The proportion of NAFLD among hospitalizations with ESLD steadily increased from 12.7% to 20.1% for decompensated cirrhosis while the proportion of chronic hepatitis C (HCV) and alcoholic liver disease (ALD) declined (29.3% to 27.6% for HCV; 39.0% to 37.4% for ALD). Although the overall in-hospital mortality rates for ESLD declined during the study, mortality rates for NAFLD-related decompensated cirrhosis showed no significant change.Among etiologies of chronic liver disease, NAFLD demonstrated the fastest growing rate of hospitalizations in non-HCC patients with ESLD in the US. Our study highlights the need for a focus on NAFLD-related hospitalizations and its impact on resource utilization. This article is protected by copyright. All rights reserved.

View details for PubMedID 31081997
Increasing Mortality Among Patients With Diabetes and Chronic Liver Disease From 2007 Through 2017. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D., Cholankeril, G., Kim, S. H., Abbasi, F., Knowles, J. W., Ahmed, A. 2019
View details for DOI 10.1016/j.cgh.2019.06.011

View details for PubMedID 31220638
Hepatocellular carcinoma is leading in cancer-related disease burden among hospitalized baby boomers. Annals of hepatology Gadiparthi, C., Yoo, E. R., Are, V. S., Charilaou, P., Kim, D., Cholankeril, G., Pitchumoni, C., Ahmed, A. 2019
Abstract

Three fourths of chronic hepatitis C virus (HCV) infected adult patients in the United States (US) are born between 1945 and 1965, also known as baby boomers (BB). Prevalence of hepatocellular carcinoma (HCC) is raising in BB due to their advancing age and prolonged HCV infection. We evaluated inpatient hospitalization and mortality in BB associated with HCC.It is a retrospective cohort study utilizing the Healthcare Utilization Project-National Inpatient Sample (HCUP-NIS) database. From 2003 to 2012, top five primary cancer related hospitalization and mortality among BB were studied.Among 48,733 hospitalizations related to HCC in HCUP-NIS database from 2003 to 2012, BB accounted for 49.6% (24,210) whereas non-BB 50.4% (24,523). Within BB cohort, the top five cancers with the highest proportion of hospitalizations were HCC (46%), prostate (43%), kidney (41%), pancreas (33%), and bladder (21%). From 2003 to 2012, the proportion of HCC related hospitalizations represented by BB almost doubled (33.5 to 57.8%) whereas there was one-third reduction (66.4 to 42.1%) among non-BB. Similarly, HCC-related inpatient mortality in BB decreased by 28% (6.1 to 2.7 per 100,000 hospitalization) but it remained unchanged in non-BB (11.1 to 10.6). HCC accounted for 2nd highest mortality (4960 total deaths) among hospitalized BB behind pancreatic cancer. HCC related to HCV was disproportionately higher in BB compared to non-BB (50.6% vs. 19%; P<0.001).HCC ranks number one among the top five cancers with highest proportion of inpatient burden. Future studies should focus on understanding the underlying reasons for this ominous trend.

View details for DOI 10.1016/j.aohep.2019.04.014

View details for PubMedID 31164267
Pre-Operative Delta-MELD is an Independent Predictor of Higher Mortality following Liver Transplantation. Scientific reports Cholankeril, G., Li, A. A., Dennis, B. B., Gadiparthi, C., Kim, D., Toll, A. E., Maliakkal, B. J., Satapathy, S. K., Nair, S., Ahmed, A. 2019; 9 (1): 8312
Abstract

Clinical decompensation immediately prior to liver transplantation may affect post-liver transplant (LT) outcomes. Using the serial Model for End-Stage Liver Disease (MELD) scores recorded in the United Network for Organ Sharing national registry (2010-2017), we analyzed post-LT mortality among adult LT recipients based on the degree of fluctuation in MELD score during the 30-day period prior to LT surgery. Delta-MELD (D-MELD) was defined as recipient MELD score at LT minus lowest MELD score within the preceding 30 days. Impact of D-MELD as a continuous and categorical variable (D-MELD 0-4, 5-10, >10) on early, 30-day post-LT mortality was assessed. Overall, a total of 12,785 LT recipients were analyzed, of which 8,862 (67.9%) had a pre-operative D-MELD 0-4; 2,574 (20.1%) with a D-MELD 5-10; and 1,529 (12.0%) with a D-MELD > 10. One-point incremental increase in pre-operative D-MELD (adjusted HR, 1.07, 95% CI: 1.04-1.10) was associated with higher 30-day post-LT mortality. Moreover, pre-operative D-MELD > 10 was associated with nearly a two-fold increased risk for 30-day post-LT mortality (adjusted HR, 1.89, 95% CI: 1.30-2.77) compared to D-MELD 0-4. The increased risk of pre-LT mortality associated with severity of clinical decompensation assessed by the magnitude of pre-operative D-MELD persists in the early post-LT period.

View details for DOI 10.1038/s41598-019-44814-y

View details for PubMedID 31165776
Potential Mechanisms Influencing the Inverse Relationship Between Cannabis and Nonalcoholic Fatty Liver Disease: A Commentary. Nutrition and metabolic insights Dibba, P., Li, A. A., Cholankeril, G., Ali Khan, M., Kim, D., Ahmed, A. 2019; 12: 1178638819847480
Abstract

Nonalcoholic fatty liver disease (NAFLD) develops when the liver is unable to oxidize or export excess free fatty acids generated by adipose tissue lipolysis, de novo lipogenesis, or dietary intake. Although treatment has generally been centered on reversing metabolic risk factors that increase the likelihood of NAFLD by influencing lifestyle modifications, therapeutic modalities are being studied at the cellular and molecular level. The endocannabinoid system has been of recent focus. The agonism and antagonism of cannabinoid receptors play roles in biochemical mechanisms involved in the development or regression of NAFLD. Exocannabinoids and endocannabinoids, the ligands which bind cannabinoid receptors, have been studied in this regard. Exocannabinoids found in cannabis (marijuana) may have a therapeutic benefit. Our recent study demonstrated an inverse association between marijuana use and NAFLD among adults in the United States. This commentary combines knowledge on the role of the endocannabinoid system in the setting of NAFLD with the findings in our article to hypothesize different potential mechanisms that may influence the inverse relationship between cannabis and NAFLD.

View details for DOI 10.1177/1178638819847480

View details for PubMedID 31308686

View details for PubMedCentralID PMC6612909
Association between Advanced Fibrosis in Fatty Liver Disease and Overall Mortality based on Body Fat Distribution. Journal of gastroenterology and hepatology Chung, G. E., Heo, N. J., Kim, D., Kwak, M. S., Yim, J. Y., Kim, J. S., Ahmed, A. 2019
Abstract

Studies on association between fatty liver disease and overall mortality have yielded conflicting results. We evaluated the impact of fatty liver disease and advanced fibrosis on overall morality with a focus on body size and abdominal fat distribution measured by computed tomography (CT).We performed a prospective cohort study including 34,080 subjects (mean age, 51.4 years; 58.6% men) who underwent abdominal ultrasonography and fat CT, from 2007 to 2015. Fatty liver was diagnosed by ultrasonography, and advanced fibrosis was defined as high probability of advanced fibrosis based on three noninvasive methods, aspartate aminotransferase-to-platelet ratio index, nonalcoholic fatty liver disease fibrosis score, and FiB-4 score. Body size was categorized by body mass index into obese (≥25 kg/m2 ) or nonobese (<25 kg/m2 ). Multivariate proportional Cox hazard regression analyses were performed.The prevalence of fatty liver disease was 37.5%, while the prevalence of advanced fibrosis in fatty liver disease was 1.8%. During a median follow-up of 87 months (interquartile range, 62-110), 296 deaths occurred. Fatty liver disease was not associated with higher overall mortality (multivariate-adjusted hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.77-1.34), while increased subcutaneous adiposity was associated with decreased mortality (HR 0.72, 95% CI 0.60-0.88). Advanced fibrosis resulted in a 3.5-fold increase in overall mortality (adjusted HR 3.52, 95% CI, 1.86-6.65), which was more pronounced in the nonobese.While fatty liver disease did not impact overall mortality, subcutaneous adiposity was associated with reduced overall mortality. Advanced fibrosis was an independent predictor of increase in overall mortality.

View details for DOI 10.1111/jgh.14778

View details for PubMedID 31272131
Impact of sarcopenia on the progression of nonalcoholic fatty liver disease: a frequently forgotten association. Hepatobiliary surgery and nutrition Li, A. A., Ahmed, A., Kim, D. 2019; 8 (3): 260–61
View details for DOI 10.21037/hbsn.2018.12.10

View details for PubMedID 31245407

View details for PubMedCentralID PMC6561878
Treatment of inoperable hepatocellular carcinoma with immunotherapy. BMJ case reports Tighe, S. P., Iqbal, U., Fernandes, C. T., Ahmed, A. 2019; 12 (7)
Abstract

In the USA, mortality associated with hepatocellular carcinoma (HCC) continues to rise. Globally, HCC is the third most common cause of cancer-related death. In early stages of HCC, hepatic resection or liver transplantation are the preferred treatment options with a high probability of recurrence-free postoperative course. However, ineffective screening of chronic liver diseases in high-risk populations, poor linkage to care and suboptimal HCC surveillance has led to increasing rates of late-stage HCC at clinical presentation or diagnosis amenable only to palliative and experimental treatment options. Our case is a 66-year-old man with chronic hepatitis C virus infection complicated by cirrhosis and inoperable HCC which was non-responsive to selective intrahepatic trans-arterial chemoembolisation by interventional radiology. Therefore, he was treated with nivolumab immunotherapy and demonstrated normalisation of previously elevated alpha-fetoprotein levels suggestive of at least a partial response to immunotherapy. No adverse events related to nivolumab immunotherapy were encountered.

View details for DOI 10.1136/bcr-2019-229744

View details for PubMedID 31352386
Readmission Rates and Associated Outcomes for Alcoholic Hepatitis: A Nationwide Cohort Study. Digestive diseases and sciences Adejumo, A. C., Cholankeril, G., Iqbal, U., Yoo, E. R., Boursiquot, B. C., Concepcion, W. C., Kim, D., Ahmed, A. 2019
Abstract

Alcoholic hepatitis (AH) can lead to sudden and severe hepatic decompensation necessitating recurrent hospitalizations. We evaluated the trends, predictors, and healthcare cost burden of AH-related readmissions in the USA.Utilizing the National Readmissions Database 2010-2014, we performed a retrospective longitudinal analysis to identify the index readmission with AH for up to 90 days after discharge. Annual trends of 30- and 90-day AH-related readmissions were calculated. Predictors of 30- and 90-day readmission were determined by multivariate logistic regression. Annual healthcare cost burden associated with AH-linked readmissions was estimated.Of the 21,572 (unweighted: 50,769) AH-related hospitalizations, 4917 (22.8%) and 7890 (36.6%) were readmitted in 30 and 90 day, respectively, with rates that were statistically unchanged from 2010 to 2014. Predictors of 30-day readmissions included female gender, hepatitis C virus infection, cirrhosis, ascites, acute kidney injury, urinary tract infection, history of bariatric surgery, chronic pancreatitis, and high medical comorbidity index. Acute pancreatitis and palliative care consultation were associated with a lower risk of 30-day readmission. Predictors of 90-day readmission were similar to risk factors for 30-day readmission. From 2010 to 2014, the annual cost (and total hospitalization days) burden increased in 2014 to $164 million (22,244 days) and $321 million (42,772 days) for 30- and 90-day AH-related readmissions, respectively.Despite relatively stable trends in AH-related readmission, the total LOS and cost has been rising. A target-directed approach with a focus on high-risk subpopulations may help understand the unique challenges associated with the rising cost of AH-related readmissions.

View details for DOI 10.1007/s10620-019-05759-4

View details for PubMedID 31372912
Nonalcoholic Fatty Liver Disease: Epidemiology, Liver Transplantation Trends and Outcomes, and Risk of Recurrent Disease in the Graft. Journal of clinical and translational hepatology Liu, A., Galoosian, A., Kaswala, D., Li, A. A., Gadiparthi, C., Cholankeril, G., Kim, D., Ahmed, A. 2018; 6 (4): 420–24
Abstract

In parallel with the rising prevalence of metabolic syndrome globally, nonalcoholic fatty liver (NAFL) disease is the most common chronic liver disease in Western countries and nonalcoholic steatohepatitis (NASH) has become increasingly associated with hepatocellular carcinoma. Recent studies have identified NASH as the most rapidly growing indication for liver transplantation (LT). As a hepatic manifestation of the metabolic syndrome, NAFL disease can be histologically divided into NAFL and NASH. NAFL is considered a benign condition, with histological changes of hepatocyte steatosis but without evidence of hepatocellular injury or fibrosis. This is distinct from NASH, which is characterized by hepatocyte ballooning and inflammation, and which can progress to fibrosis and cirrhosis, hepatocellular carcinoma, and liver failure. As for any other end-stage liver disease, LT is a curative option for NASH after the onset of decompensated cirrhosis or hepatocellular carcinoma. Although some studies have suggested increased rates of sepsis and cardiovascular complications in the immediate postoperative period, the long-term posttransplant survival of NASH cases is similar to other indications for LT. Recurrence of NAFL following LT is common and can be challenging, although recurrence rates of NASH are lower. The persistence or progression of metabolic syndrome components after LT are likely responsible for NASH recurrence in transplanted liver. Therefore, while maintaining access to LT is important, concerted effort to address the modifiable risk factors and develop effective screening strategies to identify early stages of disease are paramount to effectively tackle this growing epidemic.

View details for PubMedID 30637220
Use of anti-platelet agents in the prevention of hepatic fibrosis in patients at risk for chronic liver disease: a systematic review and meta-analysis. Hepatology international Iqbal, U., Dennis, B. B., Li, A. A., Cholankeril, G., Kim, D., Khan, M. A., Ahmed, A. 2018
Abstract

BACKGROUND AND AIMS: While the association between platelet activation and hepatic fibrosis has been previously demonstrated in animal studies; the utility of anti-platelet agents in reversing the progression of hepatic fibrosis requires further review. Utilizing systematic review methods, we provide to our knowledge the first meta-analysis combining evidence from all studies aimed to establish the effect of anti-platelet agents in the prevention of hepatic fibrosis.METHODS: We searched Medline, EMBASE and PubMed databases from inception to October 2018 to identify all studies aimed at evaluating the role of anti-platelet agents in the prevention of hepatic fibrosis. The primary outcome was hepatic fibrosis. The initial title, abstract, and full-text screening were performed in duplicate. Risk of bias was evaluated using the Newcastle-Ottawa Scale. A fixed-effect generic inverse variance method was used to create a pooled estimate of the odds of hepatic fibrosis in patients with anti-platelet agents versus without anti-platelet agents.RESULTS: Among the 2310 unique articles identified during the title screening, 4 studies with a combined population of 3141 patients were deemed eligible for inclusion into the meta-analysis establishing the effect of anti-platelet agents on hepatic fibrosis. One study failed to report their findings in the entire cohort, electing to instead summarize the effects of anti-platelets within subgroups categorized by fibrotic risk factors. Use of anti-platelets was associated with 32% decreased odds of hepatic fibrosis, (adjusted pooled OR 0.68; CI 0.56-0.82, p≤0.0001). The statistical heterogeneity among the studies was insignificant.CONCLUSION: Use of anti-platelet agents is associated with the decreased odds of hepatic fibrosis. Due to limited evidence, future high-quality randomized controlled trials with larger comparative samples are required to further delineate the potential beneficial effects of these drugs in preventing hepatic fibrosis.

View details for PubMedID 30539518
Disparities in mortality for chronic liver disease among Asian subpopulations in the United States from 2007 to 2016 JOURNAL OF VIRAL HEPATITIS Li, A. A., Kim, D., Kim, W., Dibba, P., Wong, K., Cholankeril, G., Jacobson, I. M., Younossi, Z. M., Ahmed, A. 2018; 25 (12): 1608–16
View details for DOI 10.1111/jvh.12981

View details for Web of Science ID 000451117100023
Effects of Alcohol Consumption and Metabolic Syndrome on Mortality in Patients with Non-alcoholic and Alcohol-Related Fatty Liver Disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Younossi, Z. M., Stepanova, M., Ong, J., Yilmaz, Y., Duseja, A., Eguchi, Y., El Kassas, M., Castellanos-Fernandez, M., George, J., Jacobson, I. M., Bugianesi, E., Wai-Sun Wong, V., Arrese, M., de Ledinghen, V., Romero-Gomez, M., Mendez-Sanchez, N., Ahmed, A., Wong, R., Papatheodoridis, G., Serfaty, L., Younossi, I., Nader, F., Ziayee, M., Afendy, A., Global NASH Council 2018
Abstract

BACKGROUND & AIMS: Non-alcoholic and alcohol-related fatty liver disease are overlapping diseases in which metabolic syndrome and alcohol consumption each contribute to progressive liver disease. We aimed to assess the effects of alcohol consumption and metabolic syndrome on mortality in individuals with fatty liver.METHODS: We searched the National Health and Nutrition and Examination Survey III for adults (20-74 years old) with hepatic steatosis, detected by ultrasound, for whom mortality and follow-up data were available. We collected data from the alcohol use questionnaire (self-reported number of days a participant drank alcohol; the number of drinks [10 g alcohol] per day on a drinking day; the number of days the participant had 5 or more drinks) and calculated the average amount of alcohol consumption in drinks/day for each participant during the year preceding enrollment. Excessive alcohol consumption for men was >3 drinks/day and for women was >1.5 drinks/day. We also collected clinical data, and mortality data were obtained from the National Death Index. Demographic and clinical parameters were compared among consumption groups using the chi2 test for independence or survey regression models. We used Cox proportional hazard models to identify independent predictors of all-cause and cause-specific mortality.RESULTS: The study cohort included 4264 individuals with hepatic steatosis (mean age, 45.9 years; 51% male; 76% white; 46% with metabolic syndrome; 6.2% with excessive alcohol use). There was no significant difference in mean age between individuals with vs without excessive alcohol consumption (P=.65). However, overall mortality was significantly higher among participants with excessive alcohol consumption (32.2%) vs participants with non-excessive alcohol use (22.2%) after mean 20 years of follow up (P=.003), as well as after 5 years of follow up. In multivariate analysis, the presence of metabolic syndrome (adjusted hazard ratio [aHR], 1.43; 95% CI, 1.12-1.83) and excessive alcohol consumption (aHR, 1.79; 95% CI, 1.21-2.66) were independently associated with an increased risk of death in individuals with hepatic steatosis; any lower average amount of alcohol consumption was not associated with mortality (all P>.60). In a subgroup analysis, the association of excessive alcohol use with mortality was significant in individuals with metabolic syndrome (aHR, 2.46; 95% CI, 1.40-4.32) but not without it (P=.74).CONCLUSION: In review of data from the National Health and Nutrition and Examination Survey III, we associated alcohol consumption with increased mortality in participants with fatty liver and metabolic syndrome. These findings indicate an overlap between non-alcoholic and alcohol-related fatty liver disease.

View details for PubMedID 30476585
Low-Normal Thyroid Function is Associated with Advanced Fibrosis among Adults in the United States. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D., Yoo, E. R., Li, A. A., Fernandes, C. T., Tighe, S. P., Cholankeril, G., Hameed, B., Ahmed, A. 2018
View details for PubMedID 30458247
Early Liver Transplantation is a Viable Treatment Option in Severe Acute Alcoholic Hepatitis ALCOHOL AND ALCOHOLISM Puri, P., Cholankeril, G., Myint, T. Y., Goel, A., Sarin, S., Harper, A. M., Ahmed, A. 2018; 53 (6): 716–18
Abstract

Liver transplantation is lifesaving for patients with severe acute alcoholic hepatitis (SAH) with preliminary data demonstrating favorable early post-transplant outcomes. Using the United Network for Organ Sharing database, we demonstrate that liver transplantation for SAH in the USA has steadily increased and is associated with similar 1- and 3-year post-transplant survival as well as comparable 30-day waitlist mortality to acute liver failure due to drug-induced liver injury.

View details for PubMedID 30099535

View details for PubMedCentralID PMC6203122
Disparate Trends in Mortality of Etiology-specific Chronic Liver Disease Among Hispanic Sub-Populations. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D., Li, A. A., Perumpail, R. B., Cholankeril, G., Gonzalez, S. A., Kim, W., Ahmed, A. 2018
Abstract

BACKGROUND & AIMS: Little is known about trends in mortality among Hispanic subpopulations and etiologies of chronic liver disease (CLD). We investigated trends in mortality of CLD among the 3 largest Hispanic subgroups based on origin (Mexicans, Puerto Ricans, and Cubans) in the United States (US) from 2007 to 2016.METHODS: We collected data from the US Census and national mortality database, calculated age-standardized mortalities for CLD among Hispanic subgroups, and compared these with non-Hispanic whites. We determined mortality rate patterns by joinpoint analysis with estimates of annual percentage change.RESULTS: Hispanics were relatively younger with a lower likelihood of high school education than non-Hispanic whites at time of death. Puerto Ricans had the highest rates of age-standardized hepatitis C virus-related mortality in 2016, followed by non-Hispanic whites, Mexicans, and Cubans. Age-standardized mortality rates associated with hepatitis B virus infection decreased steadily among all subjects. Age-standardized mortality rates from alcoholic liver disease and nonalcoholic fatty liver disease among non-Hispanic whites and all Hispanics increased and accelerated. Mexicans had the highest rates of age-standardized alcoholic liver disease-related mortality, followed by non-Hispanic whites, Puerto Ricans, and Cubans. Cirrhosis- and hepatocellular carcinoma-related mortality rates increased steadily from 2007 to 2016, with the highest among Puerto Ricans and non-Hispanic whites and Mexicans, and lowest in Cubans.CONCLUSIONS: We found high levels of heterogeneity in CLD-related mortality patterns among the 3 largest Hispanic subgroups. Therefore, combining Hispanics as an aggregate group obscures potentially meaningful heterogeneity in etiology-specific CLD-related mortality rates among Hispanic subgroups.

View details for PubMedID 30391436
Liver Transplantation for HCV Non-Viremic Recipients with HCV Viremic Donors. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Kwong, A. J., Wall, A., Melcher, M., Wang, U., Ahmed, A., Subramanian, A., Kwo, P. Y. 2018
Abstract

In the context of organ shortage, the opioid epidemic, and effective direct-acting antiviral (DAA) therapy for hepatitis C (HCV), more HCV-infected donor organs may be used for liver transplantation. Current data regarding outcomes after donor-derived HCV in previously non-viremic liver transplant recipients are limited. Clinical data for adult liver transplant recipients with donor-derived HCV infection from March 2017 to January 2018 at our institution were extracted from the medical record. Ten patients received livers from donors known to be infected with HCV based on positive nucleic acid testing (NAT). Seven had a prior diagnosis of HCV and were treated before liver transplantation. All recipients were non-viremic at the time of transplantation. All 10 recipients derived hepatitis C infection from their donor and achieved sustained virologic response at 12 weeks post-treatment (SVR-12) with DAA-based regimens, with a median time from transplant to treatment initiation of 43 days (IQR 20-59). There have been no instances of graft loss or death, with median follow-up of 380 days (IQR 263-434) post-transplant. Transplantation of HCV-viremic livers into non-viremic recipients results in acceptable short-term outcomes. Such strategies may be used to expand the donor pool and increase access to liver transplantation. This article is protected by copyright. All rights reserved.

View details for PubMedID 30378723
Longitudinal trends in renal function in chronic hepatitis B patients receiving oral antiviral treatment. Alimentary pharmacology & therapeutics Udompap, P., Kim, D., Ahmed, A., Kim, W. R. 2018
Abstract

BACKGROUND: Long term renal safety of antiviral agents against hepatitis B virus (HBV) has been debated.AIM: To compare longitudinal trends of renal function among HBV mono-infected patients receiving entecavir (ETV), tenofovir disoproxil fumarate (TDF), and adefovir (ADV) in comparison to untreated subjects.METHODS: A retrospective cohort consisting of 815 patients with chronic HBV infection was constructed. Serial estimated glomerular filtration rate (eGFR) was compared to the expected rate of age-dependent decline in eGFR, derived from the National Health and Nutrition Examination Survey (NHANES) data. Generalised estimating equations and linear mixed-effects models were used to compare trends in eGFR (in mL/min/1.73m2 as a "unit").RESULTS: In NHANES data (n=23051), each year of age was associated with a 0.86 unit decrease in eGFR in subjects without hypertension and 0.96 units with hypertension. The Stanford cohort consisted of patients who received ETV (n=207), TDF (n=191), ADV (n=46) or no therapy (n=371). After a median follow-up 4.0 (interquartile range: 1.9-6.5) years, there was no significant difference in the expected and observed rates of eGFR decline in untreated HBV patients. Patients receiving antiviral treatment experienced steeper reduction in renal function than expected. In the multivariable model, ETV was associated with eGFR loss at 1.81 units per year (P=0.06, compared to untreated patients). TDF- and ADV-treated patients experienced significantly higher rate of eGFR loss at 2.21 and 2.63 units per year, respectively (both P<0.01).CONCLUSION: In this longitudinal cohort study, HBV patients receiving antiviral therapy, particularly TDF and ADV, experienced more rapid loss in eGFR.

View details for PubMedID 30370967
Association of Pre-Transplant Renal Function with Liver Graft and Patient Survival after Liver Transplantation in Patients with Nonalcoholic Steatohepatitis. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Molnar, M. Z., Joglekar, K., Jiang, Y., Cholankeril, G., Abdul, M. K., Kedia, S., Gonzalez, H. C., Ahmed, A., Singal, A., Bhamidimarri, K. R., Aithal, G. P., Duseja, A., Wong, V. W., Gulnare, A., Puri, P., Nair, S., Eason, J. D., Satapathy, S. K., Global NAFLD Consortium 2018
Abstract

BACKGROUND: Nonalcoholic Steatohepatitis(NASH) is one of the top three indications for liver transplantation in western countries. It is unknown whether renal dysfunction at the time of liver transplantation has any effect on post-liver transplantation outcomes in recipients with NASH.METHODS: From the United Network for Organ Sharing-Standard Transplant Analysis and Research(UNOS-STAR) dataset, we identified 4,088 NASH recipients who received deceased donor liver transplant. We divided our recipients a priori into three categories: Group I with estimated glomerular filtration rate (eGFR)<30 ml/min/1.73m2 at the time of LT and/or received dialysis within 2 weeks preceding LT(n=937); Group II included recipients who had eGFR≥30 ml/min/1.73m2 and did not receive renal replacement therapy prior to LT(n=2,812); and Group III included recipients who underwent SLK transplantation(n=339). We examined the association of pre-transplant renal dysfunction with death with functioning graft, all-cause mortality, and graft loss using competing risk regression and Cox proportional hazards models.RESULTS: The mean±SD age of the cohort at baseline was 58±8 years, 55% were male, 80% were Caucasian, and average exception MELD score was 24±9. The median follow-up period was 5 years (median=1,816 days, interquartile range (IQR):1,090-2,723 days). Compared to Group I recipients, Group II recipients had 19% reduced trend for risk for death with functioning graft[Sub-Hazard Ratio(SHR)(95% CI):0.81(0.64-1.02)] and similar risk for graft loss [SHR(95% CI):1.25(0.59-2.62)] while Group III recipients had similar risk for death with functioning graft[SHR(95% CI):1.23(0.96-1.57)] and graft loss [SHR(95% CI):0.18(0.02-1.37)] using adjusted competing risk regression model.CONCLUSIONS: Recipients with preserved renal function before liver transplantation showed trend toward lower risk of death with functioning graft compared to SLK recipients and those with pre-transplant severe renal dysfunction in patients with NASH. This article is protected by copyright. All rights reserved.

View details for PubMedID 30369023
Temporal Trends Associated with the Rise in Alcoholic Liver Disease Related Liver Transplantation in the United States. Transplantation Cholankeril, G., Gadiparthi, C., Yoo, E. R., Dennis, B. B., Li, A. A., Hu, M., Wong, K., Kim, D., Ahmed, A. 2018
Abstract

BACKGROUND: In the United States, alcoholic liver disease (ALD) has recently become the leading indication for liver transplantation (LT).METHODS: Using the United Network for Organ Sharing registry, we examined temporal trends in adult liver transplant waitlist registrants and recipients with chronic liver disease (CLD) due to ALD from 2007 to 2016.RESULTS: From 2007 to 2016, ALD accounted for 20.4% (18 399) of all CLD waitlist (WL) additions. The age-standardized ALD WL addition rate was 0.459 per 100 000 US population in 2007; nearly doubled to 0.872 per 100 000 US population in 2016 and increased with an average annual percent change of 47.56% (95% CI: 30.33% to 64.72%).The ALD WL addition rate increased over twofold among young (18-39 years) and middle-aged (40-59 years) adults during the study period. Young adult ALD WL additions presented with a higher severity of liver disease including Model for End-Stage Liver Disease score compared to middle aged and older adults (> 60 years). The number of annual ALD WL deaths readily rose from 2014 to 2016, despite an overall annual decline in all CLD WL deaths. Severe hepatic encephalopathy, low BMI (< 18.5) and diabetes mellitus were significant predictors for 1-year waitlist mortality.CONCLUSION: ALD-related WL registrations and LT have increased over the past decade with a disproportionate increase in young and middle-aged adults. These subpopulations within the ALD cohort need to be evaluated in future studies to improve our understanding of factors associated with these alarming trends.

View details for PubMedID 30300285
Predictors of Nonalcoholic Steatohepatitis and Significant Fibrosis in Non-Obese Nonalcoholic Fatty Liver Disease. Liver international : official journal of the International Association for the Study of the Liver Kim, D., Kim, W., Joo, S. K., Kim, J. H., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2018
Abstract

AIMS: We compared (1) demographic and clinical characteristics, and (2) determinants of nonalcoholic steatohepatitis (NASH) and significant fibrosis in non-obese and obese NAFLD.METHODS: A cross-sectional study of 664 Asian subjects (mean age 53.1 years; men 50.3%) with biopsy-proven NAFLD and controls was conducted. Subjects were divided by their body mass index (BMI) into obese (BMI ≥25 kg/m2 ) and non-obese (BMI <25 kg/m2 ).RESULTS: Observations in subjects with non-obese NAFLD were in between non-obese controls and obese NAFLD subjects for BMI, sagittal abdominal diameter (SAD), aminotransferase levels, insulin resistance, and abdominal visceral adipose tissue (VAT) area. There was no significant difference in histology between non-obese and obese subjects with NAFLD except for lower grade of hepatic steatosis in non-obese NAFLD and higher severity of hepatic fibrosis in non-obese NASH. Predictors of NASH in non-obese subjects included females (odds ratio [OR] 2.49), higher alanine aminotransferase (OR 1.03), lower high density lipoprotein-cholesterol (OR 0.96), higher prevalence of diabetes (OR 3.65) and higher VAT area (OR 1.63 per SD increase of VAT), while age (OR 1.04), higher aspartate aminotransferase (OR 1.02), diabetes (OR 2.76,), and higher VAT area (OR 1.57 per SD increase) were associated with significant fibrosis in the non-obese. SAD was independently associated with NASH or significant fibrosis among non-obese NAFLD subjects.CONCLUSION: While there were a few phenotypic differences from obese subjects, non-obese subjects with NAFLD displayed a similar severity of histological liver damage. Potential factor(s) beyond obesity may play a role as non-obese NAFLD advances to more severe disease. This article is protected by copyright. All rights reserved.

View details for PubMedID 30298568
Anti-Diabetic Medications for the Pharmacologic Management of NAFLD. Diseases (Basel, Switzerland) Cholankeril, R., Patel, V., Perumpail, B. J., Yoo, E. R., Iqbal, U., Sallam, S., Shah, N. D., Kwong, W., Kim, D., Ahmed, A. 2018; 6 (4)
Abstract

As a chronic disease encompassing a wide spectrum of liver-related histologic damage, nonalcoholic fatty liver disease (NAFLD) is becoming a global epidemic with significant impacts on all-cause morbidity and mortality. Insulin resistance and type 2 diabetes mellitus predispose individuals to NAFLD and related complications. Therefore, timely intervention with anti-diabetic medications may prevent and delay the development of NAFLD or have a therapeutic implication. The focus of this review is to evaluate the evidence supporting the efficacy of anti-diabetic medications in the treatment of NAFLD. While many of these anti-diabetic agents have shown to improve biochemical parameters, their effect on hepatic histology is limited. Among anti-diabetic medications, only thiazolidinediones and glucagon-like peptide-1 receptor agonists demonstrate significant improvement in hepatic histology.

View details for PubMedID 30282916
Improved Short-Term Survival in HCV Seropositive Kidney Transplant Recipients during the Daa Era in the United States Wong, K., Cholankeril, G., Gadiparthi, C., Somasundar, P., Busque, S., Esquivel, C. O., Ahmed, A. WILEY. 2018: 140A
View details for Web of Science ID 000446020500225
Use of Antiplatelet Agents for the Prevention of Hepatic Fibrosis: A Systematic Review and Meta-Analysis Iqbal, U., Li, A. A., Dibba, P., Yoo, E. R., Cholankeril, G., Khan, M., Kim, D., Ahmed, A. WILEY. 2018: 1141A
View details for Web of Science ID 000446020503231
Trends in Causes of Mortality in Liver Transplantation Recipients: Comparison Among Nash, ALD, and HCV Cohorts Yoo, E. R., Cholankeril, G., Li, A. A., Dibba, P., Iqbal, U., Khan, M., Gadiparthi, C., Kim, D., Ahmed, A. WILEY. 2018: 966A–967A
View details for Web of Science ID 000446020502493
Pre-Operative Magnitude in the Rise of Meld Score Is a Predictor of Survival Following Liver Transplantation Cholankeril, G., Yoo, E. R., Li, A. A., Kim, D., Ahmed, A. WILEY. 2018: 690A–691A
View details for Web of Science ID 000446020501418
Non-Alcoholic Fatty Liver Disease (NAFLD) and Alcoholic Fatty Liver Disease (AFLD): The Impact of Alcohol Consumption and Metabolic Syndrome on Mortality Younossi, Z. M., Stepanova, M., Ong, J., Yilmaz, Y., Duseja, A. K., Eguchi, Y., El Kassas, M., Fernandez, M., George, J., Jacobson, I. M., Bugianesi, E., Wong, V., Arrese, M., de Ledinghen, V., Romero-Gomez, M., Mendez-Sanchez, N., Ahmed, A., Wong, R. J., Papatheodoridis, G. V., Serfaty, L., Mathurin, P., Younossi, I., Nader, F., Ziayee, M., Afendy, A. WILEY. 2018: 801A–802A
View details for Web of Science ID 000446020502188
When to Initiate Weight Loss Medications in the NAFLD Population. Diseases (Basel, Switzerland) Yoo, E. R., Sallam, S., Perumpail, B. J., Iqbal, U., Shah, N. D., Kwong, W., Cholankeril, G., Kim, D., Ahmed, A. 2018; 6 (4)
Abstract

Nonalcoholic fatty liver disease (NAFLD) is characterized by histological evidence of hepatic steatosis, lobular inflammation, ballooning degeneration and hepatic fibrosis in the absence of significant alcohol use and other known causes of chronic liver diseases. NAFLD is subdivided into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). NAFL is generally benign but can progress to NASH, which carries a higher risk of adverse outcomes including cirrhosis, end-stage liver disease, hepatocellular carcinoma and death if liver transplantation is not pursued in a timely fashion. Currently, lifestyle modifications including healthy diet and increased physical activity/exercise culminating in weight loss of 5% to >10% is the cornerstone of treatment intervention for patients with NAFLD. Patients with NAFLD who fail to obtain this goal despite the help of dietitians and regimented exercise programs are left in a purgatory state and remain at risk of developing NASH-related advance fibrosis. For such patients with NAFLD who are overweight and obese, healthcare providers should consider a trial of FDA-approved anti-obesity medications as adjunct therapy to provide further preventative and therapeutic options as an effort to reduce the risk of NAFLD-related disease progression.

View details for PubMedID 30274326
Increasing Trends in Transplantation of HCV-positive Livers into Uninfected Recipients. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Cholankeril, G., Li, A. A., Dennis, B. B., Toll, A. E., Kim, D., Bonham, C. A., Nair, S., Ahmed, A. 2018
View details for PubMedID 30268562
The Role of Vitamin E in the Treatment of NAFLD. Diseases (Basel, Switzerland) Perumpail, B. J., Li, A. A., John, N., Sallam, S., Shah, N. D., Kwong, W., Cholankeril, G., Kim, D., Ahmed, A. 2018; 6 (4)
Abstract

There has been a growing interest in the role of vitamin E supplementation in the treatment and/or prevention of nonalcoholic fatty liver (NAFLD). We performed a systematic review of the medical literature from inception through 15 June 2018 by utilizing PubMed and searching for key terms such as NAFLD, vitamin E, alpha-tocopherol, and nonalcoholic steatohepatitis (NASH). Data from studies and medical literature focusing on the role of vitamin E therapy in patients with NAFLD and nonalcoholic steatohepatitis (NASH) were reviewed. Most studies assessing the impact of vitamin E in NAFLD were designed to evaluate patients with NASH with documented biochemical and histological abnormalities. These studies demonstrated improvement in biochemical profiles, with a decline in or normalization of liver enzymes. Furthermore, histological assessment showed favorable outcomes in lobular inflammation and hepatic steatosis following treatment with vitamin E. Current guidelines regarding the use of vitamin E in the setting of NAFLD recommend that vitamin E-based treatment be restricted to biopsy-proven nondiabetic patients with NASH only. However, some concerns have been raised regarding the use of vitamin E in patients with NASH due to its adverse effects profile and lack of significant improvement in hepatic fibrosis. In conclusion, the antioxidant, anti-inflammatory, and anti-apoptotic properties of vitamin E accompanied by ease-of-use and exceptional tolerability have made vitamin E a pragmatic therapeutic choice in non-diabetic patients with histologic evidence of NASH. Future clinical trials with study design to assess vitamin E in combination with other anti-fibrotic agents may yield an additive or synergistic therapeutic effect.

View details for PubMedID 30249972
Disparities in Mortality for Chronic Liver Disease among Asian Sub-Populations in the United States from 2007 to 2016. Journal of viral hepatitis Li, A. A., Kim, D., Kim, W., Dibba, P., Wong, K., Cholankeril, G., Jacobson, I. M., Younossi, Z. M., Ahmed, A. 2018
Abstract

The Asian-American population is characterized by remarkable diversity. Studying Asians as an aggregate group may obscure clinically-meaningful heterogeneity. We performed a population-based study using data from the United States (US) National Vital Statistics System. We determined the trends in age-standardized mortality rates for chronic liver disease stratified by etiology among the most populous US-based Asian subgroups (Asian Indians, Chinese, Filipino, Japanese, Korean, and Vietnamese) and compared it to non-Hispanic whites. Annual percentage change was calculated to determine temporal mortality patterns using joinpoint analysis.Hepatitis C virus-related mortality rates were higher in non-Hispanic whites compared to individual Asian subgroups, but a sharp decline in mortality rates was noted in 2014 among non-Hispanic whites and all Asian subgroups. Age-standardized hepatitis B virus-related mortality rates were higher in all Asian subgroups as compared to non-Hispanic whites in 2016, with the highest mortality among Vietnamese followed by Chinese. Mortality rates for alcoholic liver disease have been steadily trending upwards in all Asian subgroups, with the highest mortality in Japanese. Overall, age-standardized cirrhosis-related mortality rates were highest in non-Hispanic whites, followed by Japanese, and more distantly by Vietnamese and other subgroups. However, hepatocellular carcinoma-related mortality rates were higher in most Asian subgroups led by Vietnamese, Japanese and Koreans compared to non-Hispanic whites. In this population-based study utilizing a nationally representative database, we demonstrated a marked heterogeneity in the mortality rates of etiology-specific chronic liver disease among Asian subgroups in the US. This article is protected by copyright. All rights reserved.

View details for PubMedID 30112849
Continuous Positive Airway Pressure Therapy on Nonalcoholic Fatty Liver Disease in Patients With Obstructive Sleep Apnea. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine Kim, D., Ahmed, A., Kushida, C. 2018; 14 (8): 1315–22
Abstract

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with nonalcoholic fatty liver disease (NAFLD) and related advanced fibrosis. We studied the treatment of OSA with continuous positive airway pressure (CPAP) in a population with NAFLD.METHODS: Using an institutional database (2010-2014), we identified patients with NAFLD and OSA and studied changes in serum aminotransferases before and after CPAP use. We defined suspected NAFLD (sNAFLD) as serum alanine aminotransferase (ALT) > 30 U/L for men and > 19 U/L for women in the absence of known causes of chronic liver disease. The aspartate aminotransferase (AST) to platelet ratio index (APRI) was used to determine significant fibrosis. Consistent CPAP use for more than 3 months with adequate adherence parameters defined good adherence.RESULTS: Of 351 patients with OSA on CPAP treatment, majority (mean age 57.6 years, 59.3% male) had abnormal ALT, and 89.4% met the criteria for sNAFLD. The prevalence of sNAFLD was higher among patients with moderate to severe OSA (90.6%) versus mild OSA (86.3%). There was a statistically significant improvement in AST, ALT, and APRI with CPAP therapy (all P < .01). There was an apparent dose-response relationship: patients with good adherence to CPAP showed a significantly larger decrease in AST and ALT than did those with poor adherence (P < .01). Multivariable logistic regression analysis showed CPAP treatment with adequate adherence (odds ratio = 3.93, 95% confidence interval = 1.29-11.94) was an independent predictor of regression of sNAFLD after adjusting for obesity class and severity of OSA.CONCLUSIONS: OSA treatment with CPAP was associated with significant biochemical improvement and reduction in NAFLD-related fibrosis.

View details for PubMedID 30092894
Association between cagA negative Helicobacter pylori status and nonalcoholic fatty liver disease among adults in the United States PLOS ONE Kang, S., Kim, H., Kim, D., Ahmed, A. 2018; 13 (8): e0202325
Abstract

We investigated the relationship of H. pylori stratified by cytotoxin-associated gene A (cagA) status with nonalcoholic fatty liver disease (NAFLD) in the general population of the United States (US). We utilized the Third National Health and Nutrition Examination Survey from 1988 to 1994 in this study. NAFLD was defined by ultrasonographic detection of hepatic steatosis in the absence of other known causes of liver diseases and significant alcohol consumption. Hepatic steatosis was assessed by parenchymal brightness, liver to kidney contrast, deep beam attenuation, bright vessel walls and gallbladder wall definition. Antibodies to H. pylori and cagA of participants were measured using H. pylori IgG and anti-cagA IgG enzyme-linked immunosorbent assays. Among 5,404 participants, the prevalence of NAFLD was higher in H. pylori positive subjects (33.5±1.8%) compared to H. pylori negative subjects (26.1±1.7%, p <0.001). In terms of cagA protein status stratification, while cagA positive H. pylori group did not demonstrate an association with NAFLD (OR: 1.05; 95% CI: 0.81-1.37), cagA negative H. pylori group was noted to have a significant association with NAFLD in a multivariable analysis (OR: 1.30; 95% CI: 1.01-1.67). In conclusion, our study demonstrated that cagA negative H. pylori infection was an independent predictor of NAFLD in the US general population.

View details for PubMedID 30110395
Changing Trends in Etiology- and Ethnicity-Based Annual Mortality Rates of Cirrhosis and Hepatocellular Carcinoma in the United States. Hepatology (Baltimore, Md.) Kim, D., Li, A. A., Perumpail, B. J., Gadiparthi, C., Kim, W., Cholankeril, G., Glenn, J. S., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2018
Abstract

With recent improvements in the treatment of end-stage liver disease (ESLD), a better understanding of the burden of cirrhosis and hepatocellular carcinoma (HCC) is needed in the United States (US). A population-based study using the US Census and national mortality database was performed. We identified the age-standardized etiology-specific mortality rates for cirrhosis and HCC among US adults aged ≥ 20 years from 2007 to 2016. We determined temporal mortality rate patterns by joinpoint analysis with estimates of annual percentage change (APC). Age-standardized cirrhosis-related mortality rates increased from 19.77/100,000 persons in 2007 to 23.67 in 2016 with an annual increase of 2.3% (95% CI 2.0-2.7). The APC in mortality rates for hepatitis C virus (HCV)-cirrhosis shifted from a 2.9% increase per year during 2007-2014 to a 6.5% decline per year during 2014-2016. Meanwhile, mortality for cirrhosis from alcoholic liver disease (ALD, APC 4.5%) and nonalcoholic fatty liver disease (NAFLD, APC 15.4%) increased over the same period, while mortality for hepatitis B virus (HBV)-cirrhosis decreased with an average APC of -1.1%. HCC-related mortality increased from 3.48/100,000 persons in 2007 to 4.41 in 2016 at an annual rate of 2.0% (95% CI 1.3-2.6). Etiology-specific mortality rates of HCC were largely consistent with cirrhosis-related mortality. Minority populations had a higher burden of HCC-related mortality.CONCLUSION: Cirrhosis- and HCC-related mortality rates increased between 2007 and 2016 in the US. However, mortality rates in HCV-cirrhosis demonstrated a significant decline from 2014-2016, during the direct-acting antiviral era. Mortality rates for ALD/NAFLD-cirrhosis and HCC have continued to increase, while HBV-cirrhosis-related mortality declined during the 10-year period. Importantly, minorities had a disproportionately higher burden of ESLD-related mortality. This article is protected by copyright. All rights reserved.

View details for PubMedID 30014489
Changing Trends in Etiology-based Annual Mortality From Chronic Liver Disease, From 2007 Through 2016. Gastroenterology Kim, D., Li, A. A., Gadiparthi, C., Khan, M. A., Cholankeril, G., Glenn, J. S., Ahmed, A. 2018
Abstract

BACKGROUND & AIMS: Although treatment of hepatitis C virus (HCV) infection has improved, the prevalence of alcoholic liver disease (ALD) has been increasing, so we need an updated estimate of the burden and etiology-specific mortality of chronic liver diseases. We studied the trends in age-standardized mortality of chronic liver diseases among adults 20 years or older in the United States (US), from 2007 through 2016.METHODS: We collected data from the US Census and National Center for Health Statistics mortality records, identifying individuals with HCV infection, ALD, nonalcoholic fatty liver disease (NAFLD), or hepatitis B virus (HBV) infection using ICD-10 codes. We obtained temporal mortality rate patterns using joinpoint trend analysis with estimates of annual percentage change (APC).RESULTS: Age-standardized HCV-related mortality increased from 7.17/100,000 persons in 2007 to 8.14/100,000 persons in 2013, followed by a marked decrease in the time period at which patients began receiving treatment with direct-acting antiviral agents (from 8.09/100,000 persons in 2014 to 7.15/100,000 persons in 2016). The APC in HCV mortality increased 2.0%/year from 2007 through 2014, but decreased 6.4%/year from 2014 through 2016. In contrast, age-standardized mortality increased for ALD (APC of 2.3% from 2007 through 2013 and APC of 5.5% from 2013 through 2016) and NAFLD (APC of 6.1% from 2007 through 2013 and APC of 11.3% from 2013 through 2016). HBV-related mortality decreased steadily from 2007 through 2016, with an average APC of -2.1% (95% CI, -3.0 to -1.2). Etiology-based mortality in minority populations were higher. HCV-related mortality (per 100,000 persons) was highest among non-Hispanic blacks (10.28) and whites (6.92), followed by Hispanics (5.94), and lowest among non-Hispanic Asians (2.33). Non-Hispanic Asians had higher mortality for HBV infection (2.82 per 100,000 vs 1.02 for non-Hispanic blacks, and 0.47 for non-Hispanic whites).CONCLUSION: In our population-based analysis of chronic liver disease mortality in the US, the decline in HCV-related mortality coincided with the introduction of direct-acting antiviral therapies, while the mortality from ALD and NAFLD increased during the same period. Minorities in the US have disproportionately higher chronic liver disease-related mortality.

View details for PubMedID 30009816
Underutilization of Hepatitis C Virus Seropositive Donor Kidneys in the United States in the Current Opioid Epidemic and Direct-Acting Antiviral Era. Diseases (Basel, Switzerland) Li, A. A., Cholankeril, G., Cheng, X. S., Tan, J. C., Kim, D., Toll, A. E., Nair, S., Ahmed, A. 2018; 6 (3)
Abstract

In recent years, the opioid epidemic and new hepatitis C virus (HCV) treatments have changed the landscape of organ procurement and allocation. We studied national trends in solid organ transplantation (2000⁻2016), focusing on graft utilization from HCV seropositive deceased donors in the pre-2014 (2000⁻2013) versus current (2014⁻2016) eras with a retrospective analysis of the United Network for Organ Sharing database. During the study period, HCV seropositive donors increased from 181 to 661 donors/year. The rate of HCV seropositive donor transplants doubled from 2014 to 2016. Heart and lung transplantation data were too few to analyze. A higher number of HCV seropositive livers were transplanted into HCV seropositive recipients during the current era: 374 versus 124 liver transplants/year. Utilization rates for liver transplantation reached parity between HCV seropositive and non-HCV donors. While the number of HCV seropositive kidneys transplanted to HCV seropositive recipients increased from 165.4 to 334.7 kidneys/year from the pre-2014 era to the current era, utilization rates for kidneys remained lower in HCV seropositive than in non-HCV donors. In conclusion, relative underutilization of kidneys from HCV seropositive versus non-HCV donors has persisted, in contrast to trends in liver transplantation.

View details for PubMedID 29996536
Waitlist Outcomes in Liver Transplant Candidates with High MELD and Severe Hepatic Encephalopathy DIGESTIVE DISEASES AND SCIENCES Gadiparthi, C., Cholankeril, G., Yoo, E. R., Hu, M., Wong, R. J., Ahmed, A. 2018; 63 (6): 1647–53
Abstract

Organ Procurement and Transplantation Network and United Network for Organ Sharing (OPTN/UNOS) implemented the Share 35 policy in June 2013 to prioritize the sickest patients awaiting liver transplantation (LT). However, Model for End-Stage Liver Disease (MELD) score does not incorporate hepatic encephalopathy (HE), an independent predictor of waitlist mortality.To evaluate the impact of severe HE (grade 3-4) on waitlist outcomes in MELD ≥ 30 patients.Using the OPTN/UNOS database, we evaluated LT waitlist registrants from 2005-2014. Demographics, comorbidities, and waitlist survival were compared between four cohorts: MELD 30-34 with severe HE, MELD 30-34 without severe HE, MELD ≥ 35 with severe HE, and MELD ≥ 35 without severe HE.Among 10,003 waitlist registrants studied, 41.6% had MELD score 30-34 and 58.4% had MELD ≥ 35. Patients with severe HE had a higher 90-day waitlist mortality in both MELD 30-34 (severe HE 71.1% vs. no HE 56.6%; p < 0.001) and MELD ≥ 35 subgroups (severe HE 85% versus no HE 74.2%; p < 0.001). MELD 30-34 patients with severe HE had similar 90-day waitlist mortality as MELD ≥ 35 patients without severe HE (71.1 vs. 74.2%, respectively; p = 0.35). On multivariate Cox proportional hazards modeling, MELD ≥ 30 patients had 58% greater risk of 90-day waitlist mortality than those without severe HE (HR 1.58, 95% CI 1.53-1.62; p < 0.001).Patients awaiting LT with MELD score of 30-34 and severe HE should receive priority status for organ allocation with exception MELD ≥ 35.

View details for PubMedID 29611079
Leukocyte Telomere Shortening Is Associated With Nonalcoholic Fatty Liver Disease-Related Advanced Fibrosis. Liver international : official journal of the International Association for the Study of the Liver Kim, D., Li, A. A., Ahmed, A. 2018
Abstract

BACKGROUND AND AIM: Telomere length and telomerase has been linked with cirrhosis and hepatocellular carcinoma. However, the impact of telomere length on nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis is in a large national population sample is not well understood.METHODS: Cross-sectional data from the National Health and Nutrition Examination Survey 1999-2002 were utilized. Suspected NAFLD was diagnosed if serum alanine aminotransferase was > 30 IU/L for men and > 19 IU/L for women in the absence of other causes of chronic liver disease. Presence of advanced fibrosis was determined by the NAFLD fibrosis score, aspartate aminotransferase to platelet ratio index, and FIB-4 score.RESULTS: Of the 6,738 participants (mean age 46.3 years, 48.4% male), suspected NAFLD prevalence was inversely associated with leukocyte telomere length in young adults aged 20-39 years, though this was not seen in the overall population. Percentage of participants with advanced fibrosis increased corresponding with leukocyte telomere length (longest to shortest). The shortest quartile of leukocyte telomere length was associated with a significantly higher odds ratio (95% confidence interval) of advanced fibrosis of 2.36 (1.32-4.24) in a univariate model compared to the longest quartile, and 2.01 (1.13-3.58) in a multivariate model adjusted for age, gender, ethnicity, waist circumference, smoking, diabetes, hypertension, total cholesterol, and high-density lipoprotein cholesterol (P for trend < 0.05, respectively).CONCLUSIONS: In this large nationally-representative sample of American adults, leukocyte telomere shortening was associated with increased risk of advanced fibrosis in the setting of suspected NAFLD independent of other known risk factors. This article is protected by copyright. All rights reserved.

View details for PubMedID 29797393
Case Report of Isoniazid-Related Acute Liver Failure Requiring Liver Transplantation. Diseases (Basel, Switzerland) Li, A. A., Dibba, P., Cholankeril, G., Kim, D., Ahmed, A. 2018; 6 (2)
Abstract

The prevalence of latent tuberculosis infection (LTBI) in the United States in 2011 and 2012 was estimated at 4.4⁻4.8%. As of 2015, 12.4 million people still possessed LTBI. Isoniazid, or isonicotinic acid hydrazine (INH), is the most commonly used medication among varying regimens that exist in the treatment of tuberculosis and LTBI. INH-related hepatotoxicity is a well-known adverse effect of its use, often causing asymptomatic elevations in serum aminotransferase levels. These elevations are typically transient and reversible, but can cause acute, clinically-significant liver injury in rare cases. We report a case of a 67-year old male who developed subacute hepatic injury secondary to INH treatment for LTBI, and ultimately underwent liver transplantation due to the progression to hepatic decompensation, despite withdrawal of the medication. Because symptoms of INH hepatotoxicity are nonspecific and prognosis can be variable, clinicians must maintain a high index of suspicion for this adverse effect. As exemplified by this case, early recognition may be life-saving.

View details for PubMedID 29783726
Impact of Drug Overdose Deaths on Solid Organ Transplantation in the United States. Journal of general internal medicine Cholankeril, G., Li, A. A., Cholankeril, R., Toll, A. E., Glenn, J. S., Ahmed, A. 2018
View details for PubMedID 29766381
Hepatitis C in Pregnancy. Diseases (Basel, Switzerland) Dibba, P., Cholankeril, R., Li, A. A., Patel, M., Fayek, M., Dibble, C., Okpara, N., Hines, A., Ahmed, A. 2018; 6 (2)
Abstract

The prevalence of hepatitis C in pregnancy is as high as 3.6% in large cohorts. The prevalence of hepatitis C acquired by vertical transmission is 0.2% to 0.4% in the United States and Europe. Although screening is not recommended in the absence of certain risk factors, the importance of understanding hepatitis C in pregnancy lies in its association with adverse maternal and neonatal outcomes. There is potential for those infants infected by vertical transmission to develop chronic hepatitis C, cirrhosis or hepatocellular carcinoma. The risk of vertical transmission is increased when mothers are co-infected with Human Immunodeficiency Virus (HIV) or possess a high viral load. There is no clear data supporting that mode of delivery increases or reduces risk. Breastfeeding is not associated with increased risk of transmission. Premature rupture of membranes, invasive procedures (such as amniocentesis), intrapartum events, or fetal scalp monitoring may increase risk of transmission. In pregnant patients, hepatitis C is diagnosed with a positive ELISA-3 and detectable Hepatitis C Virus (HCV) RNA viral load. Infants born to HCV-infected mothers should be tested for either HCV RNA on at least two separate occasions. Although prevention is not possible, there may be a role for newer direct acting anti-viral medications in the future.

View details for PubMedID 29702563
Expanding Donor Pool for Liver Transplantation by Utilizing Hepatitis C Virus-Infected Donors for Uninfected Recipients. Hepatology (Baltimore, Md.) Cholankeril, G., Gadiparthi, C., Kim, D., Ahmed, A. 2018
View details for PubMedID 29672899
Non-alcoholic Fatty Liver Disease: A Review of Anti-diabetic Pharmacologic Therapies JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY Snyder, H. S., Sakaan, S. A., March, K. L., Siddique, O., Cholankeril, R., Cummings, C. D., Gadiparthi, C., Satapathy, S. K., Ahmed, A., Cholankeril, G. 2018; 6 (2): 168–74
Abstract

Non-alcoholic fatty liver disease (NAFLD), the most common cause of liver disease, affects approximately 75 to 100 million Americans. Patients with concurrent NAFLD and type 2 diabetes mellitus have a higher risk of progressing to advanced fibrosis and non-alcoholic steatohepatitis compared to non-diabetics. Lifestyle modifications, including weight loss, remain the mainstay of treatment for NAFLD, as there are no medications currently indicated for this disease state. Anti-diabetic pharmacologic therapies aimed at improving insulin sensitivity and decreasing insulin production have been studied to determine their potential role in slowing the progression of NAFLD. In this review, we focus on the evidence surrounding anti-diabetic medications and their ability to improve disease progression in patients with NAFLD.

View details for PubMedID 29951362

View details for PubMedCentralID PMC6018310
Increased Waitlist Mortality and Lower Rate for Liver Transplantation in Hispanic Patients With Primary Biliary Cholangitis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Cholankeril, G., Gonzalez, H. C., Satapathy, S., Gonzalez, S. A., Hu, M., Khan, M. A., Yoo, E. R., Li, A. A., Kim, D., Nair, S., Wong, R. J., Kwo, P. Y., Harrison, S. A., Younossi, Z. M., Lindor, K. D., Ahmed, A. 2018
Abstract

BACKGROUND & AIMS: Data on the differences in ethnicity and race among patients with primary biliary cholangitis (PBC) awaiting liver transplantation (LT) are limited. We evaluated liver transplant waitlist trends and outcomes based on ethnicity and race in patients with PBC in the United States.METHODS: Using the United Network for Organ Sharing (UNOS) registry, we collected data on patients with PBC on the liver transplant waitlist, and performed analysis with a focus on ethnicity and race-based variations clinical manifestations, waitlist mortality and LT rates from 2000 to 2014. Outcomes were adjusted for demographics, complications of portal hypertension, and Model for End-stage Liver Disease score at time of waitlist registration.RESULTS: Although the number of white PBC waitlist registrants and additions decreased from 2000 to 2014, there were no significant changes in the number of Hispanic PBC waitlist registrants and additions each year. The proportion of Hispanic patients with PBC on the liver transplant waitlist increased from 10.7% in 2000 to 19.3% in 2014. Hispanics had the highest percentage of waitlist deaths (20.8%) of any ethnicity or race evaluated. After adjusting for demographic and clinical characteristics, Hispanic patients with PBC had the lowest overall rate for undergoing LT (adjusted hazard ratio, 0.71; 95% CI, 0. 60-0.83; P < .001) and a significantly higher risk of death while on the waitlist, compared to whites (adjusted hazard ratio, 1.41; 95% CI, 1.15-1.74; P < .001). Furthermore, Hispanic patients with PBC had the highest proportion of waitlist removals due to clinical deterioration.CONCLUSIONS: In an analysis of data from UNOS registry focusing on outcomes, we observed differences in rates of LT and liver transplant waitlist mortality of Hispanic patients compared with white patients with PBC. Further studies are needed to improve our understanding of ethnicity and race-based differences in progression of PBC.

View details for PubMedID 29427734
Use of direct-acting antiviral agents in hepatitis C virus-infected liver transplant candidates WORLD JOURNAL OF GASTROENTEROLOGY Gadiparthi, C., Cholankeril, G., Perumpail, B. J., Yoo, E. R., Satapathy, S. K., Nair, S., Ahmed, A. 2018; 24 (3): 315–22
Abstract

Since the advent of direct acting antiviral (DAA) agents, chronic hepatitis C virus (HCV) treatment has evolved at a rapid pace. In contrast to prior regimen involving ribavirin and pegylated interferon, these newer agents are highly effective, well-tolerated, have shorter course of therapy and safer essentially in all HCV patients including those with advanced liver disease and following liver transplantation. Clinicians caring for HCV-infected patients on the liver transplant (LT) waitlist are often faced with a dilemma whether to treat HCV infection before or after liver transplantation. Sustained virological response (SVR) rates following HCV treatment may improve hepatic function sufficiently enough to negate the need for LT in certain patients. On the other hand, the decrease in MELD without improvement in quality of life in certain patients may lead to delay or dropout from potentially curative LT surgery list. In this context, our review focuses on the approach to and optimal timing of DAA-based treatment of HCV infection in LT candidates in the peri-transplant period.

View details for PubMedID 29391754

View details for PubMedCentralID PMC5776393
Marijuana is not associated with progression of hepatic fibrosis in liver disease: a systematic review and meta-analysis. European journal of gastroenterology & hepatology Farooqui, M. T., Khan, M. A., Cholankeril, G., Khan, Z., Mohammed Abdul, M. K., Li, A. A., Shah, N., Wu, L., Haq, K., Solanki, S., Kim, D., Ahmed, A. 2018
Abstract

An estimated 22 million adults use marijuana in the USA. The role of marijuana in the progression of hepatic fibrosis remains unclear.We carried out a systematic review and meta-analysis to evaluate the impact of marijuana on prevalence and progression of hepatic fibrosis in chronic liver disease.We searched several databases from inception through 10 November 2017 to identify studies evaluating the role of marijuana in chronic liver disease. Our main outcome of interest was prevalence/progression of hepatic fibrosis. Adjusted odds ratios (ORs) and hazards ratios (HRs) were pooled and analyzed using random-effects model.Nine studies with 5 976 026 patients were included in this meta-analysis. Prevalence of hepatic fibrosis was evaluated in nonalcoholic fatty liver disease (NAFLD), hepatitis C virus (HCV), and hepatitis C and HIV coinfection by two, four, and one studies. Progression of hepatic fibrosis was evaluated by two studies. Pooled OR for prevalence of fibrosis was 0.91 (0.72-1.15), I=75%. On subgroup analysis, pooled OR among NAFLD patients was 0.80 (0.75-0.86), I=0% and pooled OR among HCV patients was 1.96 (0.78-4.92), I=77%. Among studies evaluating HR, pooled HR for progression of fibrosis in HCV-HIV co-infected patients was 1.03 (0.96-1.11), I=0%.Marijuana use did not increase the prevalence or progression of hepatic fibrosis in HCV and HCV-HIV-coinfected patients. On the contrary, we noted a reduction in the prevalence of NAFLD in marijuana users. Future studies are needed to further understand the therapeutic impact of cannabidiol-based formulations in the management of NAFLD.

View details for PubMedID 30234644
Serum testosterone and non-alcoholic fatty liver disease in men and women in the US. Liver international : official journal of the International Association for the Study of the Liver Yim, J. Y., Kim, J., Kim, D., Ahmed, A. 2018
Abstract

Testosterone plays a role in predisposing individuals to cardiovascular and metabolic diseases, but its effects differ between men and women. We investigated the association between serum total testosterone and non-alcoholic fatty liver disease in adults in the US.A cross-sectional analysis of data from participants in the 2011-2012 National Health and Nutrition Examination Survey was performed. Subjects with significant alcohol consumption and those with viral hepatitis were excluded. We used the highest sex-specific quartiles of serum total testosterone as references. Suspected non-alcoholic fatty liver disease was diagnosed when serum alanine aminotransferase was >30 IU/L for men and >19 IU/L for women.Of the 4758 subjects (49.4% men), the prevalence of suspected non-alcoholic fatty liver disease was inversely correlated with the sex-specific quartiles of testosterone in men and women. In a multivariate model, low total testosterone levels were associated with progressively higher odds of suspected non-alcoholic fatty liver disease in men after adjusting for age, obesity and other metabolic risk factors (P values for trends <.01). When the women were divided into 2 groups according to menopausal status, a significant correlation was observed only in the post-menopausal women (P values for trends <.01). The adjusted odds ratios for suspected non-alcoholic fatty liver disease were 1.72-1.99 in men and 2.15-2.26 in post-menopausal women (lowest quartile vs highest quartile).In this nationally representative sample of adults in the US, low total testosterone levels were associated with suspected non-alcoholic fatty liver disease in men and post-menopausal women independent of known risk factors.

View details for PubMedID 29517842
Clinical utility of ledipasvir/sofosbuvir in the treatment of adolescents and children with hepatitis C. Adolescent health, medicine and therapeutics Yang, C. H., Goel, A., Ahmed, A. 2018; 9: 103–10
Abstract

Chronic infection with hepatitis C virus (HCV) affects an estimated 0.1%-2% of the pediatric population in the United States. While the clinical course in young children is indolent, adolescents who contract HCV have a disease course similar to adults, with a 26-fold increased risk of chronic liver disease-associated mortality, hepatocellular carcinoma, and need for curative liver transplantation. Furthermore, adolescent patients are entering childbearing age and carry a risk of passing HCV to their offspring via vertical transmission. Pegylated-interferon (PEG-IFN) with ribavirin was previously the only treatment option for pediatric patients with chronic hepatitis C (CHC), but the high likelihood of adverse reactions and subcutaneous route of administration limited its use and efficacy. Recently, the direct-acting antivirals (DAAs) ledipasvir (LDV) and sofosbuvir (SOF) were approved for adolescents with CHC. This review discusses the natural history of CHC in pediatric patients, data supporting LDV/SOF in adolescents, and ongoing studies evaluating DAAs in pediatric patients.

View details for PubMedID 30104913
Mechanistic Potential and Therapeutic Implications of Cannabinoids in Nonalcoholic Fatty Liver Disease. Medicines (Basel, Switzerland) Dibba, P., Li, A., Cholankeril, G., Iqbal, U., Gadiparthi, C., Khan, M. A., Kim, D., Ahmed, A. 2018; 5 (2)
Abstract

Nonalcoholic fatty liver disease (NAFLD) is comprised of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). It is defined by histologic or radiographic evidence of steatosis in the absence of alternative etiologies, including significant alcohol consumption, steatogenic medication use, or hereditary disorders. NAFLD is now the most common liver disease, and when NASH is present it can progress to fibrosis and hepatocellular carcinoma. Different mechanisms have been identified as contributors to the physiology of NAFLD; insulin resistance and related metabolic derangements have been the hallmark of physiology associated with NAFLD. The mainstay of treatment has classically involved lifestyle modifications focused on the reduction of insulin resistance. However, emerging evidence suggests that the endocannabinoid system and its associated cannabinoid receptors and ligands have mechanistic and therapeutic implications in metabolic derangements and specifically in NAFLD. Cannabinoid receptor 1 antagonism has demonstrated promising effects with increased resistance to hepatic steatosis, reversal of hepatic steatosis, and improvements in glycemic control, insulin resistance, and dyslipidemia. Literature regarding the role of cannabinoid receptor 2 in NAFLD is controversial. Exocannabinoids and endocannabinoids have demonstrated some therapeutic impact on metabolic derangements associated with NAFLD, although literature regarding direct therapeutic use in NAFLD is limited. Nonetheless, the properties of the endocannabinoid system, its receptors, substrates, and ligands remain a significant arena warranting further research, with potential for a pharmacologic intervention for a disease with an anticipated increase in economic and clinical burden.

View details for PubMedID 29843404
The Role of Cannabinoids in the Setting of Cirrhosis. Medicines (Basel, Switzerland) Dibba, P., Li, A. A., Cholankeril, G., Iqbal, U., Gadiparthi, C., Khan, M. A., Kim, D., Ahmed, A. 2018; 5 (2)
Abstract

Although the mortality rates of cirrhosis are underestimated, its socioeconomic burden has demonstrated a significant global impact. Cirrhosis is defined by the disruption of normal liver architecture after years of chronic insult by different etiologies. Treatment modalities are recommended primarily in decompensated cirrhosis and specifically tailored to the different manifestations of hepatic decompensation. Antifibrogenic therapies are within an active area of investigation. The endocannabinoid system has been shown to play a role in liver disease, and cirrhosis specifically, with intriguing possible therapeutic benefits. The endocannabinoid system comprises cannabinoid receptors 1 (CB1) and cannabinoid receptor 2 (CB2) and their ligands, endocannabinoids and exocannabinoids. CB1 activation enhances fibrogenesis, whereas CB2 activation counteracts progression to fibrosis. Conversely, deletion of CB1 is associated with an improvement of hepatic fibrosis and steatosis, and deletion of CB2 results in increased collagen deposition, steatosis, and enhanced inflammation. CB1 antagonism has also demonstrated vascular effects in patients with cirrhosis, causing an increase in arterial pressure and vascular resistance as well as a decrease in mesenteric blood flow and portal pressure, thereby preventing ascites. In mice with hepatic encephalopathy, CB1 blockade and activation of CB2 demonstrated improved neurologic score and cognitive function. Endocannabinoids, themselves also have mechanistic roles in cirrhosis. Arachidonoyl ethanolamide (AEA) exhibits antifibrogenic properties by inhibition of HSC proliferation and induction of necrotic death. AEA induces mesenteric vasodilation and hypotension via CB1 induction. 2-arachidonoyl glycerol (2-AG) is a fibrogenic mediator independent of CB receptors, but in higher doses induces apoptosis of HSCs, which may actually show antifibrotic properties. 2-AG has also demonstrated growth-inhibitory and cytotoxic effects. The exocannabinoid, THC, suppresses proliferation of hepatic myofibroblasts and stellate cells and induces apoptosis, which may reveal antifibrotic and hepatoprotective mechanisms. Thus, several components of the endocannabinoid system have therapeutic potential in cirrhosis.

View details for PubMedID 29890719
Potential Therapeutic Benefits of Herbs and Supplements in Patients with NAFLD. Diseases (Basel, Switzerland) Perumpail, B. J., Li, A. A., Iqbal, U., Sallam, S., Shah, N. D., Kwong, W., Cholankeril, G., Kim, D., Ahmed, A. 2018; 6 (3)
Abstract

Our aim is to review the efficacy of various herbs and supplements as a possible therapeutic option in the treatment and/or prevention of nonalcoholic fatty liver disease (NAFLD). We performed a systematic review of medical literature using the PubMed Database by searching the chemical names of many common herbs and supplements with "AND (NAFLD or NASH)". Studies and medical literature that discussed the roles and usage of herbs and supplements in NAFLD and nonalcoholic steatohepatitis (NASH) from inception until 20 June 2018 were reviewed. Many studies have claimed that the use of various herbs and supplements may improve disease endpoints and outcomes related to NAFLD and/or NASH. Improvement in liver function tests were noted. Amelioration or reduction of lobular inflammation, hepatic steatosis, and fibrosis were also noted. However, well-designed studies demonstrating improved clinical outcomes are lacking. Furthermore, experts remain concerned about the lack of regulation of herbs/supplements and the need for further research on potential adverse effects and herb⁻drug interactions. In conclusion, preliminary data on several herbs have demonstrated promising antioxidant, anti-inflammatory, anti-apoptotic, and anti-adipogenic properties that may help curtail the progression of NAFLD/NASH. Clinical trials testing the safety and efficacy must be completed before widespread can be recommended.

View details for PubMedID 30201879
Emerging Therapeutic Targets and Experimental Drugs for the Treatment of NAFLD. Diseases (Basel, Switzerland) Dibba, P., Li, A. A., Perumpail, B. J., John, N., Sallam, S., Shah, N. D., Kwong, W., Cholankeril, G., Kim, D., Ahmed, A. 2018; 6 (3)
Abstract

The two main subsets of nonalcoholic fatty liver disease (NAFLD) include: (1) nonalcoholic fatty liver (NAFL), the more common and non-progressive subtype; and (2) nonalcoholic steatohepatitis (NASH), the less common subtype, which has the potential to progress to advanced liver damage. Current treatment strategies have focused on lifestyle management of modifiable risk factors, namely weight, and on the optimization of the management of individual components of metabolic syndrome. Various hypothetical pathogenic mechanisms have been proposed, leading to the development of novel drugs with the potential to effectively treat patients with NASH. Numerous clinical trials are ongoing, utilizing these experimental drugs and molecules targeting specific mechanistic pathway(s) to effectively treat NASH. Some of these mechanistic pathways targeted by experimental pharmacologic agents include chemokine receptor 2 and 5 antagonism, inhibition of galectin-3 protein, antagonism of toll-like receptor 4, variation of fibroblast growth factor 19, agonism of selective thyroid hormone receptor-beta, inhibition of apoptosis signal-regulating kinase 1, inhibition of acetyl-coenzyme A carboxylase, agonism of farnesoid X receptor, antibodies against lysl oxidase-like-2, and inhibition of inflammasomes. Emerging data are promising and further updates from ongoing clinical trials are eagerly awaited.

View details for PubMedID 30235807
Judicious Use of Lipid Lowering Agents in the Management of NAFLD. Diseases (Basel, Switzerland) Iqbal, U., Perumpail, B. J., John, N., Sallam, S., Shah, N. D., Kwong, W., Cholankeril, G., Kim, D., Ahmed, A. 2018; 6 (4)
Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world. NAFLD encompasses a spectrum of histological features, including steatosis, steatohepatitis with balloon degeneration, and hepatic fibrosis leading to cirrhosis. In patients with advanced liver damage, NAFLD is associated with an increased risk of hepatocellular carcinoma. Diabetes mellitus, hypertension, and dyslipidemia are components of metabolic syndrome and are commonly associated with NAFLD. Cardiovascular disease is the leading cause of mortality in patients with NAFLD. Therefore, it is important to pre-emptively identify and proactively treat conditions like hyperlipidemia in an effort to favorably modify the risk factors associated with cardiovascular events in patients with NAFLD. The management of hyperlipidemia has been shown to reduce cardiovascular mortality and improve histological damage/biochemical abnormalities associated with non-alcoholic steatohepatitis (NASH), a subset of NAFLD with advance liver damage. There are no formal guidelines available regarding the use of anti-hyperlipidemic drugs, as prospective data are lacking. The focus of this article is to discuss the utility of lipid-lowering drugs in patients with NAFLD.

View details for PubMedID 30249980
Clinical utility of ledipasvir/sofosbuvir in the treatment of adolescents and children with hepatitis C Adolescent Health, Medicine and Therapeutics Yang, C. H., Goel, A., Ahmed, A. 2018; 9: 103—110
Abstract

Chronic infection with hepatitis C virus (HCV) affects an estimated 0.1%-2% of the pediatric population in the United States. While the clinical course in young children is indolent, adolescents who contract HCV have a disease course similar to adults, with a 26-fold increased risk of chronic liver disease-associated mortality, hepatocellular carcinoma, and need for curative liver transplantation. Furthermore, adolescent patients are entering childbearing age and carry a risk of passing HCV to their offspring via vertical transmission. Pegylated-interferon (PEG-IFN) with ribavirin was previously the only treatment option for pediatric patients with chronic hepatitis C (CHC), but the high likelihood of adverse reactions and subcutaneous route of administration limited its use and efficacy. Recently, the direct-acting antivirals (DAAs) ledipasvir (LDV) and sofosbuvir (SOF) were approved for adolescents with CHC. This review discusses the natural history of CHC in pediatric patients, data supporting LDV/SOF in adolescents, and ongoing studies evaluating DAAs in pediatric patients.

View details for DOI 10.2147/AHMT.S147896

View details for PubMedCentralID PMC6071628
Societal Perspectives Analysis for Evaluating Direct-Acting Antiviral Affordability While Awaiting Liver Transplant REPLY HEPATOLOGY Ahmed, A., Beckerman, R., Younossi, Z. M. 2018; 67 (1): 450–51
View details for PubMedID 28960407
Alcoholic Liver Disease Replaces Hepatitis C Virus Infection asthe Leading Indication for Liver Transplantation in the UnitedStates. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Cholankeril, G., Ahmed, A. 2017
View details for PubMedID 29199144
Direct-Acting Antiviral Therapy and Improvement in Graft Survival of Hepatitis C Liver Transplant Recipients TRANSPLANTATION Cholankeril, G., Li, A. A., Yoo, E. R., Ahmed, A. 2017; 101 (12): e349
View details for PubMedID 28846556
Drug-drug interactions in hepatitis C virus treatment: Do they really matter? Clinical liver disease Ahmed, A., Lutchman, G. A., Kwo, P. Y. 2017; 10 (5): 111–15
View details for PubMedID 30992768
Inverse association of marijuana use with nonalcoholic fatty liver disease among adults in the United States PLOS ONE Kim, D., Kim, W., Kwak, M., Chung, G., Yim, J., Ahmed, A. 2017; 12 (10): e0186702
Abstract

The impact of marijuana on nonalcoholic fatty liver disease (NAFLD) is largely unknown. We studied the association between marijuana and NAFLD utilizing cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) from 2005-2014 and NHANES III (1988-1994).Suspected NAFLD was diagnosed if serum alanine aminotransferase (ALT) was > 30 IU/L for men and > 19 IU/L for women in the absence of other liver diseases (NHANES 2005-2014). In NHANES III cohort, NAFLD was defined based on ultrasonography.Of the 14,080 (NHANES 2005-2014) and 8,286 (NHANES III) participants, prevalence of suspected NAFLD and ultrasonographically-diagnosed NAFLD were inversely associated with marijuana use (p < 0.001). Compared to marijuana-naïve participants, marijuana users were less likely to have suspected NAFLD (odds ratio [OR]: 0.90, 95% confidence interval [CI]: 0.82-0.99 for past user; OR: 0.68, 95% CI: 0.58-0.80 for current user) and ultrasonographically-diagnosed NAFLD (OR: 0.75, 95% CI: 0.57-0.98 for current user) in the age, gender, ethnicity-adjusted model. On multivariate analysis, the ORs for suspected NAFLD comparing current light or heavy users to non-users were 0.76 (95% CI 0.58-0.98) and 0.70 (95% CI 0.56-0.89), respectively (P for trend = 0.001) with similar trends in ultrasonographically-diagnosed NAFLD (OR: 0.77, 95% CI: 0.59-1.00 for current user; OR: 0.71, 95% CI: 0.51-0.97 for current light user). In insulin resistance-adjusted model, marijuana use remained an independent predictor of lower risk of suspected NAFLD.In this nationally representative sample, active marijuana use provided a protective effect against NAFLD independent of known metabolic risk factors. The pathophysiology is unclear and warrants further investigation.

View details for PubMedID 29049354
Nutritional Needs and Support for Children with Chronic Liver Disease. Nutrients Yang, C. H., Perumpail, B. J., Yoo, E. R., Ahmed, A., Kerner, J. A. 2017; 9 (10)
Abstract

Malnutrition has become a dangerously common problem in children with chronic liver disease, negatively impacting neurocognitive development and growth. Furthermore, many children with chronic liver disease will eventually require liver transplantation. Thus, this association between malnourishment and chronic liver disease in children becomes increasingly alarming as malnutrition is a predictor of poorer outcomes in liver transplantation and is often associated with increased morbidity and mortality. Malnutrition requires aggressive and appropriate management to correct nutritional deficiencies. A comprehensive review of the literature has found that infants with chronic liver disease (CLD) are particularly susceptible to malnutrition given their low reserves. Children with CLD would benefit from early intervention by a multi-disciplinary team, to try to achieve nutritional rehabilitation as well as to optimize outcomes for liver transplant. This review explains the multifactorial nature of malnutrition in children with chronic liver disease, defines the nutritional needs of these children, and discusses ways to optimize their nutritional.

View details for PubMedID 29035331
Comparing Direct Acting Antivirals-Based Regimens Plus Ribavirin in Treatment-Experienced Hepatitis C Virus Genotype 3 Patients: A Systematic Review and Meta-Analysis Khan, M., Cholankeril, G., Kamal, F., Shrestha, S., March, K. L., Rahim, U., Snyder, H. S., Gadiparthi, C., Hahambis, T. A., Ahmed, A. WILEY. 2017: 846A–847A
View details for Web of Science ID 000412089801724
Can Ribavirin be Avoided in the Management of Hepatitis C Genotype 3 Patients When Treated With Direct Acting Antivirals? A Systematic Review and Meta-Analysis Khan, M., Cholankeril, G., Gadiparthi, C., Siddiqui, M., Haq, K. F., Hahambis, T., Ahmed, A. NATURE PUBLISHING GROUP. 2017: S559–S560
View details for Web of Science ID 000439259002231
Liver Transplantation for Nonalcoholic Steatohepatitis in the US: Temporal Trends and Outcomes DIGESTIVE DISEASES AND SCIENCES Cholankeril, G., Wong, R. J., Hu, M., Perumpail, R. B., Yoo, E. R., Puri, P., Younossi, Z. M., Harrison, S. A., Ahmed, A. 2017; 62 (10): 2915–22
Abstract

Nonalcoholic steatohepatitis (NASH) is a rapidly growing etiology of end-stage liver disease in the US. Temporal trends and outcomes in NASH-related liver transplantation (LT) in the US were studied.A retrospective cohort study utilizing the United Network for Organ Sharing and Organ Procurement and Transplantation (UNOS/OPTN) 2003-2014 database was conducted to evaluate the frequency of NASH-related LT. Etiology-specific post-transplant survival was evaluated with Kaplan-Meier methods and multivariate Cox proportional hazards models.Overall, 63,061 adult patients underwent LT from 2003 to 2014, including 20,782 HCV (32.96%), 9470 ALD (15.02%), and 8262 NASH (13.11%). NASH surpassed ALD and became the second leading indication for LT beginning in 2008, accounting for 17.38% of LT in 2014. From 2003 to 2014, the number of LT secondary to NASH increased by 162%, whereas LT secondary to HCV increased by 33% and ALD increased by 55%. Due to resurgence in ALD, the growth in NASH and ALD was comparable from 2008 to 2014 (NASH +50.15% vs. ALD +41.87%). The post-transplant survival in NASH was significantly higher compared to HCV (5-year survival: NASH -77.81%, 95% CI 76.37-79.25 vs. HCV -72.15%, 95% CI 71.37-72.93, P < .001). In the multivariate Cox proportional hazards model, NASH demonstrated significantly higher post-transplant survival compared to HCV (HR 0.75; 95% CI 0.71-0.79, P < .001).Currently, NASH is the most rapidly growing indication for LT in the US. Despite resurgence in ALD, NASH remains the second leading indication for LT.

View details for PubMedID 28744836
Post-Transplant Complications in Obese Liver Transplant Recipients: A Systematic Review and Meta-Analysis Kamal, F., Khan, M., Ahmed, A., Nair, S., Ismail, M. K., Satapathy, S. K. WILEY. 2017: 916A
View details for Web of Science ID 000412089802075
Health Outcomes Associated with Sofosbuvir- based Single-Tablet Regimens for Initial and Re-treatment of Chronic Hepatitis C in the US Gordon, S. C., Ahmed, A., Saab, S., Dieterich, D. T., Wong, R. J., Kugelmas, M., Brown, K. A., Younossi, Z. M. WILEY. 2017: 635A–636A
View details for Web of Science ID 000412089801322
Is Obesity associated with Increased Risk of Mortality and Re-transplantation in Liver Transplant Recipients? A Systematic Review and Meta-Analysis Kamal, F., Khan, M., Ahmed, A., Nair, S., Ismail, M. K., Satapathy, S. K. WILEY. 2017: 919A
View details for Web of Science ID 000412089802081
Liver Transplant (LT) Candidates with Primary Biliary Cholangitis (PBC) Experience Higher Wait List Mortality: Data from the Scientific Registry of Transplant Recipients (SRTR) Younossi, Z. M., Stepanova, M., de Avila, L., Ahmed, A., Wong, R. J., Saab, S., Kowdley, K. V., Brown, K. A., Kugelmas, M., Racila, A. WILEY. 2017: 176A–177A
View details for Web of Science ID 000412089800313
Demographics and Clinical Characteristics of Hepatitis C Virus-Positive Donors and Recipients Li, A. A., Yoo, E. R., Sandhu, K., Perumpail, R. B., Cholankeril, G., Kim, D., Ahmed, A. WILEY. 2017: 894A–895A
View details for Web of Science ID 000412089802034
Declining Rate of Acute Graft Failure in Liver Transplant Recipients with Hepatitis C Cholankeril, G., Li, A. A., Yoo, E. R., Gonzalez, S. A., Nair, S., Ahmed, A. WILEY. 2017: 527A–528A
View details for Web of Science ID 000412089801128
Rising Trend and Poor Waitlist Outcomes in Young Adult Liver Transplant Registrants with Alcoholic Liver Disease Cholankeril, G., Gadiparthi, C., Rahim, U., Goel, A., Puri, P., Sarin, S. K., Ahmed, A. WILEY. 2017: 943A–944A
View details for Web of Science ID 000412089802129
Hispanics with Primary Biliary Cholangitis present for Liver Transplant Listing at a Younger Age and with more Severe Hepatic Decompensation Yoo, E. R., Li, A. A., Imam, M., Hu, M., Cholankeril, G., Lindor, K. D., Ahmed, A. WILEY. 2017: 174A–175A
View details for Web of Science ID 000412089800309
Poor Post-Transplant Survival in Donation after Cardiac Death (DCD)-related Liver Transplant Recipients with Severe Hepatic Decompensation Cholankeril, G., Rahim, U., Gadiparthi, C., Gonzalez, S. A., Ahmed, A. WILEY. 2017: 881A
View details for Web of Science ID 000412089802009
Optimizing the Nutritional Support of Adult Patients in the Setting of Cirrhosis NUTRIENTS Perumpail, B. J., Li, A. A., Cholankeril, G., Kumari, R., Ahmed, A. 2017; 9 (10)
View details for DOI 10.3390/nu9101114

View details for Web of Science ID 000414629900070
Increasing Acceptance of Severe Acute Alcoholic Hepatitis as an Indication for Liver Transplantation with Outcomes comparable to Fulminant Hepatic Failure Cholankeril, G., Liu, A., Sandhu, J., Yoo, E. R., Li, A. A., Goel, A., Puri, P., Sarin, S. K., Ahmed, A. WILEY. 2017: 18A
View details for Web of Science ID 000412089800033
Nonalcoholic Steatohepatitis Remains the Fastest Growing Indication for Liver Transplantation in Patients with Hepatocellular Carcinoma in the United States Li, A. A., Yoo, E. R., Cholankeril, G., Kim, D., Puri, P., Harrison, S. A., Younossi, Z. M., Ahmed, A. WILEY. 2017: 749A
View details for Web of Science ID 000412089801539
Trends in Liver Transplantation among Patients with Primary Biliary Cholangitis Cholankeril, R., Rahim, U., Yoo, E. R., Li, A. A., Sandhu, K., Perumpail, R. B., Hu, M., Cholankeril, G., Ahmed, A. WILEY. 2017: 198A–199A
View details for Web of Science ID 000412089800354
National Drug Overdose Epidemic is a Significant Contributor to Deceased Donor Liver Organ Pool Cholankeril, G., Li, A. A., Cholankeril, R., Sandhu, J., Kim, D., Ahmed, A. WILEY. 2017: 397A
View details for Web of Science ID 000412089800738
Need to Improve Organs Transplanted Per Donor Despite the Rising Utilization of Hepatitis C Virus-Positive Donors in the United States Li, A. A., Rahim, U., Yoo, E. R., Cholankeril, G., Kim, D., Ahmed, A. WILEY. 2017: 887A
View details for Web of Science ID 000412089802020
Implementation of Share 35 Policy has Improved Survival following Liver Transplantation Cholankeril, G., Li, A. A., Nair, S., Ahmed, A., Stanford Univ WILEY. 2017: 883A
View details for Web of Science ID 000412089802012
Rifaximin for the prevention of spontaneous bacterial peritonitis and hepatorenal syndrome in cirrhosis: a systematic review and meta-analysis EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY Kamal, F., Khan, M., Khan, Z., Cholankeril, G., Hammad, T. A., Lee, W. M., Ahmed, A., Waters, B., Howden, C. W., Nair, S., Satapathy, S. K. 2017; 29 (10): 1109–17
Abstract

Prophylactic antibiotics have been recommended in patients with a previous history of spontaneous bacterial peritonitis (SBP). Recently, there has been interest in the use of rifaximin for the prevention of SBP and hepatorenal syndrome (HRS). We conducted a meta-analysis to evaluate this association of rifaximin. We searched several databases from inception through 24 January 2017, to identify comparative studies evaluating the effect of rifaximin on the occurrence of SBP and HRS. We performed predetermined subgroup analyses based on the type of control group, design of the study, and type of prophylaxis. Pooled odds ratios (ORs) were calculated using a random effects model. We included 13 studies with 1703 patients in the meta-analysis of SBP prevention. Pooled OR [95% confidence interval (CI)] was 0.40 (95% CI: 0.22-0.73) (I=58%). On sensitivity analysis, adjusted OR was 0.29 (95% CI: 0.20-0.44) (I=0%). The results of the subgroup analysis based on type of control was as follows: in the quinolone group, pooled OR was 0.42 (95% CI: 0.14-1.25) (I=55%), and in the no antibiotic group, pooled OR was 0.40 (95% CI: 0.18-0.86) (I=64%). However, with sensitivity analysis, benefit of rifaximin was demonstrable; pooled ORs were 0.32 (95% CI: 0.17-0.63) (I=0%) and 0.28 (95% CI: 0.17-0.45) (I=0%) for the comparison with quinolones and no antibiotics, respectively. Pooled OR based on randomized controlled trials was 0.41 (95% CI: 0.22-0.75) (I=13%). For the prevention of HRS, the pooled OR was 0.25 (95% CI: 0.13-0.50) (I=0%). Rifaximin has a protective effect against the development of SBP in cirrhosis. However, the quality of the evidence as per the GRADE framework was very low. Rifaximin appeared effective for the prevention of HRS.

View details for PubMedID 28763340
Improved Short-Term Survival in HCV Patients following Liver Transplantation in the Era of Direct Acting Antiviral Agents Cholankeril, G., Li, A. A., Yoo, E. R., Gonzalez, S. A., Younossi, Z. M., Ahmed, A. WILEY. 2017: 2A–3A
View details for Web of Science ID 000412089800005
Alcohol Liver Disease is now the most rapidly rising Indication for Liver Transplant Waitlist Registration in the United States Rahim, U., Cholankeril, G., Yoo, E. R., Liu, A., Li, A. A., Kim, D., Kwo, P. Y., Ahmed, A., Goel, A. WILEY. 2017: 708A
View details for Web of Science ID 000412089801457
The Declining Burden of HCV on the Liver Transplant Waitlist associated with the DAA era Cholankeril, G., March, K. L., Yoo, E. R., Li, A. A., Cholankeril, R., Perumpail, R. B., Satapathy, S. K., Ahmed, A. WILEY. 2017: 72A
View details for Web of Science ID 000412089800124
Hepatocellular Carcinoma results in Highest Number of Malignancy-related Hospitalizations in Baby Boomers Gadiparthi, C., Yoo, E. R., Liu, A., Hu, M., Kim, D., Cholankeril, G., Howden, C. W., Ahmed, A. WILEY. 2017: 774A
View details for Web of Science ID 000412089801587
Hepatocellular Carcinoma in Baby Boomers is associated with High Rates of Inpatient Morbidty and Mortality Yoo, E. R., Gadiparthi, C., Hu, M., Cholankeril, G., Ahmed, A. WILEY. 2017: 773A–774A
View details for Web of Science ID 000412089801586
Severe Hepatic Encephalopathy is an Independent Predictor of Waitlist Mortality in Patients with High MELD Gadiparthi, C., Yoo, E. R., Hu, M., Cholankeril, G., Howden, C. W., Ahmed, A. WILEY. 2017: 908A
View details for Web of Science ID 000412089802059
Rising Rates of Hepatocellular Carcinoma Leading to Liver Transplantation in Baby Boomer Generation with Chronic Hepatitis C, Alcohol Liver Disease, and Nonalcoholic Steatohepatitis-Related Liver Disease. Diseases (Basel, Switzerland) Cholankeril, G., Yoo, E. R., Perumpail, R. B., Liu, A., Sandhu, J. S., Nair, S., Hu, M., Ahmed, A. 2017; 5 (4)
Abstract

We aim to study the impact of the baby boomer (BB) generation, a birth-specific cohort (born 1945-1965) on hepatocellular carcinoma (HCC)-related liver transplantation (LT) in patients with chronic hepatitis C virus (HCV), alcoholic liver disease (ALD), and non-alcoholic steatohepatitis (NASH). We performed a retrospective analysis using the United Network for Organ Sharing (UNOS)/Organ Procurement Transplant Network (OPTN) database from 2003 to 2014 to compare HCC-related liver transplant surgery trends between two cohorts-the BB and non-BB-with a secondary diagnosis of HCV, ALD, or NASH. From 2003-2014, there were a total of 8313 liver transplant recipients for the indication of HCC secondary to HCV, ALD, or NASH. Of the total, 6658 (80.1%) HCC-related liver transplant recipients were BB. The number of liver transplant surgeries for the indication of HCC increased significantly in NASH (+1327%), HCV (+382%), and ALD (+286%) during the study period. The proportion of BB who underwent LT for HCC was the highest in HCV (84.7%), followed by NASH (70.3%) and ALD (64.7%). The recommendations for birth-cohort specific HCV screening stemmed from a greater understanding of the high prevalence of chronic HCV and HCV-related HCC within BB. The rising number of HCC-related LT among BB with ALD and NASH suggests the need for increased awareness and improved preventative screening/surveillance measures within NASH and ALD cohorts as well.

View details for PubMedID 28954412
Beneficial Effects of Statins on the Rates of Hepatic Fibrosis, Hepatic Decompensation, and Mortality in Chronic Liver Disease: A Systematic Review and Meta-Analysis. American journal of gastroenterology Kamal, S., Khan, M. A., Seth, A., Cholankeril, G., Gupta, D., Singh, U., Kamal, F., Howden, C. W., Stave, C., Nair, S., Satapathy, S. K., Ahmed, A. 2017
Abstract

Statins may improve outcomes in patients with chronic liver disease (CLD). We conducted a systematic review and meta-analysis to evaluate the impact of statins in the setting of CLD.We searched several databases from inception to 17 October 2016 to identify comparative studies evaluating the role of statins in CLD. Outcomes of interest were the associations between statin use and progression of fibrosis, development of hepatic decompensation in cirrhosis, and mortality in CLD. Adjusted hazard ratios (HRs) were pooled and analyzed using a random effects model. Subgroup analyses were performed based on the method of detection for progression of hepatic fibrosis and quality of studies.We included 10 studies (1 randomized controlled trial and 9 observational) with 259,453 patients (54,441 statin users and 205,012 nonusers). For progression of hepatic fibrosis, pooled HR (95% confidence interval) was 0.49 (0.39-0.62). On subgroup analysis of studies using ICD-9 (The International Classification of Diseases, Ninth Revision) coding and a second method to detect cirrhosis, pooled HR was 0.58 (0.51-0.65); pooled HR for studies using ICD-9 coding only was 0.36 (0.29-0.44). For progression of fibrosis in patients with hepatitis C virus (HCV) infection, pooled HR was 0.52 (0.37-0.73). For hepatic decompensation in cirrhosis, pooled HR was 0.54 (0.46-0.65). For mortality, pooled HR based on observational studies was 0.67 (0.46-0.98); in the randomized controlled trial, HR was 0.39 (0.15-0.99). However, the quality of evidence for these associations is low as most included studies were retrospective in nature and limited by residual confounding.Statins may retard the progression of hepatic fibrosis, may prevent hepatic decompensation in cirrhosis, and may reduce all-cause mortality in patients with CLD. As the quality (certainty) of evidence is low, further studies are needed before statins can be routinely recommended.Am J Gastroenterol advance online publication, 6 June 2017; doi:10.1038/ajg.2017.170.

View details for DOI 10.1038/ajg.2017.170

View details for PubMedID 28585556
Optimal Timing for Hepatitis C Antiviral Therapy in the Peri-Transplant Period? Hepatology (Baltimore, Md.) Cholankeril, G., Wong, R. J., Kim, D., Ahmed, A. 2017
View details for DOI 10.1002/hep.29300

View details for PubMedID 28586088
Cirrhosis Patients with Nonalcoholic Steatohepatitis Are Significantly Less Likely to Receive Surveillance for Hepatocellular Carcinoma. Digestive diseases and sciences Tavakoli, H., Robinson, A., Liu, B., Bhuket, T., Younossi, Z., Saab, S., Ahmed, A., Wong, R. J. 2017
Abstract

Disparities in receipt of hepatocellular carcinoma (HCC) surveillance contribute to disparities in overall survival outcomes.We aim to evaluate disparities in receipt of routine HCC surveillance among patients with cirrhosis in a large urban safety-net hospital.Consecutive adults (age ≥ 18) with cirrhosis from July 1, 2014, to December 31, 2015, were retrospectively evaluated to determine rates of receiving appropriate HCC surveillance within 6 months and 1 year after diagnosis of cirrhosis. Rates of HCC surveillance were stratified by sex, race/ethnicity, and liver disease etiology. Multivariate Cox proportional hazards models were utilized to evaluate for predictors of receiving appropriate HCC surveillance.Among 157 cirrhosis patients enrolled [hepatitis C virus (HCV): 29.9%, hepatitis B virus: 13.4%, alcoholic cirrhosis: 44.6%, nonalcoholic steatohepatitis (NASH): 8.9%], mean age of cirrhosis diagnosis was 53.8 ± 9.0 years. Among these patients, 49% received (n = 77) HCC surveillance within 6 months and 78% (n = 123) were surveyed within 1 year of cirrhosis diagnosis. On multivariate analyses, patients with NASH cirrhosis were significantly less likely to receive HCC surveillance compared with chronic HCV cirrhosis patients (HR 0.44, 95% CI 0.19-0.99, p < 0.05). No significant sex-specific or race/ethnicity-specific disparities in receipt of HCC surveillance were observed.Among a diverse safety-net hospital population, sub-optimal HCC surveillance rates were observed: Only 49% of cirrhosis patients received HCC surveillance within 6 months, and 78% of cirrhosis patients received HCC surveillance within 1 year. Differences in rates of HCC screening by liver disease etiology were observed.

View details for DOI 10.1007/s10620-017-4595-x

View details for PubMedID 28474143
The value of cure associated with treating treatment-naive chronic hepatitis C genotype 1: Are the new all-oral regimens good value to society? LIVER INTERNATIONAL Younossi, Z. M., Park, H., Dieterich, D., Saab, S., Ahmed, A., Gordon, S. C. 2017; 37 (5): 662-668
View details for DOI 10.1111/liv.13298

View details for Web of Science ID 000400384300006
The Role of e-Health in Optimizing Task-Shifting in the Delivery of Antiviral Therapy for Chronic Hepatitis C. Telemedicine journal and e-health Yoo, E. R., Perumpail, R. B., Cholankeril, G., Jayasekera, C. R., Ahmed, A. 2017
Abstract

Recently, we reported the successful application of task-shifting to improve the management of patients with chronic hepatitis C virus (HCV) infection receiving treatment with direct-acting antiviral (DAA) agents in underserved areas of California. We assessed the impact of e-health on task-shifting in our treatment model.In a retrospective analysis, we reviewed the impact of e-health on optimizing the delivery of DAA-based regimen to HCV-infected patients in outreach clinics in medically underserved areas of California. A nonphysician healthcare provider worked in close conjunction with a hepatologist to monitor the patients during the course of antiviral therapy. We exclusively used our institution-based, secured e-health portal as the means of communication with the local staff and patients in outreach clinics.From January 2015 to June 2016, we treated over 100 HCV-infected patients with DAA-based regimens using the task-shifting model. During the study period, we did not experience any delay in the care of our patients undergoing treatment with DAA agents. Communication with the patient and staff using e-health was prompt, secured, and documented in electronic medical records. Due to the optimization of task-shifting by e-health and safety/tolerability of DAA, 95% patients did not need a follow-up clinic visit during the treatment. Return clinic visits during the treatment were unrelated to DAA use or associated with ribavirin-related anemia. In addition, we noted improvement in access and capacity of our outreach clinic.We report a positive impact of e-health in optimizing task-shifting for DAA in HCV-infected patients in underserved outreach clinics. More importantly, a secondary improvement in access and capacity of our clinic was noted.

View details for DOI 10.1089/tmj.2016.0189

View details for PubMedID 28375820
Patients With Diabetes and Chronic Liver Disease Are at Increased Risk for Overall Mortality: A Population Study From the United States. Clinical diabetes : a publication of the American Diabetes Association Stepanova, M., Clement, S., Wong, R., Saab, S., Ahmed, A., Younossi, Z. M. 2017; 35 (2): 79-83
Abstract

IN BRIEF Chronic liver disease (CLD) and type 2 diabetes have both been linked to increased morbidity and mortality. In this study, the impact of CLD and diabetes on all-cause mortality was quantified at the population level using U.S. population data. Both type 2 diabetes and CLD were found to be independently associated with increased mortality (age-adjusted hazard ratio [aHR] 1.98 and 1.37 for diabetes and CLD, respectively), and having both diabetes and CLD substantially increased the risk of mortality (aHR 2.41).

View details for DOI 10.2337/cd16-0018

View details for PubMedID 28442821
The Role of Direct-acting Antivirals in the Treatment of Children with Chronic Hepatitis C. Journal of clinical and translational hepatology Yang, C. H., Yoo, E. R., Ahmed, A. 2017; 5 (1): 59-66
Abstract

In the United States, chronic infection with the hepatitis C virus (HCV) affects an estimated 0.1-2% of the pediatric population, who are consequently at risk for major complications, including cirrhosis, hepatocellular carcinoma, and death. The current standard of treatment for chronic hepatitis C (CHC) in children is pegylated-interferon-alpha (PEG-IFN) in combination with ribavirin. PEG-IFN/ribavirin therapy is approved for children ages 3 and older; however, it is often held from use until adulthood because of its extensive list of potential side effects and high likelihood of causing adverse symptoms. While CHC is usually indolent in children and adolescents, immediately treating and curbing the spread of HCV before adulthood is important, as there can be transmission to other individuals via sexual activity and infected females can later vertically transmit the infection during pregnancy, the latter representing the most common means of transmission for children in the United States. The recent development of direct-acting antivirals has shown promising results in clinical trials for use in children and has dramatically increased the rates of sustained virological response in adults while improving side effect profiles as compared to interferon-based treatments. Given the usually indolent course of CHC in children, significant side effects of the currently-approved PEG-IFN/ribavirin therapy, and likely availability of all-oral interferon-free regimens for children within a few years, deferring treatment in clinically-stable children with CHC in anticipation of upcoming superior treatment modalities may be justified.

View details for DOI 10.14218/JCTH.2016.00053

View details for PubMedID 28507928
Sofosbuvir Use in the Setting of End-stage Renal Disease: A Single Center Experience. Journal of clinical and translational hepatology Aggarwal, A., Yoo, E. R., Perumpail, R. B., Cholankeril, G., Kumari, R., Daugherty, T. J., Lapasaran, A. S., Ahmed, A. 2017; 5 (1): 23-26
Abstract

Background and Aims: Patients with chronic hepatitis C (CHC) and end-stage renal disease (ESRD) who are dialysis-dependent form a unique group, in which safety, tolerability and efficacy of sofosbuvir (SOF)-based direct-acting antivirals (DAAs) need further evaluation. Methods: We performed a retrospective analysis of 14 patients with CHC and ESRD on dialysis who received 15 courses of SOF-based therapy. We evaluated dose escalation to standard-dose SOF in this proof-of-principle experience. Results: Sustained virological response (defined as undetectable viral load at 12 weeks, SVR-12) was achieved in 13 out of the 15 (86.7%) treatment courses. Seven (46.6%) patients received reduced half dose as conservative proof-of-principal to mitigate potential toxicity. In 13 out of 15 treatment courses, patients completed the designated treatment duration. One patient was treated twice and developed SVR-12 with the retreatment. One patient was lost to follow-up and counted as a non-responder. Premature discontinuations were not due to DAA-related adverse effects. There were no reports of severe adverse effects or drug interactions. Conclusion: We treated CHC patients with ESRD using dose escalation to standard-dose SOF in this proof-of-principle experience and achieved SVR rates comparable to general population.

View details for DOI 10.14218/JCTH.2016.00060

View details for PubMedID 28507922
Sofosbuvir-based Regimens with Task Shifting Is Cost-effective in Expanding Hepatitis C Treatment Access in the United States. Journal of clinical and translational hepatology Jayasekera, C. R., Beckerman, R., Smith, N., Perumpail, R. B., Wong, R. J., Younossi, Z. M., Ahmed, A. 2017; 5 (1): 16-22
Abstract

Background and Aims: The current paradigm of specialist physician-managed treatment of chronic hepatitis C virus infection (HCV) is inefficient in absorbing the approximately 3 million patients awaiting treatment in the United States. Task shifting-whereby specialist physicians screen patients for treatment eligibility but on-treatment monitoring is devolved to more abundant non-physician clinicians-achieves non-inferior treatment outcomes with second generation direct-acting antivirals (2(nd) Gen DAAs), may increase treatment capacity, and may facilitate greater treatment access. We determined the cost effectiveness of 2(nd) Gen DAAs with respect to interferon-based first-generation DAAs (1(st) Gen DAAs) within a task-shifted treatment model. Methods: Using a previously described decision-analytic Markov structure, we modeled a hypothetical cohort of 1,000 patients with HCV genotype 1 infection over a lifetime horizon, based upon our outreach clinic's HCV treatment protocol. Treatment-naïve and treatment-experienced HCV cohorts were modeled separately, based upon our outr8each clinic's demographics. Treatment response to 2(nd) Gen DAAs was modeled based on our outreach clinic's data. Adverse events, utility, costing, and transition probabilities were sourced from the literature. Results: Driven by improved effectiveness and safety, as well as an expected increase in treatment capacity, 2(nd) Gen DAAs treatment monitored by non-physician clinicians was projected to improve health outcomes and be dominant from a cost-effective perspective versus that of 1(st) Gen DAAs. Trends were consistent across all assessed patient subpopulations. Conclusions: Based on an assumption of increased treatment capacity accompanying a task-shifted treatment model, 2(nd) Gen DAAs-based treatment was cost effective and cost saving as compared to 1(st) Gen DAAs-based treatment for all HCV patient subgroups assessed.

View details for DOI 10.14218/JCTH.2016.00052

View details for PubMedID 28507921
Long-term trends in chronic hepatitis B virus infection associated liver transplantation outcomes in the United States. Journal of viral hepatitis Young, K., Liu, B., Bhuket, T., Younossi, Z., Saab, S., Ahmed, A., Wong, R. J. 2017
Abstract

With effective antiviral therapies, rates of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and decompensated liver disease requiring liver transplantation (LT) are expected to decrease. We aim to evaluate overall trends in LT waitlist registrations, waitlist survival and likelihood of receiving LT among chronic HBV patients in the United States. Using the United Network for Organ Sharing database, we retrospectively evaluated adults (age≥18) with chronic HBV (with and without HCC) listed for LT from 1992 to 1996 (Era 1) vs 1997 to 2004 (Era 2) vs 2005-2015 (Era 3). Multivariate Cox-regression models evaluated probability of waitlist survival and receiving LT. Overall, 6797 chronic HBV adults were listed for LT. While the total number of HBV patients listed for LT remained stable, the proportion of HBV patients with HCC increased from 5.4% in Era 1 to 39.0% in Era 3. Compared to Era 1, waitlist mortality was higher in Era 2 (HR: 4.55, P<.001) and Era 3 (HR: 3.63, P<.001). However, in the most recent era, waitlist mortality significantly improved (compared to 2005-2007: 2008-2011: HR: 0.74, P=.05, 95% CI: 0.55-0.99; 2012-2015: HR: 0.53, P<.001, 95% CI: 0.38-0.75). Probability of receiving LT was also lower with latter time periods (compared to 2005-2007: 2008-2011: HR: 0.77, P<.001 95% CI: 0.68-0.86; 2012-2015: HR: 0.61, P<.001, 95% CI: 0.54-0.69). Although the number of HBV patients requiring LT remained stable, the proportion of HBV patients with HCC continues to rise. The decrease in waitlist mortality and lower likelihood of LT among HBV patients may reflect the effectiveness of antiviral therapies in delaying disease progression in the current era.

View details for DOI 10.1111/jvh.12703

View details for PubMedID 28273387
Treatment of Patients Waitlisted for Liver Transplant with an All-Oral DAAs is a Cost-Effective Treatment Strategy in the United States. Hepatology Ahmed, A., Gonzalez, S. A., Cholankeril, G., Perumpail, R. B., McGinnis, J., Saab, S., Beckerman, R., Younossi, Z. M. 2017
Abstract

All-oral direct acting antivirals (DAAs) have been shown to have high safety and efficacy in treating patients with Hepatitis C (HCV) awaiting liver transplant (LT). However, there is limited empirical evidence comparing the health and economic outcomes associated with treating patients pre- vs. post-LT. The objective of this study was to analyze the cost-effectiveness of pre- vs. post-LT treatment with an all-oral DAA regimen among HCV patients with HCC (hepatocellular carcinoma) or DCC (decompensated cirrhosis).We constructed decision-analytic Markov models of the natural disease progression of HCV in HCC patients and DCC patients waitlisted (WL) for LT. The model followed hypothetical cohorts of 1,000 patients with a mean age 50 over a 30 year time horizon from a third-party US payer perspective, and estimated their health and cost outcomes based on pre- vs. post-LT treatment with an all-oral DAA regimen. Transition probabilities and utilities were based on the literature and hepatologist consensus. Sustained viral response (SVR) rates were sourced from ASTRAL-4 and SOLAR-1, -2. Costs were sourced from RedBook, Medicare fee schedules, and published literature.In the HCC analysis, the pre-LT treatment strategy resulted in 11.48 per-patient quality-adjusted life years (QALYs) and $365,948 per patient lifetime costs vs. 10.39 and $283,696 in the post-LT arm. In the DCC analysis, the pre-LT treatment strategy results in 9.27 per-patient QALYs and $304,800 per patient lifetime costs vs. 8.7 and $283,789 in the post-LT arm. As such, the pre-LT treatment strategy was found to be the most cost-effective in both populations with an incremental cost-effectiveness ratio of $74,255 (HCC) and $36,583 (DCC). Sensitivity and scenario analyses showed results were most sensitive to the utility of patients post-LT, treatment SVR rates, LT costs, and baseline MELD score (DCC analysis only).The timing of initiation of antiviral treatment for HCV patients with HCC or DCC relative to LT is an important area of clinical and policy research. Our results indicate that pre-LT treatment with a highly effective, all-oral DAA regimen provides the best health outcomes and is the most cost-effective strategy for the treatment of HCV patients with HCC or DCC waitlisted for LT. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/hep.29137

View details for PubMedID 28257591
Treating Medicaid patients with hepatitis C: clinical and economic impact. American journal of managed care Younossi, Z., Gordon, S. C., Ahmed, A., Dieterich, D., Saab, S., Beckerman, R. 2017; 23 (2): 107-112
Abstract

To estimate change in chronic hepatitis C virus (HCV) disease and the economic burden associated with comprehensive treatment of the chronic HCV-infected Medicaid population.Decision-analytic Markov model.Treatment-naïve patients with genotype 1 chronic HCV were followed over a lifetime horizon from the third-party payer perspective. Patients entered the model insured under Medicaid and were treated under state-specific restrictions by Metavir fibrosis stage (base case) or all treated (all-patient strategy) with an approved all-oral regimen (ledipasvir/sofosbuvir [LDV/SOF] for 8 weeks or 12 weeks, depending on cirrhosis status, viral load, and state-specific LDV/SOF restrictions). Untreated patients were assumed to age into Medicare at 65 years, where they were treated with LDV/SOF without restriction by fibrotic stage.The sustained virologic response (SVR) rate of the current Medicaid LDV/SOF restriction strategy was 75.2% versus 95.9% if all LDV/SOF-eligible patients were treated under Medicaid. Treating all eligible Medicaid patients with LDV/SOF, regardless of fibrotic stage, was projected to result in 36,752 fewer cases of cirrhosis; 1739 fewer liver transplants; 8169 fewer cases of hepatocellular carcinoma; 16,173 fewer HCV-related deaths; 0.84 additional life-years per patient; and 1.03 additional quality-adjusted life-years per patient. Treating all Medicaid patients with chronic HCV using LDV/SOF resulted in a 39.4% ($3.8 billion) savings and decreased the proportion of total costs attributable to downstream costs of care to 18.3%.A "treat all" strategy in a Medicaid population resulted in superior SVRs, substantial reductions in downstream negative clinical outcomes, and considerable cost savings. Current restrictive state policies regarding HCV treatment in Medicaid populations must be reassessed in light of these data.

View details for PubMedID 28245654
Disparities in Liver Transplantation Resulting From Variations in Regional Donor Supply and Multiple Listing Practices CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Cholankeril, G., Yoo, E. R., Perumpail, R. B., Younossi, Z. M., Ahmed, A. 2017; 15 (2): 313-315
View details for DOI 10.1016/j.cgh.2016.08.036

View details for Web of Science ID 000397246400029
Real-world experience with interferon-free, direct acting antiviral therapies in Asian Americans with chronic hepatitis C and advanced liver disease. Medicine Chang, C. Y., Nguyen, P., Le, A., Zhao, C., Ahmed, A., Daugherty, T., Garcia, G., Lutchman, G., Kumari, R., Nguyen, M. H. 2017; 96 (6)
Abstract

Real-life data on interferon (IFN)-free direct acting antiviral (DAA) therapies for chronic hepatitis C (CHC) is limited for Asian Americans.To evaluate sustained virologic response (SVR) and adverse events (AE) in Asian Americans treated with sofosbuvir (SOF)-based, IFN-free DAA therapies.This is a retrospective study of 110 consecutive Asian Americans with HCV genotypes 1 to 3 or 6 treated with IFN-free SOF-based regimens for 8 to 24 weeks between February 2014 and March 2016 at a university center in Northern California.Mean age was 63 ± 12 years, mean BMI was 25 ± 6 (kg/m), and about half (52%) were male. Most patients were infected with HCV genotype 1 (HCV-1, 64%), followed by HCV-2 (14%), HCV-6 (13%), and HCV-3 (8%). Half had cirrhosis, and the majority of these (67%) had decompensation. Overall SVR12 was 93% (102/110), and highest among patients without cirrhosis, liver transplant, or HCC (100%, 37/37). SVR12 was lower among patients with HCC (82%, 14/17), decompensated cirrhosis (84%, 31/37), or liver transplant (89%, 17/19), regardless of treatment and genotype. Most common AEs were anemia (25%), fatigue (20%), and headache (12%). Anemia was highest in patients receiving SOF/RBV (67%). There was 1 treatment-unrelated serious adverse effect (SAE). There were 7 dose reductions due to anemia or fatigue from RBV and 2 treatment discontinuations due to fatigue or loss of insurance authorization.This real-life cohort of Asian American CHC patients treated with IFN-free SOF-based therapies showed high overall treatment response and good tolerability, despite very high rates of advanced disease and prior treatment failure.

View details for DOI 10.1097/MD.0000000000006128

View details for PubMedID 28178174
Improved Outcomes in HCV Patients Following Liver Transplantation During the Era of Direct Acting Antiviral Agents. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Cholankeril, G., Li, A. A., March, K. L., Yoo, E. R., Kim, D., Snyder, H., Gonzalez, S. A., Younossi, Z. M., Ahmed, A. 2017
View details for PubMedID 28838786
Expanding Treatment Access for Chronic Hepatitis C with Task-shifting in the Era of Direct-acting Antivirals. Journal of clinical and translational hepatology Yoo, E. R., Perumpail, R. B., Cholankeril, G., Jayasekera, C. R., Ahmed, A. 2017; 5 (2): 130–33
Abstract

In the United States, the fight to eradicate hepatitis C virus (HCV) infection has been ongoing for many years, but the results have been less than ideal. Historically, patients with chronic hepatitis C (CHC) were treated with interferon-based regimens, which were associated with frequent adverse effects, suboptimal response rates, and long durations of treatment - of up to 48 weeks. Expertise from specialist-physicians, such as hepatologists and gastroenterologists, was needed to closely follow patients on these medications so as to monitor laboratory values and manage adverse effects. However, the emergence of direct-acting antiviral (DAA) agents against HCV infection have heralded outstanding progress in terms of safety, tolerability, lack of adverse effects, efficacy, and truncated duration of therapy - 12 weeks or less - thereby making the need for close monitoring by specialist-physicians obsolete. With the recent approval of DAA agents by the Food and Drug Administration, the treatment model for CHC no longer relies on the limited number of specialist-physicians, which represented a major barrier to treatment access in the past, especially in underserved areas of the United States. We propose and share our experiences in adapting a task-shifting treatment model, one that utilizes a relatively larger pool of non-specialist healthcare providers, such as nursing staff (medical assistants, vocational licensed nurses, registered nurses, etc.) and advanced practice providers (nurse practitioners and physician assistants), to perform a variety of important clinical functions in an effort to make DAA-based antiviral therapy widely available against HCV infection. Most recently, task-shifting was implemented by the United States and World Health Organization in the fight against the human immunodeficiency virus and showed encouraging results. Based on our experiences in implementing this model at our outreach clinics, the majority of HCV-infected patients treated with DAA agents can be easily monitored by non-specialist healthcare providers and physician extenders. Task-shifting can effectively address one of the major rate-limiting factors in expanding treatment access for HCV infection.

View details for PubMedID 28660150
Extrahepatic Manifestations of Hepatitis C Virus After Liver Transplantation. Clinics in liver disease Wong, R. J., Saab, S., Ahmed, A. 2017; 21 (3): 595–606
Abstract

Chronic hepatitis C virus (HCV) infection remains a leading cause of chronic liver disease in the United States. Although the hepatic impact of chronic HCV leading to cirrhosis and the need for liver transplantation is paramount, the extrahepatic manifestations of chronic HCV infection are equally important. In particular, a better understanding of the prevalence and impact of extrahepatic manifestations of chronic HCV infection in the post-liver transplant setting relies on understanding the interplay between the effects of chronic HCV infection in a posttransplant environment characterized by strong immunosuppression and the associated risks of this milieu.

View details for PubMedID 28689596
Rising Rate of Liver Transplantation in the Baby Boomer Generation with Non-alcoholic Steatohepatitis in the United States. Journal of clinical and translational hepatology Siddique, O., Joseph-Talreja, M., Yoo, E. R., Perumpail, R. B., Cholankeril, G., Harrison, S. A., Younossi, Z. M., Wong, R. J., Ahmed, A. 2017; 5 (3): 193–96
Abstract

Background and Aims: Nonalcoholic steatohepatitis (NASH) is the most rapidly growing indication for liver transplantation (LT) in the United States and is on a trajectory to become the leading indication for LT in the next decade. We aimed to study the trends in NASH-related LT among persons born between 1945 and 1965, the baby boomer (BB) generation. Methods: We performed a retrospective cohort analysis using population-based data from the United Network for Organ Sharing/Organ Procurement and Transplantation Network registry from 2004-2015 to evaluate the birth cohort-specific trends in liver transplant waitlist registrations and liver transplant surgeries in patients with NASH. We stratified our study population into three birth cohorts: 1) birth before 1945, 2) birth between 1945 and 1965, and 3) birth after 1965. Results: The overall rates of NASH-related waitlist registrations and liver transplant surgeries steadily increased from 2004 to 2015 and were reflective of a sharp rise noted in the NASH BB sub-group. From 2004 to 2015, the proportion of BB patients with NASH added to LT waitlist demonstrated an incremental growth, 60.6% in 2004 versus 83.2% in 2015 (p < 0.01). Among the liver transplant recipients with NASH, the proportion represented by the BB cohort increased from 56.3% in 2004 to 80.0% in 2015 (p < 0.01). Conclusions: We report rising rates of waitlist registration and LT for the indication of NASH. More importantly, the BB sub-cohort was mainly responsible for these alarming trends.

View details for PubMedID 28936399
Optimizing the Nutritional Support of Adult Patients in the Setting of Cirrhosis. Nutrients Perumpail, B. J., Li, A. A., Cholankeril, G., Kumari, R., Ahmed, A. 2017; 9 (10)
Abstract

The aim of this work is to develop a pragmatic approach in the assessment and management strategies of patients with cirrhosis in order to optimize the outcomes in this patient population.A systematic review of literature was conducted through 8 July 2017 on the PubMed Database looking for key terms, such as malnutrition, nutrition, assessment, treatment, and cirrhosis. Articles and studies looking at associations between nutrition and cirrhosis were reviewed.An assessment of malnutrition should be conducted in two stages: the first, to identify patients at risk for malnutrition based on the severity of liver disease, and the second, to perform a complete multidisciplinary nutritional evaluation of these patients. Optimal management of malnutrition should focus on meeting recommended daily goals for caloric intake and inclusion of various nutrients in the diet. The nutritional goals should be pursued by encouraging and increasing oral intake or using other measures, such as oral supplementation, enteral nutrition, or parenteral nutrition.Although these strategies to improve nutritional support have been well established, current literature on the topic is limited in scope. Further research should be implemented to test if this enhanced approach is effective.

View details for PubMedID 29027963
An Overview of Dietary Interventions and Strategies to Optimize the Management of Non-Alcoholic Fatty Liver Disease. Diseases (Basel, Switzerland) Perumpail, B. J., Cholankeril, R., Yoo, E. R., Kim, D., Ahmed, A. 2017; 5 (4)
Abstract

Aim: To investigate the efficacy of lifestyle adjustment strategies as a preventive measure and/or treatment of obesity-related non-alcoholic fatty liver disease in adults. Method: A systematic review of literature through 1 July 2017 on the PubMed Database was performed. A comprehensive search was conducted using key terms, such as non-alcoholic fatty liver disease (NAFLD), combined with lifestyle intervention, diet, and exercise. All of the articles and studies obtained from the search were reviewed. Redundant literature was excluded. Results: Several types of dietary compositions and exercise techniques were identified. Most studies concluded and recommended reduction in the intake of saturated and trans fatty acids, carbohydrates, and animal-based protein, and increased intake of polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs), plant-based proteins, antioxidants, and other nutrients was recommended. The Mediterranean and Paleo diet both seem to be promising schemes for NAFLD patients to follow. Exercise was also encouraged, but the type of exercise did not affect its efficacy as a NAFLD treatment when the duration is consistent. Conclusions: Although these different dietary strategies and exercise regimens can be adopted to treat NAFLD, current literature on the topic is limited in scope. Further research should be conducted to truly elucidate which lifestyle adjustments individually, and in combination, may facilitate patients with obesity-related NAFLD.

View details for PubMedID 29065499
Significantly Higher Mortality Following Liver Transplantation Among Patients Aged 70 Years and Older. Progress in transplantation (Aliso Viejo, Calif.) Sharma, M., Ahmed, A., Wong, R. J. 2017; 27 (3): 225–31
Abstract

The age of liver transplantation recipients in the United States is steadily increasing. However, the impact of age on liver transplant outcomes has demonstrated contradictory results.We aim to evaluate the impact of age on survival following liver transplantation among US adults.Using data from the United Network for Organ Sharing registry, we retrospectively evaluated all adults undergoing liver transplantation from 2002 to 2012 stratified by age (aged 70 years and older vs aged <70 years), presence of hepatocellular carcinoma, and hepatitis C virus status. Overall survival was evaluated with Kaplan-Meier methods and multivariate Cox proportional hazards models.Compared to patients aged <70 years, those aged 70 years and older had significantly lower 5-year survival following transplantation among all groups analyzed (hepatocellular carcinoma: 59.9% vs 68.6%, P < .01; nonhepatocellular carcinoma: 61.2% vs 74.2%, P < .001; hepatitis C: 60.7% vs 69.0%, P < .01; nonhepatitis C: 62.6% vs 78.5%, P < .001). On multivariate regression, patients aged 70 years and older at time of transplantation was associated with significantly higher mortality compared to those aged <70 years (hazards ratio: 1.67; 95% confidence interval: 1.48-1.87; P < .001).The age at the time of liver transplantation has continued to increase in the United States. However, patients aged 70 years and older had significantly higher mortality following liver transplantation. These observations are especially important given the aging cohort of patients with chronic liver disease in the United States.

View details for PubMedID 29187098
Timing of Hepatitis C Virus Treatment in Liver Transplant Candidates in the Era of Direct-acting Antiviral Agents. Journal of clinical and translational hepatology Cholankeril, G., Joseph-Talreja, M., Perumpail, B. J., Liu, A., Yoo, E. R., Ahmed, A., Goel, A. 2017; 5 (4): 363–67
Abstract

Chronic hepatitis C virus (HCV) infection remains the leading indication for liver transplantation (LT) in the United States. While most patients with chronic HCV infection remain asymptomatic, up to one-third develop progressive liver disease resulting in cirrhosis. LT is often the only curative treatment once significant hepatic decompensation develops. However, antiviral therapy for HCV infection has advanced markedly in the past 5 years with the discovery and approval of direct-acting antiviral agents. These new regimens are well tolerated, of short duration and highly effective, unlike the traditional treatment with pegylated-interferon and ribavirin. As achieving sustained virological response becomes increasingly attainable for a majority of HCV-infected patients, concerns have been raised regarding the optimal timing of treatment for HCV infection in the setting of end-stage liver disease and during the peri-transplant period. On one hand, HCV treatment may improve hepatic function and negate the need for LT in some, which is crucial given the scarcity of donor organs and mortality on the waiting list in certain regions. On the other hand, HCV treatment may result in lowering the priority for LT without improving quality of life, thereby delaying potentially curative LT surgery. This review evaluates the evidence supporting the use of direct-acting antiviral agents in the period before and following LT.

View details for PubMedID 29226102
Clinical epidemiology and disease burden of nonalcoholic fatty liver disease. World journal of gastroenterology Perumpail, B. J., Khan, M. A., Yoo, E. R., Cholankeril, G., Kim, D., Ahmed, A. 2017; 23 (47): 8263–76
Abstract

Nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma (HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type II diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear to experience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.

View details for PubMedID 29307986

View details for PubMedCentralID PMC5743497
Subclinical Hypothyroidism and Low-Normal Thyroid Function Are Associated With Nonalcoholic Steatohepatitis and Fibrosis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D., Kim, W., Joo, S. K., Bae, J. M., Kim, J. H., Ahmed, A. 2017
Abstract

Variations in level of thyroid-stimulating hormone (TSH) within the reference range of thyroid hormone could have negative health effects. We evaluated the effect of plasma TSH levels within the euthyroid range on the severity of histological damage associated with nonalcoholic fatty liver disease (NAFLD).We performed a cross-sectional study of 425 subjects with biopsy-proven NAFLD (mean age, 53 years; 52% male) who participated in the Boramae NAFLD study from January 2013 to January 2017. Each subject underwent an anthropometric assessment and laboratory and clinical evaluations. Of the subjects, 282 were assigned to a strict to normal thyroid function group (plasma level of TSH, 0.4 to 2.5 mIU/L). Patients with low thyroid function were assigned to groups of subclinical hypothyroidism (plasma level of TSH above 4.5 mIU/L within a normal thyroid hormone level; n=59) or low-normal thyroid function (higher plasma TSH level [2.5 to 4.5 mIU/L] within a normal thyroid hormone level; n=84). Multivariate logistic regression analysis was used to identify factors independently associated with nonalcoholic steatohepatitis (NASH) and advanced fibrosis.NASH and advanced fibrosis were found in higher percentages of subjects with low thyroid function vs strict-normal thyroid function (52.4% vs 37.2% for NASH and 21.0% vs 10.6% for advanced fibrosis; P < .01). Among subjects with low thyroid function, a higher proportion of patients with subclinical hypothyroidism had NASH and associated advanced fibrosis vs patients with low-normal thyroid function (57.6% vs 48.8% for NASH and 25.4% vs 17.9% for advanced fibrosis; P < .01). Subjects with low thyroid function had more extensive hepatic steatosis with greater severity of balloon degeneration and fibrosis. In multivariate analyses, low thyroid function was significantly associated with NASH (odds ratio, 1.61; 95% CI, 1.04-2.50; P = .035) and advanced fibrosis (odds ratio, 2.23; 95% CI, 1.18-4.23; P = .014). Risks of NASH and advanced fibrosis increased significantly with plasma concentration of TSH (Ptrend <.05 for each).Subclinical hypothyroidism and low-normal thyroid function are independent predictors of NASH and advanced fibrosis, confirming the relationship between these diseases. ClinicalTrials.gov, Number: NCT02206841.

View details for PubMedID 28823829
Short Sleep Duration Is Associated With Abnormal Serum Aminotransferase Activities and Nonalcoholic Fatty Liver Disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Kim, D., Kim, H. J., Kushida, C. A., Heo, N. Y., Ahmed, A., Kim, W. R. 2017
View details for PubMedID 28882688
Hepatic encephalopathy: what the multidisciplinary team can do. Journal of multidisciplinary healthcare Liu, A., Yoo, E. R., Siddique, O., Perumpail, R. B., Cholankeril, G., Ahmed, A. 2017; 10: 113-119
Abstract

Hepatic encephalopathy (HE) is a complex disease requiring a multidisciplinary approach among specialists, primary care team, family, and caregivers. HE is currently a diagnosis of exclusion, requiring an extensive workup to exclude other possible etiologies, including mental status changes, metabolic, infectious, traumatic, and iatrogenic causes. The categorization of HE encompasses a continuum, varying from the clinically silent minimal HE (MHE), which is only detectable using psychometric tests, to overt HE, which is further divided into four grades of severity. While there has been an increased effort to create fast and reliable methods for the detection of MHE, screening is still underperformed due to the lack of standardization and efficient methods of diagnosis. The management of HE requires consultation from various disciplines, including hepatology, primary care physicians, neurology, psychiatry, dietician/nutritionist, social workers, and other medical and surgical subspecialties based on clinical presentation and clear communication among these disciplines to best manage patients with HE throughout their course. The first-line therapy for HE is lactulose with or without rifaximin. Following the initial episode of overt HE, secondary prophylaxis with lactulose and/or rifaximin is indicated with the goal to prevent recurrent episodes and improve quality of life. Recent studies have demonstrated the negative impact of MHE on quality of life and clinical outcomes. In light of all this, we emphasize the importance of screening and treating MHE in patients with liver cirrhosis, particularly through a multidisciplinary team approach.

View details for DOI 10.2147/JMDH.S118963

View details for PubMedID 28392702
The importance of a multidisciplinary approach to hepatocellular carcinoma. Journal of multidisciplinary healthcare Siddique, O., Yoo, E. R., Perumpail, R. B., Perumpail, B. J., Liu, A., Cholankeril, G., Ahmed, A. 2017; 10: 95-100
Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. The rising incidence, genetic heterogeneity, multiple etiologies, and concurrent chronic liver diseases make diagnosis, staging, and selection of treatment options challenging in patients with HCC. The best approach to optimize the management of HCC is one that utilizes a core multidisciplinary liver tumor board, consisting of hepatologists, pathologists, interventional radiologists, oncologists, hepatobiliary and transplant surgeons, nurses, and general practitioners. In most cases, HCC is diagnosed by abdominal imaging studies, preferably with a triphasic computed tomography scan of the abdomen or magnetic resonance imaging of the abdomen. Histopathological diagnosis using a guided liver biopsy may be needed in noncirrhotic patients or when radiological diagnostic criteria are not fulfilled in the setting of cirrhosis. The Barcelona Clinic Liver Cancer staging system facilitates a standardized therapeutic strategy based on the tumor burden, extent of metastasis, severity of hepatic decompensation, comorbid medical illnesses, functional status of patient, HCC-related symptoms, and preference of the patient. Treatment options include curative surgery (hepatic resection and liver transplantation) and palliative measures (radiofrequency ablation, transarterial chemoembolization, and chemotherapy with sorafenib). The role of the multidisciplinary team is crucial in promptly reconfirming the diagnosis, staging the HCC, and formulating an individualized treatment plan. In potential liver transplant candidates, timely liver transplant evaluation and coordinating bridging/downsizing treatment modalities, such as radiofrequency ablation and transarterial chemoembolization, can be time-consuming. In summary, a multidisciplinary team approach provides a timely, individualized treatment plan, which can vary from curative surgery in patients with early-stage HCC to palliative/hospice care in patients with metastatic HCC. In most tertiary care centers in the US, a multidisciplinary liver tumor board has become the standard of care and a key component of best practice protocol for patients with HCC.

View details for DOI 10.2147/JMDH.S128629

View details for PubMedID 28360525
Indications for antiviral therapy for chronic hepatitis B in pregnant mothers. BMJ case reports Yoo, E. R., Perumpail, R. B., Cholankeril, G., Ahmed, A. 2016; 2016
Abstract

The use of antiviral therapy for chronic hepatitis B virus (HBV) infection in the setting of pregnancy needs to be individualised based on limited data. We report a case of a 34-year-old Korean-American woman with a history of pregnancy with emergent caesarean section due to prolonged labour in the setting of HBV e-antigen (HBeAg) positive chronic HBV with a pretreatment baseline HBV DNA level of 110000 000 million copies per mL. Her first delivery was complicated by mother-to-child transmission (MTCT) of HBV infection to her daughter despite standard active and passive immunoprophylaxis. Our case report highlights an important clinical decision-making step regarding the timing of antiviral therapy in the management of chronic HBV in pregnant women with high risk of MTCT.

View details for DOI 10.1136/bcr-2016-217232

View details for PubMedID 27852658
The Value of Cure Associated with Treating Treatment-naive Chronic Hepatitis C Genotype 1: Are the New All Oral Regimens Good Value to Society? Liver international Younossi, Z. M., Park, H., Dieterich, D., Saab, S., Ahmed, A., Gordon, S. C. 2016
Abstract

All-oral regimens are associated with high cure rates in hepatitis C virus-genotype 1 (HCV-GT1) patients. Our aim was to assess the value of cure to the society for treating HCV infection.Markov model for HCV-GT1 projected long-term health outcomes, life years, and quality-adjusted life years (QALYs) gained. The model compared second-generation triple (sofosbuvir+pegylated interferon+ribavirin [PR] and simeprevir+PR) and all-oral (ledipasvir/sofosbuvir and ombitasvir+paritaprevir/ritonavir+dasabuvir±ribavirin) therapies with no treatment. Sustained virological response rates were based on Phase III RCTs. We assumed that 80% and 95% of HCV-GT1 patients were eligible for second-generation triple and all-oral regimens. Transition probabilities, utility and mortality were based on literature review. The value of cure was calculated by the difference in the savings from the economic gains associated with additional QALYs.Model estimated 1.52 million treatment-naïve HCV-GT1 patients in the US. Treating all eligible HCV-GT1 patients with second-generation triple and all-oral therapies resulted in 3.2 million and 4.8 million additional QALYs gained compared to no treatment respectively. Using $50,000 as value of QALY, these regimens lead to savings of $185 billion and $299 billion; costs of these regimens were $109 billion and $128 billion. The value of cure with second-generation triple and all-oral regimens was $55 billion and $111 billion, when we conservatively assumed only drug costs. Cost savings were greater for HCV-GT1 patient cured with cirrhosis compared to patients without cirrhosis.The recent evolution of regimens for HCV GT1 has increased efficacy and value of cure.

View details for DOI 10.1111/liv.13298

View details for PubMedID 27804195
Lower rates of receiving model for end-stage liver disease exception and longer time to transplant among nonalcoholic steatohepatitis hepatocellular carcinoma. Liver transplantation Young, K., Aguilar, M., Gish, R., Younossi, Z., Saab, S., Bhuket, T., Liu, B., Ahmed, A., Wong, R. J. 2016; 22 (10): 1356-1366
Abstract

Receiving Model for End-Stage Liver Disease (MELD) exception status for hepatocellular carcinoma (HCC) improves wait-list survival and probability of liver transplantation (LT). We aim to evaluate etiology-specific disparities in MELD exception, LT wait-list times, and post-LT outcomes among patients with HCC listed for LT. Using United Network for Organ Sharing 2004-2013 data, we evaluated adults (age > 18 years) with HCC secondary to hepatitis C virus (HCV), nonalcoholic steatohepatitis (NASH), alcoholic cirrhosis (EtOH), hepatitis B virus (HBV), combined EtOH/HCV, and combined HBV/HCV. Multivariate regression models evaluated etiology-specific odds of active exception, probability of receiving LT, and post-LT survival. In total, 10,887 HCC patients were listed for LT from 2004 to 2013. Compared with HCV-HCC patients (86.8%), patients with NASH-HCC (67.7%), and EtOH-HCC (64.4%) had a lower proportion with active MELD exception (P < 0.001). On multivariate regression, NASH-HCC and EtOH-HCC patients had significantly lower odds of active MELD exception compared with HCV-HCC (NASH-HCC-odds ratio [OR], 0.73; 95% confidence interval [CI], 0.58-0.93; P = 0.01; EtOH-HCC-OR, 0.72; 95% CI, 0.59-0.89; P = 0.002). Compared with HCV-HCC patients, NASH-HCC (HR, 0.83; 95% CI 0.76-0.90; P < 0.001), EtOH-HCC (HR, 0.88; 95% CI 0.81-0.96; P = 0.002), and EtOH/HCV-HCC (HR, 0.92; 95% CI 0.85-0.99; P = 0.03) were less likely to receive LT if they had active exception. Without active exception, these discrepancies were more significant (NASH-HCC-HR, 0.22; 95% CI, 0.18-0.27; P < 0.001; EtOH-HCC-HR, 0.22; 95% CI, 0.18-0.26; P < 0.001; EtOH/HCV-HCC-HR, 0.26; 95% CI, 0.22-0.32; P < 0.001). In conclusion, among US adults with HCC listed for LT, patients with NASH-HCC, EtOH-HCC, and EtOH/HCV-HCC were significantly less likely to have active MELD exception compared with HCV-HCC, and those without active exception had a lower likelihood of receiving LT. More research is needed to explore why NASH-HCC patients were less likely to have active MELD exception. Liver Transplantation 22 1356-1366 2016 AASLD.

View details for DOI 10.1002/lt.24507

View details for PubMedID 27348270
Task-shifting - A practical strategy to improve the global access to treatment for chronic hepatitis C INTERNATIONAL JOURNAL OF NURSING STUDIES Yoo, E. R., Perumpail, R. B., Cholankeril, G., Jayasekera, C. R., Ahmed, A. 2016; 62: 168-169
View details for DOI 10.1016/j.ijnurstu.2016.07.023

View details for Web of Science ID 000384869200016

View details for PubMedID 27497192
Assessment of cost of innovation versus the value of health gains associated with treatment of chronic hepatitis C in the United States: The quality-adjusted cost of care. Medicine Younossi, Z. M., Park, H., Dieterich, D., Saab, S., Ahmed, A., Gordon, S. C. 2016; 95 (41)
Abstract

New direct-acting antiviral (DAA) therapy has dramatically increased cure rates for patients infected with hepatitis C virus (HCV), but has also substantially raised treatment costs.The aim of this analysis was to evaluate the therapeutic benefit and net costs (i.e. efficiency frontier) and the quality-adjusted cost of care associated with the evolution of treatment regimens for patients with HCV genotype 1 in the United States.A decision-analytic Markov model.Published literature and clinical trial data.Life Time.Third-party payer.This study compared four approved regimens in treatment-naïve genotype 1 chronic hepatitis C patients, including pegylated interferon and ribavirin (PR), first generation triple therapy (boceprevir + PR and telaprevir + PR), second generation triple therapy (sofosbuvir + PR and simeprevir + PR) and all-oral DAA regimens (ledipasvir/sofosbuvir and ombitasvir + paritaprevir/ritonavir + dasabuvir ± ribavirin).Quality-adjusted cost of care (QACC). QACC was defined as the increase in treatment cost minus the increase in the patient's quality-adjusted life years (QALYs) when valued at $50,000 per QALY.All-oral therapy improved the average sustained virologic response (SVR) rate to 96%, thereby offsetting the high drug acquisition cost of $85,714, which resulted in the highest benefit based on the efficiency frontier. Furthermore, while oral therapies increased HCV drug costs by $48,350, associated QALY gains decreased quality-adjusted cost of care by $14,120 compared to dual therapy. When the value of a QALY was varied from $100,000 to $300,000, the quality adjusted cost of care compared to dual therapy ranged from - $21,234 to - $107,861, - $89,007 to - $293,130, - $176,280 to - $500,599 for first generation triple, second generation triple, and all-oral therapies, respectively. Primary efficacy and safety measurements for drug regimens were sourced from clinical trials data rather than a real-world setting. Factors such as individual demographic characteristics, comorbidities and alcohol consumption of the individual patients treated may alter disease progression but were not captured in this analysis.New DAA treatments provide short-term and long-term clinical and economic value to society.Gilead Sciences, Inc.

View details for PubMedID 27741116
Effectiveness and tolerability of simeprevir and sofosbuvir in nontransplant and post-liver transplant patients with hepatitis C genotype 1. Alimentary pharmacology & therapeutics Lutchman, G., Nguyen, N. H., Chang, C. Y., Ahmed, A., Daugherty, T., Garcia, G., Kumari, R., Gupta, S., Doshi, D., Nguyen, M. H. 2016; 44 (7): 738-746
Abstract

Hepatitis C virus genotype 1a (HCV-1a), prior treatment, cirrhosis and post-transplant status are historically associated with poor treatment responses. The new oral direct-acting agents appear to be effective and safe in these patients.To evaluate the effectiveness and tolerability of simeprevir and sofosbuvir in a diverse real-life cohort of patients, including difficult-to-treat patients.We conducted a retrospective cohort study in 198 consecutive patients with hepatitis C genotype 1 (148 nontransplant, 50 post transplant), who were treated with simeprevir and sofosbuvir for 12 weeks between December 2013 and December 2014. Primary outcome was sustained virological response with undetectable HCV RNA 12 weeks after completion of therapy (SVR12). Risk factors evaluated for lack of SVR12 included HCV 1a (vs. 1b), prior treatment (vs. none), and cirrhosis (vs. no cirrhosis).SVR12 rates were similar in non- and post-transplant settings, 82% and 88%, respectively. There were no significant differences in adverse events in patients regardless of cirrhosis or transplant status. On multivariate analysis also inclusive of gender and liver transplant status, negative predictors of SVR12 were having at least 2 or 3 risk factors (OR 0.30, 95% CI 0.10-0.87, P = 0.027 or 0.29, 95% CI 0.09-0.85, P = 0.025, respectively).Simeprevir and sofosbuvir combination is a safe and effective regimen for the treatment of non- and post-transplant patients with traditional risk factors for poor treatment response, unless more than 2 difficult-to-treat risk factors are present.

View details for DOI 10.1111/apt.13761

View details for PubMedID 27506182
Underutilization of Living Donor Liver Transplantation in the United States: Bias against MELD 20 and Higher. Journal of clinical and translational hepatology Perumpail, R. B., Yoo, E. R., Cholankeril, G., Hogan, L., Deis, M., Concepcion, W. C., Bonham, C. A., Younossi, Z. M., Wong, R. J., Ahmed, A. 2016; 4 (3): 169-174
Abstract

Background and Aims: Utilization of living donor liver transplantation (LDLT) and its relationship with recipient Model for End-Stage Liver Disease (MELD) needs further evaluation in the United States (U.S.). We evaluated the association between recipient MELD score at the time of surgery and survival following LDLT. Methods: All U.S. adult LDLT recipients with MELD < 25 were evaluated using the 1995-2012 United Network for Organ Sharing registry. Survival following LDLT was stratified into three MELD categories (MELD < 15 vs. MELD 15-19 vs. MELD 20-24) and evaluated using Kaplan-Meier methods and multivariate Cox proportional hazards models. Results: Overall, 2,258 patients underwent LDLT. Compared to patients with MELD < 15, overall 5-year survival following LDLT was similar among patients with MELD 15-19 (80.9% vs. 80.3%, p = 0.77) and MELD 20-24 (81.2% vs. 80.3%, p = 0.73). When compared to patients with MELD < 15, there was no significant difference in long-term post-LDLT survival among those with MELD 15-19 (HR: 1.11, 95% CI: 0.85-1.45, p = 0.45) and a non-significant trend towards lower survival in patients with MELD 20-24 (HR: 1.28, 95% CI: 0.91-1.81, p = 0.16). Only 14% of LDLTs were performed in patients with MELD 20-24 and the remaining 86% in patients with MELD < 20. Conclusion: LDLT is underutilized in patients with MELD 20 and higher.

View details for PubMedID 27777886
Disparities in Liver Transplantation Resulting From Variations in Regional Donor Supply and Multiple Listing Practices. Clinical gastroenterology and hepatology Cholankeril, G., Yoo, E. R., Perumpail, R. B., Younossi, Z. M., Ahmed, A. 2016
View details for DOI 10.1016/j.cgh.2016.08.036

View details for PubMedID 27609705
Nonalcoholic Fatty Liver Disease: Epidemiology, Natural History, and Diagnostic Challenges. Hepatology Cholankeril, G., Perumpail, R. B., Pham, E. A., Ahmed, A., Harrison, S. A. 2016; 64 (3): 954-?
View details for DOI 10.1002/hep.28719

View details for PubMedID 27388553
Chronic Hepatitis B Is Associated with Higher Inpatient Resource Utilization and Mortality Versus Chronic Hepatitis C. Digestive diseases and sciences Cholankeril, G., Perumpail, R. B., Hu, M., Skowron, G., Younossi, Z. M., Ahmed, A. 2016; 61 (9): 2505-2515
Abstract

Chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infections remain one of the leading causes of chronic liver disease and hepatocellular carcinoma. Healthcare initiatives for chronic viral hepatitis to facilitate early diagnosis and linkage to care in an effort to reduce inpatient resource utilization associated with late diagnosis and end-stage liver disease have been partially successful.Our objective was to determine the impact of liver-related complications from chronic HBV and HCV infections on inpatient cost of care, length of stay, and mortality.Using the Healthcare Cost and Utilization Project, National Inpatient Sample (HCUP-NIS), we studied the impact of chronic HBV and HCV infections on inpatient healthcare system following hospitalizations from 2003 to 2012.Of the 79,185,729 million hospitalizations among adult patients in the USA from 2003 to 2012, 143,896 (0.18 %) hospitalizations were HBV related and 1,073,269 (1.36 %) hospitalizations HCV related. HBV hospitalizations had a higher inpatient mortality (OR 1.34; 95 % CI 1.30, 1.38), median cost of care per hospitalization (+$2100.33; 95 % CI 1982.53, 2217.53), and increased length of hospitalization stay (+0.64 days; 95 % CI 0.60, 0.68; p < 0.01) compared to HCV.Despite higher per case resource utilization following hospitalization, HBV-infected patients demonstrate a lower inpatient survival in comparison with chronic HCV infection. These disparate observations underscore the need for early diagnosis of chronic HBV infection in at-risk population and prompt linkage to care.

View details for DOI 10.1007/s10620-016-4160-z

View details for PubMedID 27084385
Long-term outcomes of lung transplant recipients with hepatitis C infection: a retrospective study of the US transplant registry ALIMENTARY PHARMACOLOGY & THERAPEUTICS Koenig, A., Stepanova, M., Saab, S., Ahmed, A., Wong, R., Younossi, Z. M. 2016; 44 (3): 271-278
Abstract

Chronic hepatitis C patients in need of a lung transplant are often considered ineligible due to their infection.To assess the association of hepatitis C virus (HCV) infection with long-term outcomes of lung transplants.From the Scientific Registry of Transplant Recipients (1995-2011), we selected all adults with and without HCV infection who underwent lung transplantation.A total of 17 762 lung transplant recipients were included (55.5% bilateral). Of those, 319 (1.83%) had positive HCV serology. The HCV-positive recipients were 1.6 years younger, less Caucasian and more African-American, and had a significantly higher rate of co-infection with hepatitis B virus (all P < 0.001). Post-transplant patients were discharged alive at similar rates regardless of HCV status: 88.4% in HCV+ vs. 90.3% in HCV- (P = 0.25). The mortality rates were also similar at 1 and 2 years after transplantation (20.7% in HCV+ vs. 19.2% in HCV- and 31.6% in HCV+ vs. 28.9% in HCV-, respectively; both P > 0.05), but at post-transplant year 3 year, mortality rate in HCV+ became significantly higher (42.5% vs. 36.4%, P = 0.04) and remained higher for the duration of the follow-up (mean 9.1 years, max 18.4 years). In multivariate survival analysis, after adjustment for confounders, being HCV+ was associated with higher mortality: adjusted hazard ratio 1.24 (1.04-1.46), P = 0.01. No association of HCV infection with time to graft loss was found (P = 0.92).Chronic HCV infection is associated with a moderate increase in post-lung transplant mortality. Treatment of HCV in lung transplant recipients may, therefore, result in improvement of post-transplant outcomes.

View details for DOI 10.1111/apt.13693

View details for PubMedID 27279496
Hepatitis C Treatment Delivery Mandates Optimizing Available Health Care Human Resources A Case for Task Shifting JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Jayasekera, C. R., Arora, S., Ahmed, A. 2016; 315 (18): 1947-1948
View details for DOI 10.1001/jama.2016.1993

View details for Web of Science ID 000375461100009

View details for PubMedID 27163981
Real-World Outcomes of Ledipasvir/Sofosbuvir in Treatment-Naive Patients With Hepatitis C AMERICAN JOURNAL OF MANAGED CARE Younossi, Z. M., Park, H., Gordon, S. C., Ferguson, J. R., Ahmed, A., Dieterich, D., Saab, S. 2016; 22 (6): SP205-SP211
Abstract

Studies of hepatitis C virus (HCV) regimens have documented substantially reduced effectiveness in sustained virologic response (SVR) in the context of real-world clinical practice compared with clinical trials. Real-world and clinical trial SVR and cost-per-SVR data have not been reported for the all-oral, peginterferon-free and ribavirin (RBV)-free ledipasvir/sofosbuvir (LDV/SOF) regimen. Our objective was to compare the rates of SVR achievement and cost per SVR between pooled data from clinical studies of LDV/SOF and from real-world clinical practice.Data were derived from the Hepatitis C Therapeutic Registry and Research Network (HCV-TARGET), a real-world, multicenter, prospective, observational study; and from the TRIO Network, a retrospective database of HCV-treated patients. The 1-year cost per SVR was calculated as the total cost of an SVR ([cost of treatment regimen, adverse events, and monitoring costs] per SVR) during the first year of treatment.After 12 weeks, the SVR rates obtained in real-world studies ranged from 94% to 98%, comparing favorably with the SVRs achieved in the ION-1 and ION-3 trials (94% and 95%-99% with 8 and 12 weeks of RBV-free therapy, respectively). A single SVR, on average, cost $84,989 among patients enrolled in the ION-3 trial, with higher costs ($101,204) among patients with compensated cirrhosis compared with noncirrhotic patients ($81,668). In the pooled TARGET/TRIO population, the average cost of an SVR was $84,770, with costs of $101,380 and $81,368 in patients with compensated cirrhosis and patients without cirrhosis, respectively.Unlike the results obtained with prior HCV regimens, this study suggests that similar SVR rates are achieved with LDV/SOF in clinical trial-based studies and real-world studies. Further, achieving an SVR in real-world clinical practice was not associated with excess costs.

View details for Web of Science ID 000376178900006

View details for PubMedID 27266950
Trends in Liver Transplantation in Hepatitis C Virus-Infected Persons, United States EMERGING INFECTIOUS DISEASES Perumpail, R. B., Wong, R. J., Liu, A., Jayasekera, C. R., Dieterich, D. T., Younossi, Z. M., Ahmed, A. 2016; 22 (3): 565-567
View details for DOI 10.3201/eid2203.151650

View details for Web of Science ID 000371192100041

View details for PubMedID 26889625

View details for PubMedCentralID PMC4766894
Hepatitis E virus infection in the liver transplant recipients: Clinical presentation and management. World journal of hepatology Aggarwal, A., Perumpail, R. B., Tummala, S., Ahmed, A. 2016; 8 (2): 117-122
Abstract

Hepatitis E virus (HEV) is an emerging pathogen and an increasingly recognized cause of graft hepatitis, especially in the post-orthotopic liver transplantation immunocompromised population. The exact incidence and prevalence of HEV infection in this population remains unclear but is certainly greater than historical estimates. Identifying acute HEV infection in this population is imperative for choosing the right course of management as it is very difficult to distinguish histologically from acute rejection on liver biopsy. Current suggested approach to manage acute HEV involves modifying immunosuppression, especially discontinuing calcineurin inhibitors which are the preferred immunosuppressive agents post-orthotopic liver transplantation. The addition of ribavirin monotherapy has shown promising success rates in clearing HEV infection and is used commonly in reported cases.

View details for DOI 10.4254/wjh.v8.i2.117

View details for PubMedID 26807207

View details for PubMedCentralID PMC4716527
Treatment strategies for chronic hepatitis C prior to and following liver transplantation. World journal of hepatology Perumpail, R. B., Hahambis, T. A., Aggarwal, A., Younossi, Z. M., Ahmed, A. 2016; 8 (1): 69-73
Abstract

Hepatitis C virus (HCV)-related liver disease is the leading indication for liver transplantation (LT) worldwide. However, HCV is an independent predictor of lower survival following LT, and recurrence of HCV post-LT is virtually universal. The historic standard of care during the interferon era of HCV therapy was expectant management-initiation of antiviral therapy in the setting of documented disease progression following LT. With the advent of new direct acting antiviral (DAA) therapies for HCV, the paradigm of expectant treatment for recurrent HCV infection post-LT is shifting. The safety, tolerability, and efficacy of DAAs, even among the sickest patients with advanced liver disease, enables treatment of HCV in the pre-transplant setting among LT waitlist registrants. Finally, emerging data are supportive of preemptive therapy with DAAs in liver transplant recipients as the preferred approach. Expectant management of HCV following LT can rarely be justified in the modern era of HCV therapy.

View details for DOI 10.4254/wjh.v8.i1.69

View details for PubMedID 26783422

View details for PubMedCentralID PMC4705454
A New Standard of Care? Standard Dose Sofosbuvir in an HCV-Infected Liver Transplant Recipient Undergoing Hemodialysis DIGESTIVE DISEASES AND SCIENCES Perumpail, R. B., Wong, R. J., Pham, E. A., Higgins, J. P., Daugherty, T. J., Ahmed, A. 2016; 61 (1): 39-41
View details for DOI 10.1007/s10620-015-3756-z

View details for Web of Science ID 000367609300008
Task-shifting - A practical strategy to improve the global access to treatment for chronic hepatitis C. International journal of nursing studies Yoo, E. R., Perumpail, R. B., Cholankeril, G., Jayasekera, C. R., Ahmed, A. 2016; 62: 168–69
View details for PubMedID 27497192
Direct Acting Antivirals in Patients with Chronic Hepatitis C and Down Syndrome. Case reports in infectious diseases Yoo, E. R., Perumpail, R. B., Cholankeril, G., Ahmed, A. 2016; 2016: 2605302-?
Abstract

Patients with Down syndrome who received blood transfusions, likely in conjunction with cardiothoracic surgery for congenital heart disease and prior to the implementation of blood-donor screening for hepatitis C virus infection, face a substantial risk of acquiring the infection. In the past, interferon-based therapy for chronic hepatitis C infection in patients with Down syndrome was noted to have lower efficacy and potentially higher risk of adverse effects. Recently, the treatment for chronic hepatitis C has been revolutionized with the introduction of interferon-free direct acting antivirals with favorable safety, tolerability, and efficacy profile. Based on our experiences, the newly approved sofosbuvir-based direct acting antiviral therapy is well tolerated and highly efficacious in this subpopulation of hepatitis C virus infected patients with Down syndrome.

View details for PubMedID 27847658
High prevalence of hepatic fibrosis in the setting of coexisting diabetes and hepatic steatosis: A case for selective screening in the general population? HEPATOLOGY Ahmed, A., Perumpail, R. B., Harrison, S. A. 2016; 63 (1): 20-22
View details for DOI 10.1002/hep.28277

View details for PubMedID 26452752
A New Standard of Care? Standard Dose Sofosbuvir in an HCV-Infected Liver Transplant Recipient Undergoing Hemodialysis. Digestive diseases and sciences Perumpail, R. B., Wong, R. J., Pham, E. A., Higgins, J. P., Daugherty, T. J., Ahmed, A. 2016; 61 (1): 39–41
View details for PubMedID 26082077
Future Therapy for Hepatitis B Virus: Role of Immunomodulators. Current hepatology reports Pham, E. A., Perumpail, R. B., Fram, B. J., Glenn, J. S., Ahmed, A., Gish, R. G. 2016; 15 (4): 237-244
Abstract

Although currently available therapies for chronic hepatitis B virus infection can suppress viremia and provide long-term benefits for patients, they do not lead to a functional cure for most patients. Advances in our understanding of the virus-host interaction and the recent remarkable success of immunotherapy in cancer offer new and promising strategies for developing immune modulators that may become important components of a total therapeutic approach to hepatitis B, some of which are now in clinical development. Among the immunomodulatory agents currently being investigated to combat chronic HBV are toll-like receptor agonists, immune checkpoint inhibitors, therapeutic vaccines, and engineered T cells. The efficacy of some immune modulatory therapies is compromised by high viral antigen levels. Cutting edge strategies, including RNA interference and CRISPR/Cas9, are now being studied that may ultimately be shown to have the capacity to lower viral antigen levels sufficiently to substantially increase the efficacy of these agents. The current advances in therapies for chronic hepatitis B are leading us toward the possibility of a functional cure.

View details for PubMedID 27917363
Trends in Liver Transplantation Multiple Listing Practices Associated With Disparities in Donor Availability: An Endless Pursuit to Implement the Final Rule. Gastroenterology Cholankeril, G., Perumpail, R. B., Tulu, Z., Jayasekera, C. R., Harrison, S. A., Hu, M., Esquivel, C. O., Ahmed, A. 2016; 151 (3): 382–86.e2
View details for PubMedID 27456386
The impact of viral hepatitis-related hepatocellular carcinoma to post-transplant outcomes JOURNAL OF VIRAL HEPATITIS Younossi, Z. M., Stepanova, M., Saab, S., Ahmed, A., Lam, B., Srishord, M., Venkatesan, C., Wai, H., Henry, L. 2016; 23 (1): 53-61
View details for DOI 10.1111/jvh.12449

View details for Web of Science ID 000367401000008
Advances in cirrhosis: Optimizing the management of hepatic encephalopathy. World journal of hepatology Liu, A., Perumpail, R. B., Kumari, R., Younossi, Z. M., Wong, R. J., Ahmed, A. 2015; 7 (29): 2871-2879
Abstract

Hepatic encephalopathy (HE) is a major complication of cirrhosis resulting in significant socioeconomic burden, morbidity, and mortality. HE can be further subdivided into covert HE (CHE) and overt HE (OHE). CHE is a subclinical, less severe manifestation of HE and requires psychometric testing for diagnosis. Due to the time consuming screening process and lack of standardized diagnostic criteria, CHE is frequently underdiagnosed despite its recognized role as a precursor to OHE. Screening for CHE with the availability of the Stroop test has provided a pragmatic method to promptly diagnose CHE. Management of acute OHE involves institution of lactulose, the preferred first-line therapy. In addition, prompt recognition and treatment of precipitating factors is critical as it may result in complete resolution of acute episodes of OHE. Treatment goals include improvement of daily functioning, evaluation for liver transplantation, and prevention of OHE recurrence. For secondary prophylaxis, intolerance to indefinite lactulose therapy may lead to non-adherence and has been identified as a precipitating factor for recurrent OHE. Rifaximin is an effective add-on therapy to lactulose for treatment and prevention of recurrent OHE. Recent studies have demonstrated comparable efficacy of probiotic therapy to lactulose use in both primary prophylaxis and secondary prophylaxis.

View details for DOI 10.4254/wjh.v7.i29.2871

View details for PubMedID 26692331

View details for PubMedCentralID PMC4678373
Update on hepatitis C: Direct-acting antivirals. World journal of hepatology Seifert, L. L., Perumpail, R. B., Ahmed, A. 2015; 7 (28): 2829-2833
Abstract

Hepatitis C virus (HCV) was discovered 26 years ago. For decades, interferon-based therapy has been the mainstay of treatment for HCV. Recently, several direct-acting antivirals (DAAs) have been approved for treatment of HCV-infected patients and to help combat the virus. These drugs have revolutionized the management of HCV as all-oral regimens with favorable side effect profiles and superior rates of sustained virological response. Emerging real-world data are demonstrating results comparable to registration trials for DAA agents. Suddenly, the potential for eradicating HCV is on the horizon.

View details for DOI 10.4254/wjh.v7.i28.2829

View details for PubMedID 26668694
Task-Shifting: An Approach to Decentralized Hepatitis C Treatment in Medically Underserved Areas DIGESTIVE DISEASES AND SCIENCES Jayasekera, C. R., Perumpail, R. B., Chao, D. T., Pham, E. A., Aggarwal, A., Wong, R. J., Ahmed, A. 2015; 60 (12): 3552-3557
Abstract

Despite the availability of safe and effective direct-acting antiviral drugs (DAAs), the vast majority of patients with chronic hepatitis C (HCV) in the USA remain untreated, in part due to lack of access to specialist providers.To determine the effectiveness of DAA-based treatment in medically underserved areas in California, in a healthcare model dependent on task-shifting--wherein a visiting hepatologist assesses patients for treatment eligibility, but subsequent routine follow-up evaluation of patients prescribed treatment is devolved to a part-time licensed vocational nurse under remote supervision of the hepatologist.We retrospectively determined rates of sustained virologic response 12 weeks after treatment completion (SVR-12), adverse events, and treatment discontinuations in patients who received sofosbuvir-based DAA regimens between December 2013 and November 2014.Despite limited specialist provider involvement in medically underserved areas, all but two of 58 patients completed treatment, and 88 % of patients achieved the curative endpoint of undetectable HCV RNA 12 weeks after completing treatment (sustained virologic response, SVR-12). Almost 80 % of patients with cirrhosis and 85 % of patients with prior treatment experience achieved SVR-12.Treatment effectiveness with sofosbuvir-based regimens in medically underserved areas utilizing task-shifting from a specialist to a mid-level provider is comparable to those achieved in pivotal clinical trials for these regimens, and to “real-world” experiences of tertiary care centers in the USA.

View details for DOI 10.1007/s10620-015-3911-6

View details for Web of Science ID 000364563600011
Advances in alcoholic liver disease: An update on alcoholic hepatitis. World journal of gastroenterology Liang, R., Liu, A., Perumpail, R. B., Wong, R. J., Ahmed, A. 2015; 21 (42): 11893-11903
Abstract

Alcoholic hepatitis is a pro-inflammatory chronic liver disease that is associated with high short-term morbidity and mortality (25%-35% in one month) in the setting of chronic alcohol use. Histopathology is notable for micro- and macrovesicular steatosis, acute inflammation with neutrophil infiltration, hepatocellular necrosis, perivenular and perisinusoidal fibrosis, and Mallory hyaline bodies found in ballooned hepatocytes. Other findings include the characteristic eosinophilic fibrillar material (Mallory's hyaline bodies) found in ballooned hepatocytes. The presence of focal intense lobular infiltration of neutrophils is what typically distinguishes alcoholic hepatitis from other forms of hepatitis, in which the inflammatory infiltrate is primarily composed of mononuclear cells. Management consists of a multidisciplinary approach including alcohol cessation, fluid and electrolyte correction, treatment of alcohol withdrawal, and pharmacological therapy based on the severity of the disease. Pharmacological treatment for severe alcoholic hepatitis, as defined by Maddrey's discriminant factor ≥ 32, consists of either prednisolone or pentoxifylline for a period of four weeks. The body of evidence for corticosteroids has been greater than pentoxifylline, although there are higher risks of complications. Recently head-to-head trials between corticosteroids and pentoxifylline have been performed, which again suggests that corticosteroids should strongly be considered over pentoxifylline.

View details for DOI 10.3748/wjg.v21.i42.11893

View details for PubMedID 26576078

View details for PubMedCentralID PMC4641111
Nonalcoholic Fatty Liver Disease Review: Diagnosis, Treatment, and Outcomes CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Ahmed, A., Wong, R. J., Harrison, S. A. 2015; 13 (12): 2062-2070
View details for DOI 10.1016/j.cgh.2015.07.029

View details for PubMedID 26226097
Pathogenesis of hepatocarcinogenesis in non-cirrhotic nonalcoholic fatty liver disease: Potential mechanistic pathways. World journal of hepatology Perumpail, R. B., Liu, A., Wong, R. J., Ahmed, A., Harrison, S. A. 2015; 7 (22): 2384-2388
Abstract

Although hepatocellular carcinoma (HCC) primarily arises in the background of liver cirrhosis, the development of HCC in nonalcoholic fatty liver disease (NAFLD) without cirrhosis is increasingly recognized. The pathogenesis of NAFLD associated non-cirrhotic HCC is distinct from that of cirrhotic HCC because the metabolic syndrome (MS) along with obesity and insulin resistance (IR) underlie several unique mechanisms that promote tumorigenesis. IR associated with MS, NAFLD, and type 2 diabetes mellitus lead to the release of multiple pro-inflammatory cytokines, including tumor necrosis factor alpha, interleukin-6, leptin and resistin, as well as decreased amounts of adiponectin. These processes favor the development of hepatic steatosis and inflammation within the liver, which precede HCC development. Nevertheless, further investigation is necessary to elucidate the determinants for development of HCC in patients with NAFLD in the absence of cirrhosis.

View details for DOI 10.4254/wjh.v7.i22.2384

View details for PubMedID 26464753
HCV infection is associated with lower survival in simultaneous liver kidney transplant recipients in the United States CLINICAL TRANSPLANTATION Perumpail, R. B., Wong, R. J., Scandling, J. D., Ha, L. D., Todo, T., Bonham, C. A., Saab, S., Younossi, Z. M., Ahmed, A. 2015; 29 (10): 920-926
Abstract

The frequency of simultaneous liver kidney transplantation (SLKT) has been increasing over the past decade. Hepatitis C virus (HCV) infection is the most common indication for liver transplantation in the United States. Given the rising prevalence of HCV-related SLKT, it is important to understand the impact of HCV in this patient population.We conducted a retrospective cohort study using data from the United Network for Organ Sharing registry to assess adult patients undergoing SLKT in the United States from 2003 to 2012. Patient survival following SLKT was assessed using Kaplan-Meier methods and multivariate Cox proportional hazards models.Patients infected with non-HCV have significantly lower survival following SLKT compared to non-HCV patients at three (three-yr survival: 71.0% vs. 78.9%, p < 0.01) and five yr (five-yr survival: 61.4% vs. 72.5%, p < 0.01). The results of multivariate regression analyses demonstrated that patients infected with HCV had significantly lower survival following SLKT than patients with non-HCV disease (HR 1.41, 95% CI, 1.19-1.67, p < 0.001). In addition, lower post-SLKT survival was noted among patients with diabetes (HR 1.34, 95% CI, 1.13-1.58, p < 0.001) and hepatocellular carcinoma (HR 1.60, 95% CI, 1.17-2.18, p < 0.01).Hepatitis C infection is associated with lower patient survival following SLKT.

View details for DOI 10.1111/ctr.12598

View details for PubMedID 26205329
Hepatocellular Carcinoma in the Setting of Non-cirrhotic Nonalcoholic Fatty Liver Disease and the Metabolic Syndrome: US Experience. Digestive diseases and sciences Perumpail, R. B., Wong, R. J., Ahmed, A., Harrison, S. A. 2015; 60 (10): 3142-3148
Abstract

Type 2 diabetes mellitus, obesity, and the metabolic syndrome (MS) have been growing in prevalence in the USA and are independent risk factors for the development of hepatocellular carcinoma (HCC). Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the MS, with or without nonalcoholic steatohepatitis (NASH) can predispose to HCC in the absence of cirrhosis or advanced fibrosis. Nevertheless, the US literature investigating non-cirrhotic HCC in the setting of NAFLD/NASH and MS is lacking.To describe a retrospective case series of patients who developed HCC without cirrhosis in the setting of NAFLD/NASH or features of the MS.We identified NAFLD/NASH-associated HCC cases arising in the absence of cirrhosis between January 2010 and September 2012 from a tumor board database at Brooke Army Medical Center (BAMC).Of 44 cases of HCC reviewed, six cases of non-cirrhotic HCC associated with NAFLD/NASH and/or MS were identified. Only one patient underwent partial hepatectomy with curative intent. The other five might have been candidates for potential curative partial hepatectomy or liver transplantation had they been diagnosed earlier.Our case series highlights the development of NAFLD/NASH and MS-associated HCC in the absence of cirrhosis in the US population and raises the important question of HCC screening for this at-risk group.

View details for DOI 10.1007/s10620-015-3821-7

View details for PubMedID 26250831
Fatal Accelerated Cirrhosis after Imported HEV Genotype 4 Infection EMERGING INFECTIOUS DISEASES Perumpail, R. B., Ahmed, A., Higgins, J. P., So, S. K., Cochran, J. L., Drobeniuc, J., Mixson-Hayden, T. R., Teo, C. 2015; 21 (9): 1679-1681
View details for DOI 10.3201/eid2109.150300

View details for Web of Science ID 000359894000036

View details for PubMedID 26291424

View details for PubMedCentralID PMC4550159
Advances in hepatocellular carcinoma: Nonalcoholic steatohepatitis-related hepatocellular carcinoma. World journal of hepatology Khan, F. Z., Perumpail, R. B., Wong, R. J., Ahmed, A. 2015; 7 (18): 2155-2161
Abstract

An increase in the prevalence of obesity and diabetes mellitus has been associated with the rise in nonalcoholic fatty liver disease (NAFLD). Two-thirds of the obese and diabetic populations are estimated to develop NAFLD. Currently, NAFLD is the most common etiology for chronic liver disease globally. The clinical spectrum of NAFLD ranges from simple steatosis, an accumulation of fat greater than 5% of liver weight, to nonalcoholic steatohepatitis (NASH), a more aggressive form with necroinflammation and fibrosis. Among the patients who develop NASH, up to 20% may advance to cirrhosis and are at risk for complications of end-stage liver disease. One of the major complications observed in patients with NASH-related cirrhosis is hepatocellular carcinoma (HCC), which has emerged as the sixth most common cancer and second leading etiology of cancer-related deaths worldwide. The incidence of HCC in the United States alone has tripled over the last three decades. In addition, emerging data are suggesting that a small proportion of patients with NAFLD may be at higher risk for HCC in the absence of cirrhosis - implicating obesity and diabetes mellitus as potential risk factors for HCC.

View details for DOI 10.4254/wjh.v7.i18.2155

View details for PubMedID 26328027
Acute Liver Failure: A Potential Complication of Antithyroid Medication Use. Digestive diseases and sciences Chou, C., Wong, R. J., Higgins, J. P., Perumpail, R. B., Ahmed, A. 2015; 60 (7): 1924-1927
View details for DOI 10.1007/s10620-014-3389-7

View details for PubMedID 25366145
The impact of pretransplant hepatic encephalopathy on survival following liver transplantation LIVER TRANSPLANTATION Wong, R. J., Aguilar, M., Gish, R. G., Cheung, R., Ahmed, A. 2015; 21 (7): 873-880
Abstract

Hepatic encephalopathy (HE) is a surrogate marker of liver disease severity, and more severe HE is associated with higher mortality among patients with chronic liver disease. However, whether severity of HE at the time of liver transplantation (LT) directly impacts post-LT survival or whether this suspected mortality linkage is due to more severe liver disease and subsequently higher rates of post-LT infection is not well defined. Using population-based data from the 2003 to 2013 United Network for Organ Sharing registry, we evaluated the impact of HE at the time of LT on post-LT survival among adults in the United States. Survival was stratified by HE severity (none, grade 1-2, grade 3-4) and Model for End-Stage Liver Disease score and was evaluated using Kaplan-Meier methods and multivariate Cox proportional hazards models. From 2003 to 2013, 59,937 patients underwent LT (36.1%, no HE; 53.8%, grade 1-2 HE; 10.2%, grade 3-4 HE). Compared to no HE, patients with grade 3-4 HE had significantly lower overall post-LT survival (1-year, 82.5% versus 90.3%; P < 0.001; 5-year, 69.1% versus 74.4%; P < 0.001). On multivariate regression, grade 3-4 HE was independently associated with lower overall post-LT survival (HR, 1.27; 95% CI, 1.17-1.39; P < 0.001). However, the increased mortality associated with HE is observed primarily within the first year following LT and was a reflection of higher rates of infection-related deaths among patients with more severe HE. In conclusion, grade 3-4 HE at the time of LT is associated with lower post-LT survival, with a proposed direct or indirect association of more severe HE before LT with increased rates of post-LT infections. Increased awareness and vigilance toward treating HE before LT and more aggressive monitoring and treatment for infections in the perioperative setting may improve LT outcomes. Liver Transpl 21:873-880, 2015. © 2015 AASLD.

View details for DOI 10.1002/lt.24153

View details for PubMedID 25902933
Elevated alpha-fetoprotein: differential diagnosis - hepatocellular carcinoma and other disorders. Clinics in liver disease Wong, R. J., Ahmed, A., Gish, R. G. 2015; 19 (2): 309-323
Abstract

The incidence of cirrhosis-related hepatocellular carcinoma (HCC) is rising. Curative surgical options are available; outcomes are acceptable with early diagnosis. Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) and des-gamma-carboxy prothrombin (DCP) are HCC risk markers. A high or increasing serum biomarker level can be predictive of the eventual development of HCC, large tumor size, advanced stage, extrahepatic metastases, portal vein thrombosis, and postoperative HCC recurrence. Based on FDA guidelines for HCC risk assessment, clinicians can consider using either the combination of AFP-L3 with DCP, or the combination of AFP-L3 with AFP and DCP.

View details for DOI 10.1016/j.cld.2015.01.005

View details for PubMedID 25921665
Elevated Alpha-Fetoprotein Differential Diagnosis - Hepatocellular Carcinoma and Other Disorders CLINICS IN LIVER DISEASE Wong, R. J., Ahmed, A., Gish, R. G. 2015; 19 (2): 309-?
Abstract

The incidence of cirrhosis-related hepatocellular carcinoma (HCC) is rising. Curative surgical options are available; outcomes are acceptable with early diagnosis. Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) and des-gamma-carboxy prothrombin (DCP) are HCC risk markers. A high or increasing serum biomarker level can be predictive of the eventual development of HCC, large tumor size, advanced stage, extrahepatic metastases, portal vein thrombosis, and postoperative HCC recurrence. Based on FDA guidelines for HCC risk assessment, clinicians can consider using either the combination of AFP-L3 with DCP, or the combination of AFP-L3 with AFP and DCP.

View details for DOI 10.1016/j.cld.2015.01.005

View details for Web of Science ID 000354664500007

View details for PubMedID 25921665
Diabetes Mellitus, and Not Obesity, Is Associated with Lower Survival Following Liver Transplantation DIGESTIVE DISEASES AND SCIENCES Wong, R. J., Cheung, R., Perumpail, R. B., Holt, E. W., Ahmed, A. 2015; 60 (4): 1036-1044
Abstract

The impact of obesity on survival following liver transplantation is unclear, and existing studies report conflicting results. Our current study aims to further delineate the impact of obesity using population-based registry data from the USA.All US adult liver transplant recipients from 2003 to 2012 were evaluated using the United Network for Organ Sharing registry. The impact of obesity on survival following liver transplantation was further stratified into class I obesity [body mass index (BMI) 30.0-34.9 kg/m(2)], class II obesity (BMI 35.0-39.9 kg/m(2)), and class III obesity (BMI ≥ 40 kg/m(2)) and evaluated using Kaplan-Meier methods and multivariate Cox proportional hazards models.Overall, 57,255 patients with chronic liver disease underwent liver transplantation, among which 32.9 % had BMI ≥ 30 kg/m(2). While patients in all obesity classes had similar survival to patients with BMI 18.0-24.9 kg/m(2), the presence of concurrent diabetes mellitus resulted in significantly lower post-transplant survival. After multivariate regression, post-transplant survival in patients with class II obesity (HR 0.97; 95 % CI 0.89-1.05) or class III obesity (HR 0.99; 95 % CI 0.90-1.09) was not significantly lower than patients with BMI 18.0-24.9 kg/m(2), but diabetes mellitus was independently associated with lower post-transplant survival (HR 1.29; 95 % CI 1.21-1.36).In conclusion, obesity alone was not associated with lower post-transplant survival. However, DM, either alone or comorbid with obesity, is associated with significantly greater post-transplant mortality.

View details for DOI 10.1007/s10620-014-3469-8

View details for Web of Science ID 000354464900037

View details for PubMedID 25596720
Sofosbuvir and simeprevir combination therapy in the setting of liver transplantation and hemodialysis TRANSPLANT INFECTIOUS DISEASE Perumpail, R. B., Wong, R. J., Ha, L. D., Pham, E. A., Wang, U., Luong, H., Kumari, R., Daugherty, T. J., Higgins, J. P., Younossi, Z. M., Kim, W. R., Glenn, J. S., Ahmed, A. 2015; 17 (2): 275-278
Abstract

We report safety, tolerability, and 12-week sustained virologic response with half-standard dose sofosbuvir and standard-dose simeprevir combination therapy in a hepatitis C virus genotype 1a-infected liver transplant recipient on hemodialysis - uncharted territory for sofosbuvir-based therapy. The patient was a non-responder to prior treatment with pegylated interferon plus ribavirin. Sofosbuvir efficacy was maintained despite pill-splitting and administration of half-standard dose, 200 mg per day. No drug-drug interactions were noted with tacrolimus-based immunosuppression. Laboratory tests remained stable or improved during therapy. Our observation, if reproduced in a larger study, may lead to significant improvement in clinical outcomes and cost savings in this patient population.

View details for DOI 10.1111/tid.12348

View details for Web of Science ID 000352219400013

View details for PubMedID 25641426
Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology Wong, R. J., Aguilar, M., Cheung, R., Perumpail, R. B., Harrison, S. A., Younossi, Z. M., Ahmed, A. 2015; 148 (3): 547-555
Abstract

Nonalcoholic steatohepatitis (NASH) has been predicted to become the leading indication for liver transplantation (LT) in the United States. However, few studies have evaluated changes in the etiology of liver diseases among patients awaiting LT, and none have focused on the effects of NASH on liver transplant waitlists in the United States.We collected data from the United Network for Organ Sharing and Organ Procurement and Transplantation Network registry from 2004 through 2013, on liver transplant waitlist registrants with hepatitis C virus (HCV) infection, NASH, alcoholic liver disease (ALD), or a combination of HCV infection and ALD. We compared differences in survival within 90 days of registration (90-day survival) and probability of LT among patients with different diseases using Kaplan-Meier and multivariate logistic regression models.Between 2004 and 2013, new waitlist registrants with NASH increased by 170% (from 804 to 2174), with ALD increased by 45% (from 1400 to 2024), and with HCV increased by 14% (from 2887 to 3291); registrants with HCV and ALD decreased by 9% (from 880 to 803). In 2013, NASH became the second-leading disease among liver transplant waitlist registrants, after HCV. Patients with ALD had a significantly higher mean Model for End-Stage Liver Disease score at time of waitlist registration than other registrants. However, after multivariate adjustment, patients with ALD were less likely to die within 90 days when compared with patients with NASH (odds ratio [OR] = 0.77; 95% confidence interval [CI]: 0.67-0.89; P < .001); patients with HCV infection or HCV and ALD had similar odds for 90-day survival compared with NASH patients. Compared with patients with NASH, patients with HCV (OR = 1.45; 95% CI: 1.35-1.55; P < .001), ALD (OR = 1.15; 95% CI: 1.06-1.24; P < .001), or HCV and ALD (OR = 1.29; 95% CI: 1.18-1.42; P < .001) had higher odds for 90-day survival.Based on data from US adult LT databases, since 2004 the number of adults with NASH awaiting LTs has almost tripled. However, patients with NASH are less likely to undergo LT and less likely to survive for 90 days on the waitlist than patients with HCV, ALD, or HCV and ALD.

View details for DOI 10.1053/j.gastro.2014.11.039

View details for PubMedID 25461851
Cost-effectiveness of all-oral ledipasvir/sofosbuvir regimens in patients with chronic hepatitis C virus genotype 1 infection. Alimentary pharmacology & therapeutics Younossi, Z. M., Park, H., Saab, S., Ahmed, A., Dieterich, D., Gordon, S. C. 2015; 41 (6): 544-563
Abstract

An all-oral, pegylated interferon (pegIFN)-free and ribavirin (RBV)-free single-tablet of ledipasvir (LDV) and sofosbuvir (SOF) is now approved for the treatment of patients infected with hepatitis C virus (HCV) genotype 1.To estimate the health economic outcomes for LDV/SOF compared with current treatments in US patients infected with HCV genotype 1.A hybrid decision-tree and Markov state-transition model was developed. For a cohort of 10 000 patients, the model captured outcomes for several pairings of LDV/SOF with comparators, including long-term health outcomes, number need to treat, life-years gained, quality-adjusted life-years (QALYS) gained, incremental cost-effectiveness ratios and costs per sustained virologic response (SVR). Patients with different levels of treatment experience and different cirrhosis stages were included.LDV/SOF decreased the number of advanced liver disease cases by 0-93% compared with current regimens or no treatment in treatment-naïve patients. In treatment-experienced [pegIFN plus ribavirin (PR) or protease inhibitor (PI) + PR] patients, treatment with LDV/SOF decreased the incidence of advanced liver disease complications in most of the cases analysed, except SOF + SMV. For all patient sub-cohorts, LDV/SOF was associated with the lowest 1-year costs per SVR and, with regard to lifetime incremental costs per QALY gained, was either dominant or the most cost-effective treatment. Overall, treatment initiation at earlier stages of liver fibrosis resulted in improved health economic outcomes.LDV/SOF is associated with more favourable short- and long-term health economic outcomes compared with current therapies for patients across all levels of treatment experience and cirrhosis stages.

View details for DOI 10.1111/apt.13081

View details for PubMedID 25619871
Recurrent Hepatocellular Carcinoma and Poorer Overall Survival in Patients Undergoing Left-sided Compared With Right-sided Partial Hepatectomy. Journal of clinical gastroenterology Valenzuela, A., Ha, N. B., Gallo, A., Bonham, C., Ahmed, A., Melcher, M., Kim, L. H., Esquivel, C., Concepcion, W., Ayoub, W. S., Lutchman, G. A., Daugherty, T., Nguyen, M. H. 2015; 49 (2): 158-164
Abstract

We aimed to determine the incidence and predictors of recurrent hepatocellular carcinoma (HCC) after partial hepatectomy.Liver transplantation is the preferred treatment for selected patients with HCC, but access to donor organs is limited. Partial hepatectomy is another accepted treatment option; however, postoperative recurrence is frequently observed.This is a retrospective cohort study of 107 consecutive patients who underwent partial hepatectomy for HCC between January 1993 and February 2011 at a US University Medical Center. Study endpoints were recurrent HCC, death, loss to follow-up, or last visit without HCC.The study cohort was 78% male with a median age of 61 years and 59% Asians. A total of 50 patients developed recurrent HCC (46.7%) after a median follow-up of 12 (1 to 69) months postresection. Recurrent HCC was significantly higher in patients with left-sided resection (41% at year 1, 54% at year 2, 62% at year 3, 81% at year 4, and 90% at year 5) compared with right-sided resection (18% at year 1, 34% at year 2, 36% at year 3, 44% at year 4, and 72% at year 5). In multivariate Cox proportional hazards model also inclusive of anatomic resection and TNM stage 3/4, left-sided resection was significantly associated with increased HCC recurrence (hazard ratio, 2.13; P=0.02; 95% confidence interval, 1.08-4.2) compared with right-sided resection.HCC recurrence rate is higher among those undergoing left-sided resection: 54% at year 2 and 81% at year 4. Liver transplantation should be considered in patients who are at high risk for recurrence.

View details for DOI 10.1097/MCG.0000000000000144

View details for PubMedID 24804988
Hepatic Encephalopathy Is Associated With Significantly Increased Mortality Among Patients Awaiting Liver Transplantation LIVER TRANSPLANTATION Wong, R. J., Gish, R. G., Ahmed, A. 2014; 20 (12): 1454-1461
Abstract

The prioritization of liver transplantation (LT) for patients with end-stage liver disease uses the Model for End-Stage Liver Disease (MELD), which attempts to identify the sickest patients and thereby those who are in greatest need for LT. Hepatic encephalopathy (HE) is not included in MELD, and severity of liver disease and risk of wait-list removal or wait-list death may be underestimated by MELD in patients with HE. Using United Network for Organ Sharing registry data, we evaluated the impact of HE on 90-day wait-list survival among adult LT wait-list registrants in the United States from 2003 to 2012. Survival was stratified by HE severity (none, grade 1-2, grade 3-4) and MELD. There were 84,947 new LT wait-list registrants during the study period; 36.8% had no HE, 57.4% had grade 1-2 HE, and 5.9% had grade 3-4 HE. Ninety-day wait-list mortality was significantly higher among patients with grade 3-4 HE compared with patients with grade 1-2 HE or no HE (24.4% versus 6.8% versus 3.5%; P < 0.001). When stratified by MELD, patients with grade 3-4 HE had 90-day wait-list mortality similar to that of nonencephalopathic patients with MELD scores 6-7 points higher. With the multivariate Cox proportional hazards model, patients with grade 3-4 HE had 66% greater risk of 90-day mortality than patients without HE (hazard ratio = 1.66, 95% CI = 1.45-1.90; P < 0.001). The inclusion of HE severity in MELD improved the area under receiver operating curve for predicting 90-day wait-list survival from 0.6508 to 0.6863. In conclusion, grade 3-4 HE at time of wait-list registration significantly increases 90-day wait-list mortality independent of MELD score. Incorporating HE in the assessment of LT priority may improve prognostication of liver disease severity and prioritization for LT.

View details for DOI 10.1002/lt.23981

View details for Web of Science ID 000345619600004
Hepatic encephalopathy is associated with significantly increased mortality among patients awaiting liver transplantation. Liver transplantation Wong, R. J., Gish, R. G., Ahmed, A. 2014; 20 (12): 1454-1461
Abstract

The prioritization of liver transplantation (LT) for patients with end-stage liver disease uses the Model for End-Stage Liver Disease (MELD), which attempts to identify the sickest patients and thereby those who are in greatest need for LT. Hepatic encephalopathy (HE) is not included in MELD, and severity of liver disease and risk of wait-list removal or wait-list death may be underestimated by MELD in patients with HE. Using United Network for Organ Sharing registry data, we evaluated the impact of HE on 90-day wait-list survival among adult LT wait-list registrants in the United States from 2003 to 2012. Survival was stratified by HE severity (none, grade 1-2, grade 3-4) and MELD. There were 84,947 new LT wait-list registrants during the study period; 36.8% had no HE, 57.4% had grade 1-2 HE, and 5.9% had grade 3-4 HE. Ninety-day wait-list mortality was significantly higher among patients with grade 3-4 HE compared with patients with grade 1-2 HE or no HE (24.4% versus 6.8% versus 3.5%; P < 0.001). When stratified by MELD, patients with grade 3-4 HE had 90-day wait-list mortality similar to that of nonencephalopathic patients with MELD scores 6-7 points higher. With the multivariate Cox proportional hazards model, patients with grade 3-4 HE had 66% greater risk of 90-day mortality than patients without HE (hazard ratio = 1.66, 95% CI = 1.45-1.90; P < 0.001). The inclusion of HE severity in MELD improved the area under receiver operating curve for predicting 90-day wait-list survival from 0.6508 to 0.6863. In conclusion, grade 3-4 HE at time of wait-list registration significantly increases 90-day wait-list mortality independent of MELD score. Incorporating HE in the assessment of LT priority may improve prognostication of liver disease severity and prioritization for LT.

View details for DOI 10.1002/lt.23981

View details for PubMedID 25155379
Long Term Trends and Racial/Ethnic Disparities in the Prevalence of Obesity JOURNAL OF COMMUNITY HEALTH Wong, R. J., Chou, C., Ahmed, A. 2014; 39 (6): 1150-1160
Abstract

Obesity is an epidemic associated with higher rates of hypertension, diabetes, and cardiovascular diseases. However, significant racial disparities in the prevalence of obesity have been reported. To evaluate racial disparities and trends in the prevalence of obesity and obesity-related diseases. A population-based retrospective cohort study utilized data from the 1985 to 2011 California Behavioral Risk Factor Survey. Trends in obesity prevalence were stratified by age, sex, race/ethnicity, and socioeconomic factors. Multivariate logistic regression models evaluated independent predictors of obesity. The prevalence of obesity in significantly increased from 1985 to 2011 (8.6 vs. 22.8%, p < 0.001). This increase was seen among men and women, and among all race/ethnic, age, and socioeconomic groups. Hypertension and diabetes also increased during this time period (hypertension 20.7-35.9%; diabetes 4.2-11.2%). Obesity prevalence was highest in blacks and Hispanics, and lowest in Asians (blacks 33.3%; Hispanics 28.8%; Asians 9.0%; p < 0.001). Obesity prevalence was associated with lower education level, lower income, and unemployment status. After adjustments for age, sex, co morbidities, and surrogates of socioeconomic status, the increased risk of obesity in blacks and Hispanics persisted (blacks OR 1.51; Hispanics OR 1.18), whereas Asians were less likely to be obese (OR 0.37). While the overall prevalence of obesity increased from 1985 to 2011, significant racial/ethnic disparities in obesity have developed, with the highest prevalence seen in blacks and Hispanics, and the lowest seen in Asians.

View details for DOI 10.1007/s10900-014-9870-6

View details for Web of Science ID 000344606900018

View details for PubMedID 24715435
Cost-effectiveness analysis of sofosbuvir plus peginterferon/ribavirin in the treatment of chronic hepatitis C virus genotype 1 infection ALIMENTARY PHARMACOLOGY & THERAPEUTICS Saab, S., Gordon, S. C., Park, H., Sulkowski, M., Ahmed, A., Younossi, Z. 2014; 40 (6): 657-675
Abstract

Sofosbuvir, an oral NS5B nucleotide polymerase inhibitor, is indicated for the treatment of patients infected with hepatitis C virus (HCV).To evaluate the long-term health economic outcomes of sofosbuvir + pegylated interferon alfa/ribavirin (pegIFN/RBV) compared with current treatments in patients infected with HCV genotype 1 in the US.A decision-analytic Markov model was developed to estimate health outcomes, number needed to treat and short-term and long-term economic outcomes, including incremental cost-effectiveness ratios and cost per sustained virological response (SVR), for several sofosbuvir-comparator regimen pairings for a cohort of 10 000 patients. It considered three patient cohorts: treatment-naïve, treatment-experienced and treatment-naïve human immunodeficiency virus (HIV) co-infected. Subgroup analyses were conducted for treatment-naïve patients with and without cirrhosis.Reductions in the incidence of new cases of liver-disease complications with sofosbuvir + pegIFN/RBV compared with pegIFN/RBV, boceprevir + pegIFN/RBV, telaprevir + pegIFN/RBV and simeprevir + pegIFN/RBV were 64-82%, 50-68%, 43-58% and 33-56%, respectively. Sofosbuvir + pegIFN/RBV was typically associated with the lowest 1-year cost per SVR. When considering the lifetime incremental cost per quality-adjusted life-year gained, sofosbuvir + pegIFN/RBV was the most cost-effective treatment option assessed. Sofosbuvir + pegIFN/RBV generally dominated (less costly and more effective than) boceprevir + pegIFN/RBV, telaprevir + pegIFN/RBV and simeprevir + pegIFN/RBV.Sofosbuvir + pegIFN/RBV yields more favourable future health and economic outcomes than current treatment regimens for patients across all levels of treatment experience and cirrhosis stage, as well as for individuals with or without HIV co-infection.

View details for DOI 10.1111/apt.12871

View details for Web of Science ID 000340559900008

View details for PubMedID 25065960
Mutations in HBV DNA polymerase associated with nucleos(t)ide resistance are rare in treatment-naive patients. Clinical gastroenterology and hepatology Vutien, P., Trinh, H. N., Garcia, R. T., Nguyen, H. A., Levitt, B. S., Nguyen, K., da Silveira, E., Daugherty, T., Ahmed, A., Garcia, G., Lutchman, G. A., Nguyen, M. H. 2014; 12 (8): 1363-1370
Abstract

Prior studies have detected hepatitis B virus (HBV) DNA polymerase mutations in treatment-naive patients. However, most of these studies used either direct polymerase chain reaction sequencing, which detects these mutations with low levels of sensitivity, or patient cohorts that were not well-characterized. We investigated the prevalence of HBV mutations in DNA polymerase by using a line probe assay.In a prospective, cross-sectional study, we enrolled 198 treatment-naive patients with chronic hepatitis B (52.5% male; mean age, 41 years) from February 2009 to May 2011 from 3 gastroenterology and liver clinics in Northern California. Exclusion criteria included infection with hepatitis C or D viruses or human immunodeficiency virus. All patients completed a questionnaire (to determine demographics, history of liver disease, prior treatments, family medical history, drug and alcohol use, and environmental risk factors for hepatitis) that was administered by a research coordinator; mutations in HBV DNA polymerase were detected by using the INNO-LiPA HBV DR v.3 assay.Most patients were Vietnamese (48.5%) or Chinese (36.4%) and were infected with HBV genotypes B (67.5%) or C (24.2%). Mutations in HBV DNA polymerase were found in 2 patients (1%), rtI233V (n = 1) and rtM250M/L (n = 1).In a multicenter prospective study of treatment-naive patients with chronic hepatitis B, we detected mutations in HBV DNA polymerase in only 1%. Because of the low prevalence of these mutations and the uncertain clinical significance of such quasispecies, routine HBV DNA polymerase mutation analysis cannot be recommended before initiation of antiviral therapy for treatment-naive patients with chronic hepatitis B. The analysis requires further molecular and clinical studies.

View details for DOI 10.1016/j.cgh.2013.11.036

View details for PubMedID 24342744
Mutations in HBV DNA Polymerase Associated With Nucleos(t)ide Resistance Are Rare in Treatment-naive Patients. Clinical gastroenterology and hepatology Vutien, P., Trinh, H. N., Garcia, R. T., Nguyen, H. A., Levitt, B. S., Nguyen, K., da Silveira, E., Daugherty, T., Ahmed, A., Garcia, G., Lutchman, G. A., Nguyen, M. H. 2014; 12 (8): 1363-1370
View details for DOI 10.1016/j.cgh.2013.11.036

View details for PubMedID 24342744
Hepatitis C Virus Infection and Coronary Artery Disease Risk: A Systematic Review of the Literature DIGESTIVE DISEASES AND SCIENCES Wong, R. J., Kanwal, F., Younossi, Z. M., Ahmed, A. 2014; 59 (7): 1586-1593
Abstract

While hepatitis C virus (HCV) infection has been implicated in increasing the risk of coronary artery disease (CAD), conflicting reports exist regarding this association. We performed a systematic review to further investigate this association.We conducted a PubMed search of original research articles from January 1, 1995 to June 30, 2013 to identify case-control and cohort studies evaluating the association between HCV and CAD using keyword terms ["hepatitis c" or "HCV"] and ["coronary artery disease" or "heart disease" or "atherosclerosis."] The primary CAD-related endpoints included myocardial infarction, congestive heart failure, need for coronary artery bypass grafting, or transluminal percutaneous coronary angioplasty. Binary outcomes are reported as odds ratios (OR) with 95 % confidence interval (CI).We identified five studies (four cohort studies and one case-control study) that met our inclusion criteria. A significant association between HCV and CAD was demonstrated in one cohort study (adjusted HR 1.27; 95 % CI 1.22-1.31). One cohort study demonstrated a decreased risk of CAD associated with HCV (adjusted OR 0.74; 95 % CI 0.71-0.76). The remaining studies did not find a significant association between HCV and risk of CAD.The current systematic review demonstrates that the association between HCV and CAD remains unclear. We need more large, long-term cohort studies with clear definitions of patient population and endpoints to better ascertain the association between HCV and CAD.

View details for DOI 10.1007/s10620-014-3222-3

View details for Web of Science ID 000338344500036

View details for PubMedID 24894512
Combination of racial/ethnic and etiology/disease-specific factors is associated with lower survival following liver transplantation in African Americans: an analysis from UNOS/OPTN database CLINICAL TRANSPLANTATION Wong, R. J., Ahmed, A. 2014; 28 (7): 755-761
Abstract

Higher rates of hepatitis C virus (HCV) recurrence and lower response to HCV antiviral therapy contribute to the lower post-liver transplantation (LT) survival among African Americans with HCV. The current study aims to evaluate race/ethnicity-specific and etiology-specific factors contributing to lower post-LT survival among African Americans in the USA. The 2002-2012 United Network for Organ Sharing registry was utilized to evaluate race/ethnicity-specific post-LT survival among patients with HCV, hepatocellular carcinoma (HCC), alcoholic liver disease (ALD), non-alcoholic steatohepatitis, and cryptogenic cirrhosis. From 2002 to 2012, HCV was the leading indication for LT. While African Americans accounted for 9.5% of all LT during this period, they had the lowest overall and etiology-specific five-yr post-LT survival. On multivariate Cox proportional hazards modeling, African Americans had significantly lower post-LT survival compared with non-Hispanic whites among patients with HCV (HR, 1.30; 95% CI, 1.19-1.41), HCC (HR, 1.49; 95% CI, 1.25-1.79), and ALD (HR, 1.52; 95% CI, 1.19-1.94). In conclusion, African Americans had the lowest post-LT survival among patients with HCV, HCC, and ALD. Race/ethnicity and the etiology of chronic liver disease were observed to have a combined detrimental effect leading to lower survival following LT in African Americans.

View details for DOI 10.1111/ctr.12374

View details for Web of Science ID 000339100800001

View details for PubMedID 24750171
Improved survival outcomes in patients with non-alcoholic steatohepatitis and alcoholic liver disease following liver transplantation: an analysis of 2002-2012 United Network for Organ Sharing data. Clinical transplantation Wong, R. J., Chou, C., Bonham, C. A., Concepcion, W., Esquivel, C. O., Ahmed, A. 2014; 28 (6): 713-721
Abstract

There is an increasing trend of patients with hepatocellular carcinoma (HCC) and non-alcoholic fatty liver disease undergoing liver transplantation in the U.S. Our study utilized data from the 2002-2012 United Network for Organ Sharing registry to evaluate MELD era trends in U.S. liver transplantations focused on patients with non-alcoholic steatohepatitis (NASH), hepatitis C (HCV), alcoholic liver disease, and HCC. Survival outcomes were stratified by liver disease etiology and compared across time periods using Kaplan Meier and Cox proportional hazards models. Patients with NASH were more likely to be women, had higher body mass index, and higher prevalence of diabetes and cardiac disease. However, overall long term survival was significantly higher in NASH and alcoholic liver disease patients (p < 0.001). Compared to HCV, NASH patients had significantly higher post-transplantation survival (HR 0.69, 95% CI 0.63-0.77), and lower risk of graft failure (HR 0.76, 95% CI 0.69-0.83). Despite having higher body mass index and higher prevalence of diabetes and cardiac disease, NASH patients had better post-liver transplantation survival compared to patients with HCV or HCC. Patients with alcoholic liver disease also had superior survival outcomes. However, these survival differences were limited to patients without HCC that underwent liver transplantation. This article is protected by copyright. All rights reserved.

View details for DOI 10.1111/ctr.12364

View details for PubMedID 24654688
Nonalcoholic Steatohepatitis Is the Most Rapidly Growing Indication for Liver Transplantation in Patients With Hepatocellular Carcinoma in the U. S. HEPATOLOGY Wong, R. J., Cheung, R., Ahmed, A. 2014; 59 (6): 2188-2195
Abstract

Nonalcoholic steatohepatitis (NASH) is currently the third leading indication for liver transplantation (LT) in the U.S. and is predicted to become the leading indication for LT in the near future. The trends in NASH-related hepatocellular carcinoma (HCC) among LT recipients in the U.S. remain undefined. We performed a retrospective cohort study to evaluate trends in the etiology of HCC among adult LT recipients in the U.S. from 2002 to 2012, utilizing national data from the United Network for Organ Sharing registry. From 2002-2012, there were 61,868 adults who underwent LT in the U.S., including 10,061 patients HCC. The total number and proportion of HCC LT recipients demonstrated a significant increase following the implementation of the model for end stage liver disease (MELD) scoring system in 2002 (3.3%, n=143 in 2000 vs. 12.2%, n=714 in 2005 vs. 23.3%, n=1336 in 2012). The proportion of HCV-related HCC increased steadily from 2002 to 2012, and HCV remained the leading etiology of HCC throughout the MELD era (43.4% in 2002 vs. 46.3% in 2007 vs. 49.9% in 2012). NASH-related HCC also increased significantly, and NASH is the second leading etiology of HCC-related LT (8.3% in 2002 vs. 10.3% in 2007 vs. 13.5% in 2012). From 2002 to 2012, the number of patients undergoing LT for HCC secondary to NASH increased by nearly 4-fold, and the number of LT patients with HCC secondary to HCV increased by 2-fold. Conclusion: NASH is the second leading etiology of HCC leading to LT in the U.S. More importantly, NASH is currently the most rapidly growing indication for LT in patients with HCC in the U.S. (Hepatology 2013;).

View details for DOI 10.1002/hep.26986

View details for Web of Science ID 000337567100020

View details for PubMedID 24375711
Ethnic Disparities in the Association of Body Mass Index with the Risk of Hypertension and Diabetes JOURNAL OF COMMUNITY HEALTH Wong, R. J., Chou, C., Sinha, S. R., Kamal, A., Ahmed, A. 2014; 39 (3): 437-445
Abstract

Despite having lower body mass index (BMI) compared to other ethnic groups, Asians continue to develop significant metabolic diseases such as hypertension and diabetes. To evaluate the disparate association of BMI and risk of hypertension and diabetes in Asians. We retrospectively studied 150,753 adults from the 1985-2011 California Behavioral Risk Factor Survey. Trends in prevalence of obesity, hypertension, and diabetes were stratified by ethnicity. Multivariate logistic regression models evaluated the incremental effect of one unit BMI increase on risk of hypertension and diabetes and the disparate risks of hypertension and diabetes at different BMI thresholds. Asians had the lowest BMI among all groups. However, the impact of increasing BMI on risk of hypertension and diabetes was significantly greater in Asians. For each one unit increase in BMI, Asians were significantly more likely to have hypertension (OR 1.15; 95 % CI 1.13-1.18) compared to non-Hispanic whites, blacks, and Hispanics. Similar trends were seen for diabetes (Asians: OR 1.15; 95 % CI 1.13-1.18). The risk of hypertension in Asians with BMI ≥ 22 was similar to non-Hispanic whites with BMI ≥ 27 and blacks with BMI ≥ 28. The risk of diabetes in Asians with BMI ≥ 28 was similar to non-Hispanic whites with BMI ≥ 30. Despite lower overall BMI compared to other groups, weight gain in Asians is associated with significantly higher risks of hypertension and diabetes. Compared to other ethnic groups, similar risks of hypertension and diabetes are seen in Asians at much lower BMI.

View details for DOI 10.1007/s10900-013-9792-8

View details for Web of Science ID 000335392600005

View details for PubMedID 24276618
Obesity and non-alcoholic fatty liver disease: Disparate associations among Asian populations. World journal of hepatology Wong, R. J., Ahmed, A. 2014; 6 (5): 263-273
Abstract

Obesity is a global epidemic contributing to an increasing prevalence of obesity-related systemic disorders, including nonalcoholic fatty liver disease. The rising prevalence of nonalcoholic steatohepatitis (NASH) will in the near future lead to end-stage liver disease in a large cohort of patients with NASH-related cirrhosis and NASH is predicted to be a leading indication for liver transplantation in the coming decade. However, the prevalence of obesity and the progression of hepatic histological damage associated with NASH exhibit significant ethnic disparities. Despite a significantly lower body mass index and lower rates of obesity compared to other ethnic groups, Asians continue to demonstrate a significant prevalence of hypertension, diabetes, metabolic syndrome and NASH. Ethnic disparities in central adiposity and visceral fat distribution have been hypothesized to contribute to these ethnic disparities. The current review focuses on the epidemiology of obesity and NASH among Asian populations.

View details for DOI 10.4254/wjh.v6.i5.263

View details for PubMedID 24868320

View details for PubMedCentralID PMC4033284
The impact of hepatitis C burden: an evidence-based approach ALIMENTARY PHARMACOLOGY & THERAPEUTICS Younossi, Z. M., Kanwal, F., Saab, S., Brown, K. A., El-Serag, H. B., Kim, W. R., Ahmed, A., Kugelmas, M., Gordon, S. C. 2014; 39 (5): 518-531
Abstract

Infection with the hepatitis C virus (HCV) has been considered a major cause of mortality, morbidity and resource utilisation in the US. In addition, HCV is the main cause of hepatocellular cancer (HCC) in the US. Recent developments in the diagnosis and treatment of HCV, including new recommendations pertaining to screening for HCV by the Centers for Disease Control and Prevention and newer treatment regimens with high efficacy, short duration and the potential for interferon-free therapies, have energised the health care practitioners regarding HCV management.To assess the full impact of HCV burden on clinical, economic and patient-reported outcomes.An expert panel was convened to assess the full impact of HCV burden on a number of important outcomes using an evidence-based approach predicated on Grading of Recommendations Assessment, Development and Evaluation methodology. The literature was summarised, graded using an evidence-based approach and presented during the workshop. Workshop presentations were intended to review recent, relevant evidence-based literature and provide graded summary statements pertaining to HCV burden on topics including the relationships between HCV and the development of important outcomes.The associations of HCV with cirrhosis, HCC, liver-related mortality, type 2 diabetes mellitus, rheumatological diseases and quality of life impairments are supported by strong evidence. Also, there is strong evidence that sustained viral eradication of HCV can improve important outcomes such as mortality and quality of life.The current evidence suggests that HCV has been associated with tremendous clinical, economic and quality of life burden.

View details for DOI 10.1111/apt.12625

View details for Web of Science ID 000330564900007

View details for PubMedID 24461160
Primary surgical resection versus liver transplantation for transplant-eligible hepatocellular carcinoma patients. Digestive diseases and sciences Wong, R. J., Wantuck, J., Valenzuela, A., Ahmed, A., Bonham, C., Gallo, A., Melcher, M. L., Lutchman, G., Concepcion, W., Esquivel, C., Garcia, G., Daugherty, T., Nguyen, M. H. 2014; 59 (1): 183-191
Abstract

Hepatocellular carcinoma (HCC) is a leading cause of mortality worldwide. Existing studies comparing outcomes after liver transplantation (LT) versus surgical resection among transplant-eligible patients are conflicting.The purpose of this study was to compare long-term survival between consecutive transplant-eligible HCC patients treated with resection versus LT.The present retrospective matched case cohort study compares long-term survival outcomes between consecutive transplant-eligible HCC patients treated with resection versus LT using intention-to-treat (ITT) and as-treated models. Resection patients were matched to LT patients by age, sex, and etiology of HCC in a 1:2 ratio.The study included 171 patients (57 resection and 114 LT). Resection patients had greater post-treatment tumor recurrence (43.9 vs. 12.9 %, p < 0.001) compared to LT patients. In the as-treated model of the pre-model for end stage liver disease (MELD) era, LT patients had significantly better 5-year survival compared to resection patients (100 vs. 69.5 %, p = 0.04), but no difference was seen in the ITT model. In the multivariate Cox proportional hazards model, inclusive of age, sex, ethnicity, tumor stage, and MELD era (pre-MELD vs. post-MELD), treatment with resection was an independent predictor of poorer survival (HR 2.72; 95 % CI, 1.08-6.86).Transplant-eligible HCC patients who received LT had significantly better survival than those treated with resection, suggesting that patients who can successfully remain on LT listing and actually undergo LT have better outcomes.

View details for DOI 10.1007/s10620-013-2947-8

View details for PubMedID 24282054
Review article: the epidemiology and therapy of chronic hepatitis C genotypes 4, 5 and 6 ALIMENTARY PHARMACOLOGY & THERAPEUTICS Wantuck, J. M., Ahmed, A., Nguyen, M. H. 2014; 39 (2): 137-147
Abstract

The global burden of hepatitis C (HCV) infection is mostly found in Africa, the Middle East and Asia, where HCV genotypes 4, 5 and 6 are common. The literature on these genotypes is sparse and this synopsis will review characteristics of patients infected with these genotypes.To review characteristics of patients infected with HCV genotypes 4, 5 and 6.PubMed search for 'hepatitis C' AND 'genotype 4', 'hepatitis C' AND 'genotype 5', and 'hepatitis C' AND 'genotype 6' was conducted and relevant articles were reviewed.Intravenous drug use is generally responsible for HCV genotype 4 infection in developed countries, but unsafe medical practices cause most cases of HCV genotypes 4, 5 and 6 in endemic countries. The sustained virological response (SVR) rate for patients with HCV genotype 4 who receive pegylated interferon and ribavirin for 48 weeks ranges from 40% to 70% in various small studies. The SVR rate is in the 60-70% range for HCV genotype 5 and 70-80% range for HCV genotype 6 following 48 weeks with pegylated interferon and ribavirin. Preliminary data suggest that a shorter course of 24 weeks of pegylated interferon and ribavirin may be acceptable for HCV genotype 6, with an SVR rate of approximately 70%.The current standard-of-care therapy for HCV genotypes 4, 5 and 6 is pegylated interferon and ribavirin for 48 weeks. A shorter course with 24 weeks of therapy may be considered for patients with genotype 6. Newer and much more effective therapies may be forthcoming in the next few years.

View details for DOI 10.1111/apt.12551

View details for Web of Science ID 000328283900003

View details for PubMedID 24251930
Clinical Presentation and Survival of Asian and Non-Asian Patients with HCV-Related Hepatocellular Carcinoma DIGESTIVE DISEASES AND SCIENCES Yip, B., Wantuck, J. M., Kim, L. H., Wong, R. J., Ahmed, A., Garcia, G., Nguyen, M. H. 2014; 59 (1): 192-200
Abstract

Hepatitis C virus (HCV) is an important cause of hepatocellular carcinoma (HCC) in Asians; however, it is often overlooked due to the high prevalence of hepatitis B virus in Asians. This study examines HCV-related HCC in Asians.We conducted a retrospective cohort study of 792 consecutive Asian (n = 220) and non-Asian (n = 572) patients with HCV-related HCC identified at Stanford University Medical Center using International Classification of Diseases-9 diagnosis between July 1996 and June 2012.Asian patients were much older [66 (38-88) vs. 56 (31-87) years, P < 0.0001] and more likely to be female (33 vs. 19 %, P < 0.0001). A larger proportion of Asians were diagnosed with HCC within 2 years of HCV diagnosis (35 vs. 20 %, P = 0.001). Asian patients were more likely to undergo palliative therapy (46 vs. 28 %) and less likely to be listed for liver transplantation (20 vs. 48 %, P < 0.001), despite similar rates of meeting Milan criteria (52 vs. 58 %, P = 0.16). Overall, there was a trend for higher median survival rates in Asians (30 vs. 21 months, P = 0.091). Asians had higher long-term survival with palliative therapy only (5-year survival: 28 vs. 10 %, P < 0.0001); however, survival was similar among patients listed for liver transplantation.There were distinct differences in clinical presentations of Asian and non-Asian patients with HCV-related HCC. Asians with HCV-related HCC are less likely to undergo liver transplantation and more likely to have delayed HCV diagnosis. Improved strategies in HCV screening in Asians are needed, as it may lead to earlier diagnosis and treatment of HCV infection and possible prevention of HCC development.

View details for DOI 10.1007/s10620-013-2948-7

View details for Web of Science ID 000330585500030

View details for PubMedID 24282055
Both HCV and HBV are Major Causes of Liver Cancer in Southeast Asians. Journal of immigrant and minority health Lin, H., Ha, N. B., Ahmed, A., Ayoub, W., Daugherty, T. J., Lutchman, G. A., Garcia, G., Nguyen, M. H. 2013; 15 (6): 1023-1029
Abstract

The incidence of hepatocellular carcinoma (HCC) is higher in Asian Americans than in other ethnicities. While hepatitis B virus (HBV) is common, hepatitis C virus (HCV) is more prevalent in some subgroups. Our goal was to determine the etiology of liver disease associated with HCC in subgroups of Asian Americans. This was an analysis of 510 Asian HCC patients at a US medical center. Patients were identified using ICD9 diagnosis. Multivariate logistic regression was used to study predictors of HCV as the cause of HCC. Patients were Southeast Asian, Chinese, and Korean, with similar gender, age, and foreign-born status. Southeast Asians had a similar proportion of HBV- and HCV-related HCC, while Chinese and Korean patients had a higher proportion of HBV-related HCC. HCC was usually associated with HBV in Chinese and Korean patients, but both HCV and HBV were important associations in Southeast Asians.

View details for DOI 10.1007/s10903-013-9871-z

View details for PubMedID 23864445
Low incidence of hepatitis B e antigen seroconversion in patients treated with oral nucleos(t)ides in routine practice. Journal of gastroenterology and hepatology Lin, B., Ha, N. B., Liu, A., Trinh, H. N., Nguyen, H. A., Nguyen, K. K., Ahmed, A., Keeffe, E. B., Garcia, R. T., Garcia, G., Nguyen, M. H. 2013; 28 (5): 855-860
Abstract

Treatment end-point of therapy for patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) includes HBeAg seroconversion, which ranges from 15% to 22% after 1 year of oral nucleos(t)ides according to clinical trials. Our goal was to determine the incidence and predictors of HBeAg seroconversion in such patients in routine clinical practice because they may differ than reported rates.We conducted a retrospective cohort study of 333 consecutive treatment-naïve HBeAg-positive patients who were treated for CHB between 1/2000 and 6/2010 at three gastroenterology and liver clinics in the USA. Primary study end-point was HBeAg seroconversion-loss of HBeAg and antibody to HBeAg (anti-HBe) development.The majority of patients were Asian (96%). Median treatment duration prior to HBeAg seroconversion was 50 (range 26-52) weeks. Of the 333 study patients, 25% received lamivudine, 16% adefovir, 51% entecavir, and 8% tenofovir. HBeAg seroconversion at month 12 was 8.2%. On multivariate analysis inclusive of age, gender, and antiviral agents, independent predictors for HBeAg seroconversion at month 12 were hepatitis B virus DNA < 7.5 log10 IU/mL (hazard ratio [HR] = 2.59 [1.04-6.44]), P = 0.041) and alanine transaminase (ALT) > 1.5 × upper normal limit (HR = 2.86 [1.05-7.81], P = 0.040), but not the choice of nucleos(t)ides.The HBeAg seroconversion rate seen in clinical settings for oral nucleos(t)ides appears much lower than those reported in pivotal trials, especially in patients with lower ALT and higher HBV DNA levels. HBeAg-positive patients should be counseled about the high possibility of the long treatment duration required to achieve recommended treatment end-points.

View details for DOI 10.1111/jgh.12108

View details for PubMedID 23278507
Low hepatitis B envelope antigen seroconversion rate in chronic hepatitis B patients on long-term entecavir 0.5 mg daily in routine clinical practice EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY Liu, A., Ha, N. B., Lin, B., Yip, B., Trinh, H. N., Nguyen, H. A., Nguyen, K. K., Ahmed, A., Garcia, G., Nguyen, M. H. 2013; 25 (3): 338-343
Abstract

Data from registration trials with highly selective patients have shown that hepatitis B envelope antigen (HBeAg)-positive patients with chronic hepatitis B respond well to entecavir (ETV) 0.5 mg daily, with an HBeAg seroconversion rate of 21% at 12 months. However, there are varying data on the treatment outcomes of ETV 0.5 mg daily in routine clinical settings, with seroconversion rates at 12 months ranging from 8 to 48% in studies limited to 44-90 patients from centers in Asia, Europe, and South America.In the present study, we examined long-term treatment efficacy and tolerability in 136 consecutive treatment-naive HBeAg-positive chronic hepatitis B patients treated between January 2005 and January 2011 with ETV 0.5 mg daily at community clinics and tertiary centers in the USA. The primary study end point was HBeAg seroconversion.Sixty-one percent of HBeAg-positive patients were men, mean age 39 ± 12 years, median hepatitis B virus DNA 7.48 (3.7-9.8) log10 IU/ml, median alanine aminotransferase 67 (14-1077) U/l, and median treatment duration 18 (6-60) months. At months 12, 24, and 36, complete viral suppression rates were 41, 66, and 85% and HBeAg seroconversion rates were 4.8, 20, and 30%, respectively. No patients experienced adverse events or developed genotypic resistance to ETV.In clinical settings, ETV is highly tolerable and potent at suppressing hepatitis B viremia; however, the rates of HBeAg seroconversion appear to be much lower than those reported, highlighting the importance of appropriate counseling and planning for long-term therapy.

View details for DOI 10.1097/MEG.0b013e32835b3677

View details for PubMedID 23169311
Donor Diabetes Mellitus Is an Independent Risk Factor for Graft Loss in HCV Positive but Not HCV Negative Liver Transplant Recipients DIGESTIVE DISEASES AND SCIENCES Wu, Y., Ahmed, A., Kamal, A. 2013; 58 (2): 574-578
Abstract

Graft survival in HCV (hepatitis C virus) infected recipients is worse than those transplanted for other liver diseases. We studied whether several donor cardiovascular risk factors (including advanced age, smoking, hypertension, and diabetes mellitus) contribute to worse outcomes for HCV positive and HCV negative liver transplant recipients.We obtained data from the United Network for Organ Sharing on all adult liver transplants performed in the United States between January 1, 1998 and December 31, 2003. In total, 27,033 transplant cases were evaluated. Independent predictors of graft survival were determined using Cox proportional hazards regression analysis after controlling for factors previously found to be associated with differences in transplant outcomes.Donor diabetes was a strong independent risk factor for graft failure [hazard ratio (HR) = 1.20, p = 0.006] only in HCV positive recipients. Neither donor smoking status nor hypertension predicted graft loss in either cohort. Consistent with previous studies, advanced donor age, donation after cardiac death, height, and African American donor all predicted graft loss amongst both cohorts.Accounting for donor diabetes in relation to recipient HCV status in the selection of liver recipients may result in improved graft survival.

View details for DOI 10.1007/s10620-012-2345-7

View details for Web of Science ID 000315291100039

View details for PubMedID 22923335
Precore and basal core promoter mutations in Asian American patients with hepatitis B e antigen-positive chronic hepatitis B ALIMENTARY PHARMACOLOGY & THERAPEUTICS VuTien, P., Trinh, H. N., Nguyen, K., Garcia, R. T., Nguyen, H. A., Levitt, B. S., Nguyen, L., Ha, N. B., Ahmed, A., Daugherty, T., Garcia, G., Nguyen, M. H. 2013; 37 (4): 464-472
Abstract

Prior studies have shown that precore mutations abolish and basal core promoter (BCP) mutations down-regulate hepatitis B e antigen (HBeAg) production. Thus, the presence of precore and BCP mutations in HBeAg-positive patients indicates an infection with a mixed viral population of wild-type and precore and/or BCP mutant hepatitis B virus (HBV). To date, there has been limited study of the prevalence and clinical significance of precore and BCP mutations in patients with HBeAg-positive chronic hepatitis B.To determine the prevalence, predictors and clinical characteristics of mixed wild-type and precore/BCP HBV infection, through a cross-sectional study, in a US cohort of patients with chronic hepatitis B.We conducted a retrospective study of 828 chronic hepatitis B patients with HBV genotype and mutation panel testing seen at three US gastroenterology and liver clinics from June 2005 to September 2009.A majority of our patients (92.3%) were either Vietnamese or Chinese American. In the HBeAg-positive cohort, 17% of patients had precore mutations only, 28% had BCP mutations only and 5% had both BCP and precore mutations. On multivariate analyses, HBV genotype C, increasing age, lower HBV DNA level and an ALT quotient >2 were independent predictors for the presence of precore and/or BCP mutations.The current distinction and management recommendations for HBeAg-positive vs. HBeAg-negative patients with chronic hepatitis B should be reassessed. Additional biomarkers and treatment endpoints should be studied for their usefulness in predicting continued viral suppression after treatment discontinuation.

View details for DOI 10.1111/apt.12193

View details for Web of Science ID 000313891900011

View details for PubMedID 23278246
Incidence of Hepatocellular Carcinoma Among US Patients With Cirrhosis of Viral or Nonviral Etiologies CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Mair, R. D., Valenzuela, A., Ha, N. B., Ayoub, W. S., Daugherty, T., Lutchman, G. A., Garcia, G., Ahmed, A., Nguyen, M. H. 2012; 10 (12): 1412-1417
Abstract

We aimed to identify risk factors for hepatocellular carcinoma (HCC) in patients with cirrhosis in the United States. We performed a prospective study to identify associations between etiologies of cirrhosis and ethnicity with HCC incidence.We used convenience sampling to select a cohort of 379 patients with cirrhosis who visited the liver clinic at the Stanford University Medical Center from 2001 to 2009 (65% male, 75% white or Hispanic, and 20% Asian). Study end points were HCC diagnosis by histology or noninvasive criteria, liver transplantation, or last screening without HCC. Patients were followed up, with ultrasound or computed tomographic imaging analyses and measurements of serum levels of α-fetoprotein, approximately every 6 months, for a median time of 34 months (range, 6-99 mo).The etiologies of cirrhosis in the cohort were 68% hepatitis C, 7% hepatitis B, and 25% nonviral. Forty-four patients (12%) were diagnosed with HCC during the follow-up period. Patients with cirrhosis related to viral hepatitis had a statistically significantly higher incidence of HCC than those with nonviral diseases in Kaplan-Meier analysis (P = .04). There was no statistically significant difference in HCC incidence between Asian and non-Asian patients. In a multivariate Cox proportional hazards model that included age, sex, ethnicity, etiology, and Child-Pugh-Turcotte score, viral cirrhosis was associated significantly with HCC, compared with nonviral cirrhosis (hazard ratio, 3.6; 95% confidence interval, 1.3-10.1; P = .02) but Asian ethnicity was not.In a diverse cohort of patients in the United States with cirrhosis, a viral etiology of cirrhosis was associated with increased incidence of HCC, but Asian ethnicity was not. These findings indicate the importance of cirrhosis etiology in determining risk for HCC.

View details for DOI 10.1016/j.cgh.2012.08.011

View details for Web of Science ID 000312265900021

View details for PubMedID 22902757

View details for PubMedCentralID PMC3511850
Commentary: physical activity and NAFLD - cause or effect? ALIMENTARY PHARMACOLOGY & THERAPEUTICS Ahmed, A., Forrest, E. H. 2012; 36 (11-12): 1097-1098
View details for DOI 10.1111/apt.12078

View details for Web of Science ID 000310871000014

View details for PubMedID 23130768
Tenofovir Monotherapy and Tenofovir Plus Entecavir Combination as Rescue Therapy for Entecavir Partial Responders DIGESTIVE DISEASES AND SCIENCES Yip, B., Chaung, K., Wong, C. R., Trinh, H. N., Nguyen, H. A., Ahmed, A., Cheung, R., Nguyen, M. H. 2012; 57 (11): 3011-3016
Abstract

Despite high potency, a significant proportion of patients treated with entecavir achieve only partial viral suppression. Our goal was to examine the complete viral suppression rate (undetectable HBV DNA PCR levels) with alternative therapies in such patients.We retrospectively studied 42 consecutive patients with partial response to entecavir (detectable HBV DNA at ≥12 months of therapy) who were treated at three clinics with rescue therapies: entecavir + adefovir (n = 5), tenofovir (n = 6), and entecavir + tenofovir (n = 31). Antiviral resistance was excluded by negative mutation analysis and/or absence of virologic breakthrough (increase >1 log(10)IU/mL from nadir).All patients were Asian and 57 % were male with a median age of 36 (22-64) years. Only a few patients had prior exposure to lamivudine (7 %) or adefovir (7 %). Almost all patients (95 %) had positive HBeAg. Overall, the complete viral suppression rate was 79 %, and the alanine aminotransferase normalization rate was 83 % in entecavir partial responders after 6 months on rescue therapies. Cumulative complete viral suppression rates were significantly different (P = 0.0164) among the entecavir + adefovir, tenofovir, and entecavir + tenofovir treatment groups at 6 months (20 vs. 83 vs. 83 %, respectively) and 12 months (20 vs. 100 vs. 97 %). All three patients without complete viral suppression on entecavir + adefovir became aviremic 6 months after switching to entecavir + tenofovir.Virologic response to entecavir + tenofovir combination therapy and tenofovir monotherapy appeared to be similar in most patients, but not with the entecavir + adefovir combination.

View details for DOI 10.1007/s10620-012-2402-2

View details for PubMedID 23010744
High Frequency of Recurrent Viremia After Hepatitis B e Antigen Seroconversion and Consolidation Therapy JOURNAL OF CLINICAL GASTROENTEROLOGY Chaung, K. T., Ha, N. B., Trinh, H. N., Garcia, R. T., Nguyen, H. A., Nguyen, K. K., Garcia, G., Ahmed, A., Keeffe, E. B., Nguyen, M. H. 2012; 46 (10): 865-870
Abstract

The primary treatment endpoint for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B is HBeAg seroconversion; however, data on the durability of response are inconsistent.Our goal was to investigate the rate of recurrent viremia after HBeAg seroconversion and subsequent discontinuation of therapy.We retrospectively studied 88 consecutive Asian American patients who achieved HBeAg seroconversion [loss of HBeAg and development of antibody to HBeAg (anti-HBe)] among 458 HBeAg-positive patients who received oral antiviral therapy at 3 US clinics between March 1998 and November 2010. Recurrent viremia was defined as reappearance of detectable serum hepatitis B virus DNA (>100 IU/mL) on 2 consecutive laboratory tests from previously undetectable levels.Antiviral medications used at the time of HBeAg seroconversion included: lamivudine (23%), adefovir (34%), entecavir (36%), tenofovir (4%), and combination therapy (3%). Antiviral therapy was continued after HBeAg seroconversion in 49 patients (group I) and discontinued in the other 39 patients after consolidation therapy [median=12 months (range, 1 to 55 mo)] (group II). No patients in group I experienced recurrent viremia, whereas 90% in group II did. Elevated alanine aminotransferase also occurred in 38% of group II patients [median peak alanine aminotransferase 249 IU/mL (range, 93 to 1070 IU/mL)].Despite consolidation therapy, almost all patients who discontinued therapy after achieving HBeAg seroconversion and complete viral suppression experienced recurrent viremia, and close to half also experienced biochemical flares. HBeAg seroconversion does not seem to be a durable treatment endpoint for many patients, and they should be monitored carefully for virologic relapse and biochemical flares if antiviral therapy is withdrawn.

View details for DOI 10.1097/MCG.0b013e31825ceed9

View details for Web of Science ID 000312953400018

View details for PubMedID 22941429
Higher rates of hepatitis B surface antigen (HBsAg) seroclearance in males and in hepatitis B e-antigen negative chronic hepatitis B (CHB) among treatment naive patients in a large multicenter US cohort study 63rd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) Nguyen, L. H., Sonu, I. S., Kin, K. C., Trinh, H. N., Li, J., Zhang, J. Q., Ahmed, A., Nguyen, M. H. WILEY-BLACKWELL. 2012: 352A–352A
View details for Web of Science ID 000310955601327
Disease Presentation and Treatment in Patients with Hepatocellular Carcinoma (HCC) Associated with Hepatitis B Virus (HBV/HCC) and Patients with Hepatitis C Virus Associated HCC (HCV/HCC) 63rd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) Wantuck, J. M., Ha, N. B., Yip, B., Lin, H., Lee, P., Ahmed, A., Nguyen, M. H. WILEY-BLACKWELL. 2012: 651A–651A
View details for Web of Science ID 000310955602326
Incidence and Risk Factors in the Development of Hepatocellular Carcinoma (HCC) in Non-Cirrhotic and Cirrhotic Patients with Chronic Hepatitis B (CHB): Results of a Multicenter US Cohort Study 63rd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) Sonu, I. S., Nguyen, L. H., Chen, C., Kin, K. C., Ha, N. B., Trinh, H. N., Ahmed, A., Li, J., Zhang, J. Q., Nguyen, M. H. WILEY-BLACKWELL. 2012: 478A–479A
View details for Web of Science ID 000310955601591
Risk factors for hepatocellular carcinoma in patients with chronic liver disease: a case-control study CANCER CAUSES & CONTROL Ha, N. B., Ha, N. B., Ahmed, A., Ayoub, W., Daugherty, T. J., Chang, E. T., Lutchman, G. A., Garcia, G., Cooper, A. D., Keeffe, E. B., Nguyen, M. H. 2012; 23 (3): 455-462
Abstract

The majority of data on risk factors (RFs) for hepatocellular carcinoma (HCC) comes from studies involving populations without underlying liver disease. It is important to evaluate RFs for HCC in patients with chronic liver disease since HCC rarely occurs in those without underlying liver disease. We conducted a hospital-based case-control study of 259 incident HCC cases and 781 controls by convenience sampling between 02/2001 and 12/2009 from the liver clinic at Stanford University Medical Center. The study population was 41% White, 14% Hispanic, 3% African American, 40% Asian American, and 2% other race/ethnicity. RFs were examined through medical records and an in-person questionnaire. Alcohol and tobacco use was calculated by cumulative grams of alcohol or cumulative pack(s) of cigarette consumed over one's lifetime. Diabetes mellitus (DM) was defined by random glucose level of ≥200 mg/dL. RFs were evaluated using multivariate logistic regression. Independent predictors of HCC risk, after mutual adjustment and additional control for alcohol use, etiology of liver diseases, and DM, included age >40 (OR = 8.5 [2.6-28.3]), male gender (OR = 3.5 [2.2-5.8]), presence of cirrhosis (OR = 2.8 [1.6-4.9]), Asian ethnicity (OR = 2.8 [1.8-4.6]), AFP > 50 (OR = 4.2 [2.6-6.8]), and cumulative lifetime tobacco use of >11,000 packs (OR = 1.7 [1.0-2.9]). Heavy prolonged cigarette smoking, but not alcohol use, was a significant independent predictor for HCC in patients with underlying liver disease. Besides older age, male gender, presence of cirrhosis, and elevated AFP, Asian ethnicity and heavy cumulative tobacco use are strong independent predictors of HCC.

View details for DOI 10.1007/s10552-012-9895-z

View details for Web of Science ID 000300891100006

View details for PubMedID 22258434
Outcomes after escalation of infliximab therapy in ambulatory patients with moderately active ulcerative colitis ALIMENTARY PHARMACOLOGY & THERAPEUTICS Rostholder, E., Ahmed, A., Cheifetz, A. S., Moss, A. C. 2012; 35 (5): 562-567
Abstract

Infliximab (IFX) therapy escalation during maintenance treatment occurs frequently in clinical practice in patients with ulcerative colitis (UC). Outcomes for these patients have not been described.To describe the prevalence of, and outcomes after, IFX escalation during maintenance therapy in patients with moderate-severe UC.Retrospective observational study of clinical outcomes in ambulatory patients with moderate-severe UC treated with maintenance IFX.Fifty-six ambulatory patients received IFX for moderate-severe UC; fifty (89%) responded and proceeded to maintenance therapy. Mean duration of maintenance therapy was 14 months, with mean follow-up of 38 months. Twenty-seven patients (54%) required IFX therapy escalation after a mean of six maintenance infusions. Clinical remission was noted in 36% of the entire cohort (18/50) at 12 months; 19% in the escalation group and 56% in the non-escalation group. Patients who required IFX escalation were less likely to be in clinical remission at 12 months (OR 0.2, 95% CI 0.1-0.6, P = 0.01) when compared with those who did not. During the follow-up period, 27% of patients required a colectomy, and the mean time to colectomy was 17 months. Patients in the escalation group required a colectomy in 33% of cases, compared with 21% of non-escalation patients.A significant proportion of ambulatory patients with UC treated with maintenance infliximab required therapy escalation over time. This was associated with lower remission, and higher colectomy, rates.

View details for DOI 10.1111/j.1365-2036.2011.04986.x

View details for Web of Science ID 000299832700007

View details for PubMedID 22239070
Prospective study of risk factors for hepatitis C virus acquisition by Caucasian, Hispanic, and Asian American patients JOURNAL OF VIRAL HEPATITIS Ho, E. Y., Ha, N. B., Ahmed, A., Ayoub, W., Daugherty, T., Garcia, G., Cooper, A., Keeffe, E. B., Nguyen, M. H. 2012; 19 (2): E105-E111
Abstract

Commonly known risk factors for infection with hepatitis C virus (HCV) include blood transfusion, injection drug use, intranasal cocaine use, and body tattoos. We hypothesized that Asian Americans infected with HCV may not identify with these established risk factors present in Caucasians and Hispanics, and our aim was to conduct a survey of risk factors in HCV-infected patients in these ethnic groups. In this prospective study, 494 patients infected with HCV completed a detailed risk assessment questionnaire at a liver centre in Northern California from 2001 to 2008. Among subjects participating in this study, 55% identified themselves as Caucasian, 20% as Hispanic, and 25% as Asian. Asian Americans were older, less likely to smoke or consume alcohol, and have a family history of cancer compared with Caucasians and Hispanics. The laboratory profiles were similar, and genotype 1 was the most common infection in all groups (74-75%). The great majority of Caucasians (94%) and Hispanics (86%) identified with commonly known risk factors, which was in contrast to 67% of Asians (P < 0.0001). The most common risk factors in Asians were blood transfusions (50%) and acupuncture (50%). Furthermore, 74% of Caucasians and 66% of Hispanics identified more than one major risk factor, while only 20% of Asians reported having more than one risk factor (P < 0.0001). Survey for established risk factors for acquisition of HCV may be more appropriate for risk assessment of Caucasians and Hispanics, but not for Asian Americans. These findings may guide the development of HCV screening in our increasingly diverse population.

View details for DOI 10.1111/j.1365-2893.2011.01513.x

View details for Web of Science ID 000299097400014

View details for PubMedID 22239506
Comparison of the Frequency of Coronary Artery Disease in Alcohol-Related Versus Non-Alcohol-Related Endstage Liver Disease AMERICAN JOURNAL OF CARDIOLOGY Patel, S., Kiefer, T. L., Ahmed, A., Ali, Z. A., Tremmel, J. A., Lee, D. P., Yeung, A. C., Fearon, W. F. 2011; 108 (11): 1552-1555
Abstract

There are conflicting data as to the prevalence of coronary artery disease (CAD) in patients with end-stage liver disease (ESLD) being assessed for liver transplantation (LT). The aims of this study were to compare the prevalence of CAD in patients with alcohol-related versus non-alcohol-related ESLD and to assess the diagnostic utility of dobutamine stress echocardiography (DSE) in predicting angiographically important CAD. Consecutive patients with ESLD being assessed for LT (n = 420, mean age 56 ± 8 years) were identified and divided into groups of those with alcohol-related ESLD (n = 125) and non-alcohol-related ESLD (n = 295). Demographic characteristics, CAD risk factors, results of DSE, and coronary angiographic characteristics were recorded. There were no significant differences in age or CAD risk factors between groups. The incidence of severe CAD (>70% diameter stenosis) was 2% in the alcohol-related ESLD group and 13% in the non-alcohol-related ESLD group (p <0.005). In the 2 groups, the presence of ≥1 CAD risk factor was associated with significant CAD (p <0.05 for all). Absence of cardiac risk factors was highly predictive in ruling out angiographically significant disease (negative predictive value 100% for alcohol-related ESLD and 97% for non-alcohol-related ESLD). DSE was performed in 205 patients. In the 2 groups, DSE had poor predictive value for diagnosing significant CAD but was useful in ruling out patients without significant disease (negative predictive value 89% for alcohol-related ESLD and 80% for non-alcohol-related ESLD). In conclusion, there was a significantly lower prevalence of severe CAD in patients with alcohol-related ESLD. These findings suggest that invasive coronary angiography may not be necessary in this subgroup, particularly in the absence of CAD risk factors and negative results on DSE.

View details for DOI 10.1016/j.amjcard.2011.07.013

View details for PubMedID 21890080
High Rate of Complete Viral Suppression With Combination Therapy in Patients With Chronic Hepatitis B and Prior Treatment Failure JOURNAL OF CLINICAL GASTROENTEROLOGY Wong, C. R., Trinh, H. N., Yip, B., Nguyen, H. A., Garcia, R. T., Ahmed, A., Keeffe, E. B., Nguyen, M. H. 2011; 45 (10): 900-905
Abstract

Combination therapy for chronic hepatitis B virus (HBV) infection is recommended for patients with antiviral resistance (AVR) or partial response (PR) to earlier antiviral therapy; however, data on outcomes are limited.To determine the rate of complete viral suppression (CVS) with combination therapy and to compare CVS among different indications and treatment regimens.A cohort of 109 consecutive patients with chronic hepatitis B from 3 liver clinics in Northern California was retrospectively studied. All patients started combination therapy between April 2004 and August 2009 for the following indications: AVR (n = 29), PR (n = 60), or others (n = 20). Combination treatments included lamivudine (LAM), adefovir (ADV), telbivudine (LdT), entecavir (ETV), tenofovir (TDF), and emtricitabine (FTC). CVS was defined as undetectable serum HBV DNA <100 IU/mL.Among the patients, who were nearly all Asian (99%), 73% had ≥ 2 prior treatments and 82% had treatment failure (AVR or PR). Median treatment duration of combination therapy was 21 months (range, 6 to 50 mo). The majority (77%) achieved CVS after 6 months of various combination regimens: 80% for ETV+TDF, 76% for TDF+LAM or FTC or LdT, 75% for ETV+ADV, and 69% for ADV+LAM or LdT (P = 0.86). After 6 months of therapy, CVS was observed in a similar proportion of patients treated for PR and AVR (72% and 74%, respectively).Although the majority of 109 treatment-experienced patients had prior treatment failure, high rates of CVS were rapidly achieved and did not significantly differ between indications of AVR and PR or between ETV-based and TDF-based regimens.

View details for DOI 10.1097/MCG.0b013e318224d64f

View details for PubMedID 21778896
HEPATITIS B VIRUS (HBV) REVERSE TRANSCRIPTASE MUTATION IS RARE IN TREATMENT-NAIVE PATIENTS WITH CHRONIC HEPATITIS B (CHB): A PROSPECTIVE MULTICENTER STUDY USING INNO-LIPA HBV DR3 ASSAY 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) Nguyen, M. H., Trinh, H. N., Garcia, R. T., Nguyen, H. A., Levitt, B. S., Cooper, A. D., Keeffe, E. B., Khanh Nguyen, K., Daugherty, T., Lutchman, G. A., Ayoub, W. S., Ahmed, A., Garcia, G., Da Silveira, E. B. WILEY-BLACKWELL. 2011: 1080A–1080A
View details for Web of Science ID 000295578003737
LOW INCIDENCE OF HEPATITIS B E ANTIGEN (HBEAG) SEROCONVERSION WITH ORAL MONOTHERAPY IN CHRONIC HEPATITIS B (CHB) TREATMENT-NAiVE PATIENTS AT YEAR 1 IN CLINICAL PRACTICE 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) Lin, B., Ha, N. B., Liu, A., Trinh, H. N., Nguyen, H. A., Nguyen, K., Garcia, R. T., Keeffe, E. B., Garcia, G., Ahmed, A., Nguyen, M. H. WILEY-BLACKWELL. 2011: 1045A–1046A
View details for Web of Science ID 000295578003664
Adefovir (ADV) Partial Response in Patients with Chronic Hepatitis B (CHB): Switch Versus Add-On Therapy 76th Annual Scientific Meeting of the American-College-of-Gastroenterology Yip, B., Huy Trinh, H., Khanh Nguyen, K., Huy Nguyen, H., Garcia, R., Keeffe, E., Ahmed, A., Mindie Nguyen, M. NATURE PUBLISHING GROUP. 2011: S108–S108
View details for Web of Science ID 000299772000275
Incidence and Predictors of Recurrent Hepatocellular Carcinoma (HCC) Following Partial Hepatectomy 76th Annual Scientific Meeting of the American-College-of-Gastroenterology Vergara, A. M., Gallo, A., Nghiem Ha, N., Bonham, C., Esquivel, C., Concepcion, W., Melcher, M., Daugherty, T., Ayoub, W., Lutchman, G., Ahmed, A., Mindie Nguyen, M. NATURE PUBLISHING GROUP. 2011: S103–S104
View details for Web of Science ID 000299772000262
HEPATOCELLULAR CARCINOMA (HCC) INCIDENCE IN US PATIENTS WITH VIRAL OR NON-VIRAL ETIOLOGY OF CIRRHOSIS 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) Mair, R. D., Valenzuela, A., Ha, N. B., Ahmed, A., Ayoub, W. S., Daugherty, T., Lutchman, G. A., Garcia, G., Cooper, A. D., Keeffe, E. B., Nguyen, M. H. WILEY-BLACKWELL. 2011: 1414A–1414A
View details for Web of Science ID 000295578004707
Ethnic Differences in Viral Dominance Patterns in Patients with Hepatitis B Virus and Hepatitis C Virus Dual Infection HEPATOLOGY Nguyen, L. H., Ko, S., Wong, S. S., Tran, P. S., Trinh, H. N., Garcia, R. T., Ahmed, A., Lutchman, G. A., Keeffe, E. B., Nguyen, M. H. 2011; 53 (6): 1839-1845
Abstract

Studies of hepatitis B virus (HBV)/hepatitis C virus (HCV) dual infection are limited. Most are small, conducted outside the United States, and compare dual infection with HCV monoinfection. The goal of this study was to characterize HBV/HCV dual infection in a large multiethnic, matched, case-control study of dual-infected and HBV-monoinfected patients at two United States centers. Using an International Classification of Disease Version 9 electronic query and chart review, we identified 115 HBV/HCV dual-infected patients with serial HBV DNA, HCV RNA, and alanine aminotransferase (ALT) levels. As a control, 115 HBV-monoinfected patients were chosen randomly and matched with cases by age ±10 years, sex, Asian versus non-Asian ethnicity, and study site. Both groups had similar sex, ethnic, and age distributions (68% male, 83% Asian, age 52 ± 14 years). The median follow-up times were 33 and 38 months for the dual-infected and monoinfected groups, respectively. More monoinfected patients received HBV antiviral therapy than dual-infected patients (43% versus 24%; P = 0.002). No significant difference was detected between the proportion of monoinfected versus dual-infected patients with ALT above 40 U/L at presentation or during follow-up. Dual infection patients exhibited very little HBV/HCV codominance at baseline and throughout follow-up: patients had either HBV viremia with low or absent HCV RNA or detectable HCV RNA with low or absent HBV DNA. Asian ethnicity was predictive of HBV dominance after adjusting for sex, age, and baseline ALT elevation (odds ratio 7.35; P = 0.01).HBV/HCV dual-infected and HBV-monoinfected patients had similar clinical characteristics. Asian ethnicity is a major independent predictor of HBV-dominant disease, and HCV dominance with undetectable HBV DNA is more common in non-Asian individuals. Larger studies are needed to further characterize the natural history of HBV/HCV dual infection in Asian and non-Asian individuals.

View details for DOI 10.1002/hep.24308

View details for Web of Science ID 000291307300009

View details for PubMedID 21425314
Enhanced efficacy of pegylated interferon alpha-2a over pegylated interferon and ribavirin in chronic hepatitis C genotype 4A randomized trial and quality of life analysis LIVER INTERNATIONAL Kamal, S. M., Ahmed, A., Mahmoud, S., Nabegh, L., El Gohary, I., Obadan, I., Hafez, T., Ghoraba, D., Aziz, A. A., Metaoei, M. 2011; 31 (3): 401-411
Abstract

The therapy of chronic hepatitis C genotype 4 (HCV-4) has not been optimized yet. This randomized, prospective, parallel-group clinical trial compared the efficacy and safety of pegylated interferon α-2a (PEG-IFN α-2a) plus ribavirin and PEG-IFN α-2b plus ribavirin and assessed the health-related quality of life (HRQOL) in patients with chronic HCV-4.Eligible patients with proven chronic HCV-4 were randomized to receive either a weekly dose of PEG-IFN α-2a (180 μg) or PEG-IFN α-2b (1.5 μg/kg) and a daily dose of ribavirin (1000-1200 mg) for 48 weeks with 24 weeks post-treatment follow-up. The primary end point was sustained virological response (SVR) defined by undetectable HCV RNA 24 weeks after treatment. The Short form-36 Health Survey version 2 (SF-36v2) and the Chronic Liver Disease questionnaires (CLDQ) were assessed before, during and after therapy.The overall SVR rate of the entire cohort was 59.9%. The SVR rates were significantly higher in patients treated with PEG-IFN α-2a and ribavirin (Group A; n=109) compared with those treated with PEG-IFN α-2b and ribavirin (Group B; n=108, 70.6 vs. 54.6%, respectively; P=0.017). The relapse rates were 5.1% for PEG-IFN α-2a and 15.7% for PEG-IFN α-2b (P=0.0019). The SF-36v2 and CLDQ were low during therapy and improved significantly after therapy successful therapy.Pegylated interferon α-2a plus ribavirin was significantly more effective than PEG-IFN α-2b and ribavirin therapy in the treatment of chronic HCV-4 patients. The tolerability and adverse events were comparable between the two regimens. The HRQOL improved significantly after successful PEG-IFN α-2a plus ribavirin therapy.

View details for DOI 10.1111/j.1478-3231.2010.02435.x

View details for Web of Science ID 000286836900018

View details for PubMedID 21281434
LOW PREVALENCE OF HEPATITIS B VIRUS REVERSE TRANSCRIPTASE MUTATIONS IN TREATMENT-NAiVE PATIENTS WITH CHRONIC HEPATITIS B USING INNO-LIPA HBV DR3 IN A MULTICENTER STUDY 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases Nguyen, M. H., Trinh, H. N., Garcia, R. T., Nguyen, H. A., Nguyen, K., Cooper, A. D., Levitt, B. S., Keeffe, E. B., Ayoub, W. S., Daugherty, T., Da Silveira, E. B., Ahmed, A. WILEY-BLACKWELL. 2010: 1001A–1001A
View details for Web of Science ID 000288775602036
RAPID COMPLETE VIRAL SUPPRESSION WITH COMBINATION THERAPY IN 109 TREATMENT-EXPERIENCED PATIENTS WITH CHRONIC HEPATITIS B 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases Wong, C. R., Trinh, H. N., Yip, B., Nguyen, H. A., Garcia, R. T., Ahmed, A., Keeffe, E. B., Nguyen, M. H. WILEY-BLACKWELL. 2010: 544A–544A
View details for Web of Science ID 000288775600455
RISK FACTORS FOR HEPATOCELLULAR CARCINOMA AMONG PATIENTS WITH UNDERLYING CHRONIC LIVER DISEASE: A PROSPECTIVE STUDY 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases Ha, N. B., Ha, N. B., Ahmed, A., Ayoub, W. S., Daugherty, T., Lutchman, G. A., Garcia, G., Cooper, A. D., Keeffe, E. B., Nguyen, M. H. WILEY-BLACKWELL. 2010: 682A–682A
View details for Web of Science ID 000288775601077
Diabetes Mellitus Increases the Risk of Mortality Following Liver Transplantation Independent of MELD Score DIGESTIVE DISEASES AND SCIENCES Samuelson, A. L., Lee, M., Kamal, A., Keeffe, E. B., Ahmed, A. 2010; 55 (7): 2089-2094
Abstract

Patients with diabetes mellitus overall experience worse health outcomes than non-diabetics, but whether this is true among recipients of liver transplantation still remains unclear. The aim of this study was to compare the mortality of diabetic and non-diabetic patients following liver transplantation.We conducted a retrospective analysis of 530 adult patients undergoing liver transplantation at Stanford University Medical Center from February 1995 to July 2006. Information on diabetes mellitus was available for 431 patients; 96 patients who had acute liver failure (n = 17), combined liver and kidney transplantation (n = 28), or died prior to discharge (n = 51) were excluded from analysis.Over a mean follow-up of 4.5 years, survival was 81% in the diabetic group and 94% among controls (p = <0.0001). After controlling for age (mean +/- SD: 54.4 +/- 7.6 in diabetics, 50.1 +/- 9.6 in controls), body mass index (28.6 +/- 6.6 in diabetics, 27.1 +/- 5.4 in controls), presence of hepatitis C, and MELD score (17 +/- 9.6 in diabetics, 19 +/- 10.2 in controls), diabetes mellitus remained a significant predictor of death (HR 3.11, p = 0.01).Diabetes mellitus is an independent risk factor for mortality following liver transplantation. Further investigation of this relationship should focus on the impact of more intensive pre- and post-liver transplantation glucose control, cardiovascular risk factor reduction, and the effects of accelerated atherosclerosis in the setting of immune suppression.

View details for DOI 10.1007/s10620-010-1267-5

View details for Web of Science ID 000278900200039

View details for PubMedID 20467898
Pseudomyxoma Peritonei Masquerading As Ascites Secondary to Alcoholic Cirrhosis DIGESTIVE DISEASES AND SCIENCES Nguyen, T., Ahmed, A. 2009; 54 (10): 2053-2055
View details for DOI 10.1007/s10620-009-0881-6

View details for PubMedID 19575292
Transarterial Chemoinfusion for Hepatocellular Carcinoma as Downstaging Therapy and a Bridge toward Liver Transplantation AMERICAN JOURNAL OF TRANSPLANTATION De Luna, W., Sze, D. Y., Ahmed, A., Ha, B. Y., Ayoub, W., Keeffe, E. B., Cooper, A., Esquivel, C., Nguyen, M. H. 2009; 9 (5): 1158-1168
Abstract

Favorable outcomes after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) are well described for patients who fall within defined tumor criteria. The effectiveness of tumor therapies to maintain tumor characteristics within these criteria or to downstage more advanced tumors to fall within these criteria is not well understood. The aim of this study was to examine the response to transcatheter arterial chemoinfusion (TACI) in HCC patients awaiting LT and its efficacy for downstaging or bridging to transplantation. We performed a retrospective study of 248 consecutive TACI cases in 122 HCC patients at a single U.S. medical center. Patients were divided into two groups: those who met the Milan criteria on initial HCC diagnosis (n = 95) and those with more advanced disease (n = 27). With TACI treatment, 87% of the Milan criteria group remained within the Milan criteria and 63% of patients with more advanced disease were successfully downstaged to fall within the Milan criteria. In conclusion, TACI appears to be an effective treatment as a bridge to LT for nearly 90% patients presenting within the Milan criteria and an effective downstaging modality for over half of those whose tumor burden was initially beyond the Milan criteria.

View details for DOI 10.1111/j.1600-6143.2009.02576.x

View details for Web of Science ID 000265222200023

View details for PubMedID 19344435
Ultra-Deep Pyrosequencing of Hepatitis B Virus Quasispecies from Nucleoside and Nucleotide Reverse-Transcriptase Inhibitor (NRTI)-Treated Patients and NRTI-Naive Patients 15th Conference on Retroviruses and Opportunistic Infections Margeridon-Thermet, S., Shulman, N. S., Ahmed, A., Shahriar, R., Liu, T., Wang, C., Holmes, S. P., Babrzadeh, F., Gharizadeh, B., Hanczaruk, B., Simen, B. B., Egholm, M., Shafer, R. W. OXFORD UNIV PRESS INC. 2009: 1275–85
Abstract

The dynamics of emerging nucleoside and nucleotide reverse-transcriptase inhibitor (NRTI) resistance in hepatitis B virus (HBV) are not well understood because standard dideoxynucleotide direct polymerase chain reaction (PCR) sequencing assays detect drug-resistance mutations only after they have become dominant. To obtain insight into NRTI resistance, we used a new sequencing technology to characterize the spectrum of low-prevalence NRTI-resistance mutations in HBV obtained from 20 plasma samples from 11 NRTI-treated patients and 17 plasma samples from 17 NRTI-naive patients, by using standard direct PCR sequencing and ultra-deep pyrosequencing (UDPS). UDPS detected drug-resistance mutations that were not detected by PCR in 10 samples from 5 NRTI-treated patients, including the lamivudine-resistance mutation V173L (in 5 samples), the entecavir-resistance mutations T184S (in 2 samples) and S202G (in 1 sample), the adefovir-resistance mutation N236T (in 1 sample), and the lamivudine and adefovir-resistance mutations V173L, L180M, A181T, and M204V (in 1 sample). G-to-A hypermutation mediated by the apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like family of cytidine deaminases was estimated to be present in 0.6% of reverse-transcriptase genes. Genotype A coinfection was detected by UDPS in each of 3 patients in whom genotype G virus was detected by direct PCR sequencing. UDPS detected low-prevalence HBV variants with NRTI-resistance mutations, G-to-A hypermutation, and low-level dual genotype infection with a sensitivity not previously possible.

View details for DOI 10.1086/597808

View details for Web of Science ID 000265035500007

View details for PubMedID 19301976

View details for PubMedCentralID PMC3353721
The Asymptomatic Outpatient with Abnormal Liver Function Tests CLINICS IN LIVER DISEASE Krier, M., Ahmed, A. 2009; 13 (2): 167-?
Abstract

Traditionally, the constellation of biochemistry tests including liver enzymes, total bilirubin, and hepatic synthetic measures (prothrombin time (PT) and serum albumin level) are referred to as liver function tests (LFTs). Abnormal LFTs can be encountered during primary health care visits, routine blood donation, and insurance screening. A reported 1% to 4% of asymptomatic patients exhibit abnormal LFTs, leading to a sizeable number of annual consultations to a gastroenterology and/or hepatology practice. A cost-effective and systematic approach is essential to the interpretation of abnormal LFTs. A review of pattern of abnormal LFTs, detailed medical history, and a comprehensive physical examination help establish a foundation for further individualized testing. Further investigation often involves biochemical testing for disease-specific markers, radiographic imaging, and even consideration of a liver biopsy. In the following account, markers of hepatic injury are reviewed followed by a discussion on an approach to various patterns of abnormal LFTs in an asymptomatic patient.

View details for DOI 10.1016/j.cld.2009.02.001

View details for Web of Science ID 000267207200002

View details for PubMedID 19442912
Adenovirus-Induced Acute Liver Failure DIGESTIVE DISEASES AND SCIENCES Rothenberg, M., Cheung, R., Ahmed, A. 2009; 54 (2): 218-221
View details for DOI 10.1007/s10620-008-0628-9

View details for Web of Science ID 000262968200006

View details for PubMedID 19034647
Management of Biliary Strictures Following Liver Transplantation DIGESTIVE DISEASES AND SCIENCES Alexopoulos, S. P., Henningsen, J. A., Jeffrey, R. B., Bonham, C. A., Ahmed, A., Gonzalez, S. A. 2009; 54 (1): 25-27
View details for DOI 10.1007/s10620-008-0626-y

View details for Web of Science ID 000261653400007

View details for PubMedID 19034649
Prevalence of Colorectal Neoplasms in Asian Americans DIGESTIVE DISEASES AND SCIENCES Lam, K. D., Garcia, R. T., Nguyen, L. H., Trinh, H., Triadafilopoulos, G., Phan, J. T., Nguyen, K., Nguyen, H., Ahmed, A., Nguyen, M. H. 2009; 54 (1): 160-167
Abstract

To determine the yield of colonoscopy in a predominantly Asian American gastroenterology practice in California from 8/2003 to 2/2005.A total 2,723 subjects were included: 87% were Asian and 13% were non-Asian. Advanced neoplasia prevalence was 12% in Asian men and 9% in non-Asian men (P = 0.21), and 8% and 7% in women (P = 0.62). Similar results were found in asymptomatic patients (13% and 13%, P = 0.99, for men; 8% and 6%, P = 0.46, for women). Factors associated with presence of advanced neoplasia were total number of polyps and presence of right-sided lesions. Asian men were more likely to have neoplasia overall compared with non-Asian men with odds ratio (OR) of 2.14 (1.23-3.72); however, there were no significant differences in the prevalences of advanced neoplasia in the two groups.Colorectal neoplasia is as prevalent in Asian Americans and preventive guidelines for colorectal cancer should also be advocated for this ethnic group.

View details for DOI 10.1007/s10620-008-0499-0

View details for PubMedID 18975084
Bidirectionally Adjustable TIPS Reduction by Parallel Stent and Stent-Graft Deployment JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Sze, D. Y., Hwang, G. L., Kao, J. S., Frisoli, J. K., Kee, S. T., Razavi, M. K., Ahmed, A. 2008; 19 (11): 1653-1658
Abstract

Excessive shunting through transjugular intrahepatic portosystemic shunts (TIPS) can cause life-threatening hepatic encephalopathy and insufficiency. Intentional reduction of flow may be effective but difficult to control. The present report describes refinements of the parallel stent/stent-graft technique of flow reduction that is adjustable in either direction. Six patients underwent TIPS reduction with varying stent positioning and a variety of commercial products. Flow was adjusted by iterative balloon dilatation of the stent and stent-graft, resulting in a mean gradient increase of 8 mm Hg. All cases were technically successful, but 1-year survival was seen in only the patient who underwent liver transplantation.

View details for DOI 10.1016/j.jvir.2008.08.011

View details for Web of Science ID 000260694700018

View details for PubMedID 18823797
Treatment, outcomes of transcatheter arterial chemoinfusion (TACI) in patients with unresectable hepatocellular carcinoma (HCC) prior to orthotropic liver transplantation. 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases de Luna, W., Ha, B. Y., Ahmed, A., Sze, D., Keeffe, E. B., Nguyen, M. H. WILEY-BLACKWELL. 2007: 517A–518A
View details for Web of Science ID 000249910400634
Long term outcomes of liver transplantation in a high-MELD cohort 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases Lee, J., Lee, M., Shapiro, L., Yang, A. L., Lapasaran, A. S., Parvez, S., Komal, A., Keeffe, E. B., Esquivel, C. O., Ahmed, A. WILEY-BLACKWELL. 2007: 506A–507A
View details for Web of Science ID 000249910400609
Long-term survival of patients with unresectable hepatocellular carcinoma treated with transcatheter arterial chemoinfusion ALIMENTARY PHARMACOLOGY & THERAPEUTICS Ha, B. Y., Ahmed, A., Sze, D. Y., Razavi, M. K., Simpson, N., Keeffe, E. B., Nguyen, M. H. 2007; 26 (6): 839-846
Abstract

Transcatheter arterial chemoembolization (TACE) has become one of the most common treatments for unresectable hepatocellular carcinoma. Published studies of TACE report a 5-16% risk of serious complications. Compared with TACE, transcatheter arterial chemoinfusion (TACI) may have similar efficacy and fewer side effects.To examine the clinical outcomes of TACI.We performed a retrospective cohort study of 345 consecutive TACI cases in 165 patients performed at a single United States medical center between 1998 and 2002. Primary outcomes were tumour response and survival rates.Only seven patients were hospitalized for more than 24 h after the procedure, and only three patients had worsening of liver function within 30 days of TACI. Survival was significantly poorer for patients with tumour-node-metastasis (TNM) IV compared to those with TNM I-III and also for patients with Child's class B/C vs. A. Following adjustment for age, gender, ethnicity and aetiology of liver diseases, independent predictors of poor survival were Child's class B/C [Hazard Ratio (HR) = 1.69, P = 0.024] and TNM IV staging (HR = 1.63, P = 0.014).TACI appears to be safe and effective for unresectable hepatocellular carcinoma with TNM stage I-III; randomized controlled trials are needed to compare TACI to TACE.

View details for DOI 10.1111/j.1365-2036.2007.03424.x

View details for Web of Science ID 000249130100008

View details for PubMedID 17767468
Sustained virological response to interferon-based antiviral therapy by viral genotype in recurrent hepatitis C patients following liver transplantation 72nd Annual Meeting of the American-College-of-Gastroenterology Waechter, A., Williams, J., Lee, J., Shapiro, L., Lee, M., Kamal, A., Keeffe, E. B., Ahmed, A. NATURE PUBLISHING GROUP. 2007: S240–S241
View details for Web of Science ID 000249397800341
Treatment outcomes of transcatheter arterial chemoinfusion (TACI) in patients with unresectable hepatocellular carcinoma (HCC) prior to orthotropic liver transplantation 72nd Annual Meeting of the American-College-of-Gastroenterology de Lunq, W., Choi, B. Y., Ahmed, A., Sze, D., Keefe, E. B., Nguyen, M. H. NATURE PUBLISHING GROUP. 2007: S239–S239
View details for Web of Science ID 000249397800337
The pre-operative utility of dobutamine stress echocardiography in patients undergoing liver transplantation 72nd Annual Meeting of the American-College-of-Gastroenterology Shapiro, L., Lee, M., Lee, J., Lapasaran, A. S., Fearon, W., Kamal, A., Ahmed, A. NATURE PUBLISHING GROUP. 2007: S437–S437
View details for Web of Science ID 000249397800865
Current indications and contraindications for liver transplantation. Clinics in liver disease Ahmed, A., Keeffe, E. B. 2007; 11 (2): 227-247
Abstract

Survival rates after liver transplantation have improved steadily because of earlier referral and timely evaluation, judicious patient selection, improved surgical techniques, superior immunosuppressive regimens, and effective prevention of perioperative opportunistic infections. Indications and contraindications for liver transplantation are undergoing constant modifications with the goal of improving survival and functional status of patients who have end-stage liver disease or acute liver failure. Potential candidates for liver transplantation should meet minimal listing criteria and not have contraindications to liver transplantation. Currently, the Model for End-stage Liver Disease score is used for organ allocation, but it may have future application in patient-selection criteria.

View details for PubMedID 17606204
Dermatologic disorders associated with chronic hepatitis C: Effect of interferon therapy CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Berk, D. R., Bayliss Mallory, S., Keeffe, E. B., Ahmed, A. 2007; 5 (2): 142-151
Abstract

Chronic hepatitis C virus infection (HCV) is associated with extrahepatic manifestations, including such dermatologic conditions as mixed cryoglobulinemia, porphyria cutanea tarda, and lichen planus. Patients with chronic HCV and extrahepatic manifestations are often excluded from clinical trials evaluating interferon (IFN) therapy due to concerns about poor response, adverse events, and toxicity. Thus, data regarding the efficacy of IFN not only on the underlying chronic HCV, but also on extrahepatic manifestations, are limited in these patients. Case reports suggest that the response of dermatologic extrahepatic manifestations to IFN in patients with chronic HCV is highly variable. This review summarizes available data on dermatologic conditions associated with chronic HCV and their response to IFN therapy.

View details for DOI 10.1016/j.cgh.2006.06.010

View details for Web of Science ID 000244511700004

View details for PubMedID 16919505
Global transcriptional response to interferon is a determinant of HCV treatment outcome and is modified by race HEPATOLOGY He, X., Ji, X., Hale, M. B., Cheung, R., Ahmed, A., Guo, Y., Nolan, G. P., Pfeffer, L. M., Wright, T. L., Risch, N., Tibshirani, R., Greenberg, H. B. 2006; 44 (2): 352-359
Abstract

Interferon (IFN)-alpha-based therapy for chronic hepatitis C is effective in fewer than 50% of all treated patients, with a substantially lower response rate in black patients. The goal of this study was to investigate the underlying host transcriptional response associated with interferon treatment outcomes. We collected peripheral blood mononuclear cells from chronic hepatitis C patients before initiation of IFN-alpha therapy and incubated the cells with or without IFN-alpha for 6 hours, followed by microarray assay to identify IFN-induced gene transcription. The microarray datasets were analyzed statistically according to the patients' race and virological responses to subsequent IFN-alpha treatment. The global induction of IFN-stimulated genes (ISGs) was significantly greater in sustained virological responders compared with nonresponders and in white patients compared with black patients. In addition, a significantly greater global induction of ISGs was observed in sustained virological responders compared with nonresponders within the group of white patients. The level of IFN-induced signal transducer and activator of transcription (STAT) 1 activation, a key component of the Janus kinase (JAK)-STAT signaling pathway, correlated with the global induction of ISGs and was significantly higher in white patients than in black patients. In conclusion, both treatment outcome and race are associated with different transcriptional responses to IFN-alpha. Because this difference is evident in the global induction of ISGs rather than a selective effect on a subset of such genes, key factors affecting the outcome of IFN-alpha therapy are likely to act at the JAK-STAT pathway that controls transcription of downstream ISGs.

View details for DOI 10.1002/hep.21267

View details for PubMedID 16871572
Progressive asymptomatic occlusion of a TIPS in a patient with Budd-Chiari syndrome JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Sze, D. Y., Frisoli, J. K., Macksood, D. J., Dovichi, E. A., Ahmed, A., Keeffe, E. B. 2006; 17 (4): 737-739
View details for DOI 10.1097/01.RVI.0000208620.56190.3C

View details for Web of Science ID 000236836700021

View details for PubMedID 16614160
Portal, spienic, and superior mesenteric vein thrombosis in a patient with latent essential thrombocythemia and hyperhomocysteinemia JOURNAL OF CLINICAL GASTROENTEROLOGY Berk, D. R., Ahmed, A. 2006; 40 (3): 227-228
View details for Web of Science ID 000236816600012

View details for PubMedID 16633126
Significant histologic disease in HBV-infected patients with normal to minimally elevated ALT levels at initial evaluation 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases Nguyen, M. H., Trinh, H., Garcia, R. T., Ahmed, A., Keeffe, E. B. WILEY-BLACKWELL. 2005: 593A–593A
View details for Web of Science ID 000232480302066
A pharmacoeconomic analysis of the registration trials: Peginterferon alfa-2a plus ribvarin versus peginterferon alfa-2b plus ribavarin for treatment of genotype 1 chronic hepatitis C 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases Kamal, A., Lim, J. K., Crockett, S., Ahmed, A. WILEY-BLACKWELL. 2005: 352A–352A
View details for Web of Science ID 000232480300391
Diminutive colon polyps in Asians are more likely to be adenomatous compared to non-Asians 70th Annual Meeting of the American-College-of-Gastroenterology Lam, K. D., Nguyen, M. H., Trinh, H. N., Nguyen, L. H., Nguyen, K. K., Nguyen, H. A., Ahmed, A., Garcia, R. T. NATURE PUBLISHING GROUP. 2005: S391–S392
View details for Web of Science ID 000231853502335
Prophylactic TIPS for large gastric varices: A pilot study with four-year prospective experience 70th Annual Meeting of the American-College-of-Gastroenterology Kamal, A., Crockett, S., Yeh, R. W., Roost, J., Keeffe, E. B., Ahmed, A. NATURE PUBLISHING GROUP. 2005: S110–S110
View details for Web of Science ID 000231853500265
Treatment outcomes of transcatheter arterial chemoinfusion (TACI) in patients with unresectable hepatocellular carcinoma (HCC) 69th Annual Meeting of the American-College-of-Gastroenterology Choi, B. Y., Ahmed, A., Razavi, M., Sze, D., Simpson, N., Garcia, R. T., Keeffe, E. B., Nguyen, M. H. NATURE PUBLISHING GROUP. 2004: S83–S83
View details for Web of Science ID 000224479700251
Endoscopic approach to the treatment of gastrointestinal bleeding. Techniques in vascular and interventional radiology Lim, J. K., Ahmed, A. 2004; 7 (3): 123-129
Abstract

Gastrointestinal endoscopy is the primary diagnostic and therapeutic modality in the management of gastrointestinal bleeding. Esophagogastroduodenoscopy, small bowel enteroscopy, and colonoscopy are well-established standards for initial evaluation of gastrointestinal bleeding, and have been used effectively for diagnosis, prognosis, and therapy. Although thermal, injection, and mechanical methods have been the mainstay of endoscopic therapy, promising new technologies such as endoscopic ultrasound and wireless capsule endoscopy will further advance our ability to improve morbidity and mortality from severe gastrointestinal hemorrhage. Herein we review current standards and recent advances in the endoscopic management of upper, lower, and obscure gastrointestinal bleeding.

View details for PubMedID 16015556
Older age and liver transplantation: A review LIVER TRANSPLANTATION Keswani, R. N., Ahmed, A., Keeffe, E. B. 2004; 10 (8): 957-967
Abstract

Patients older than 60 are undergoing transplantation with increasing frequency. Reports from several transplant centers document that overall short-term patient survival rates in seniors undergoing liver transplantation are comparable to survival rates of younger adults. However, specific subgroups of older patients may not fare as well. Seniors with far-advanced end-stage liver disease are high-risk for liver transplantation and have poor survival rates. In addition, seniors older than 65 have worse outcomes than those who are 60 to 65, and studies have shown increased mortality with increasing age as a continuous variable. On the other hand, the majority of seniors who survive liver transplantation have full or only minimally limited functional status. Preoperative evaluation of older patients for transplantation requires careful screening to exclude cardiopulmonary disease, malignancy, and other diseases of the aged. Paradoxically, seniors may benefit from a senescent immune system, which results in decreased requirements for immunosuppressive drugs, and possibly a lower rate of acute allograft rejection. Despite good overall short-term survival in the elderly, long-term survival may be worse because of an increased rate of long-term complications, such as malignancy and heart disease. In conclusion, although advanced age is a negative risk factor, advanced age alone should not exclude a patient from liver transplantation; however, it mandates thorough pretransplant evaluation and careful long-term follow-up with attention to usual health maintenance issues in the elderly.

View details for DOI 10.1002/lt.20155

View details for Web of Science ID 000223274300002

View details for PubMedID 15390320
Chronic hepatitis C with normal aminotransferase levels GASTROENTEROLOGY Ahmed, A., Keeffe, E. B. 2004; 126 (5): 1409-1415
View details for DOI 10.1053/j.gastro.2004.02.073

View details for Web of Science ID 000221217100022

View details for PubMedID 15131801
Hypoglycemic coma in a pregnant woman in association with hepatitis B virus carrier state and hepatocellular carcinoma JOURNAL OF CLINICAL GASTROENTEROLOGY Ahmed, A., Keeffe, E. B. 2004; 38 (2): 135-136
View details for Web of Science ID 000188547200012

View details for PubMedID 14745290
Factors involved in the development of chronic arsenic poisoning in Bangladesh ARCHIVES OF ENVIRONMENTAL HEALTH Sinha, S. K., Misbahuddin, M., Ahmed, A. N. 2003; 58 (11): 699-700
View details for Web of Science ID 000226315800004

View details for PubMedID 15702894
Living donor liver transplantation in a patient with hepatic epithelioid hemangioendothelioma JOURNAL OF CLINICAL GASTROENTEROLOGY Simpson, N. D., Ahmed, A. M., Simpson, P. W., Parkar, J. A., Keeffe, E. B., Ahmed, A. 2003; 37 (4): 349-350
View details for Web of Science ID 000185458400017

View details for PubMedID 14506396
Prophylaxis against chemotherapy-induced reactivation of hepatitis B virus infection with lamivudine JOURNAL OF CLINICAL GASTROENTEROLOGY Simpson, N. D., Simpson, P. W., Ahmed, A. M., Nguyen, M. H., Garcia, G., Keeffe, E. B., Ahmed, A. 2003; 37 (1): 68-71
Abstract

The results of lamivudine therapy in 4 patients with chemotherapy-induced hepatitis B virus (HBV) reactivation are reported. Cancer chemotherapy-induced reactivation is a known complication in patients with chronic HBV infection or history of HBV infection with recovery. Reactivation of HBV infection has a broad spectrum of manifestations ranging from mild elevation of aminotransferase levels to fatal fulminant hepatitis. Lamivudine is a nucleoside analogue and a potent inhibitor of HBV reverse transcription. The 4 patients treated with lamivudine included 1 woman with breast cancer and 3 men with non-Hodgkin lymphoma, ranging from 41 to 63 years of age. All 4 patients were undergoing standard, multi-agent chemotherapy when they presented with HBV reactivation manifested by sudden onset of fatigue, jaundice, and HBV serology consistent with active HBV infection (detectable serum HBV DNA) in the absence of other known causes of acute hepatitis. Lamivudine therapy (100 mg/d in 3 patients and 150 mg/d in 1 patient) was initiated from 1 to 18 days following the diagnosis of HBV reactivation. All 4 patients showed rapid decrease in aminotransferase levels within 2 weeks after initiating lamivudine therapy. Unfortunately, hepatic synthetic function failed to improve in 2 patients, who both died. The remaining 2 patients had suppression of HBV DNA to undetectable levels after 1 and 4 months of treatment and had biochemical and clinical improvement. The 2 patients who died received lamivudine therapy for 8 days and for 3 weeks. There have been no randomized clinical trials to study the role of lamivudine for prophylaxis or treatment of HBV reactivation associated with chemotherapy. However, based on our limited experience, lamivudine may be efficacious in suppressing potentially fatal HBV reactivation secondary to chemotherapy in patients with chronic HBV infection or prior infection with recovery. Patients who undergo chemotherapy should be screened for the presence of markers of chronic hepatitis B infection or previous HBV infection. We recommend that patients with chronic HBV infection (positive HBV DNA and/or positive HBsAg) or history of HBV infection with recovery (positive hepatitis B core antibody with or without HBsAb) be considered for prophylactic lamivudine use to prevent chemotherapy-induced HBV reactivation.

View details for Web of Science ID 000183597500016

View details for PubMedID 12811213
Update on chronic hepatitis C. Comprehensive therapy Ahmed, A., Keeffe, E. B. 2003; 29 (4): 224-232
Abstract

Strategies for the diagnosis and treatment of chronic hepatitis C continue to evolve. Liver biopsy is now used selectively rather than routinely, and the combination peginterferon plus ribavirin is the treatment of choice for the majority of patients.

View details for PubMedID 14989044
The epidemiology of hepatitis C virus infection JOURNAL OF CLINICAL GASTROENTEROLOGY Yen, T., Keeffe, E. B., Ahmed, A. 2003; 36 (1): 47-53
Abstract

The prevalence of hepatitis C virus (HCV) infection varies in different populations, ranging from as low as 0.6% in volunteer blood donors to as high as 80% in injection drug users. The prevalence of HCV in a population can be predicted by risk factors associated with the transmission of infection. These risk factors include injection drug use, blood product transfusion, organ transplantation, hemodialysis, occupational injury, sexual transmission, and vertical transmission. We review the literature regarding the incidence and prevalence of HCV infection and the evidence supporting various modes of HCV transmission.

View details for Web of Science ID 000180031600015

View details for PubMedID 12488709
The role of recombinant human erythropoietin (epoetin alfa) in the management of ribavirin (RBV)-induced anemia Ahmed, A., Nguyen, M., Keswani, R. N., Grossi, J., Keeffe, E. B. NATURE PUBLISHING GROUP. 2002: S104–S104
View details for Web of Science ID 000178230400316
Hepatitis C virus and liver transplantation. Clinics in liver disease Ahmed, A., Keeffe, E. B. 2001; 5 (4): 1073-1090
Abstract

Advances in immunosuppressive therapy, operative techniques, and perioperative management have resulted in long-term patient survival rates approaching 90% following liver transplantation for chronic viral hepatitis. The increasing number of referrals for liver transplantation reflects the impact of chronic HCV infection as a cause of end-stage liver disease. Unlike hepatitis B, there is still no effective treatment in preventing recurrent hepatitis C after liver transplantation. The spectrum of allograft injury related to universal HCV infection recurrence ranges from no evidence of histologic injury to mild inflammation to severe disease with allograft failure in small proportion of patients. Various factors may explain these differing outcomes, including degree of pretransplantation viremia, HLA compatibility, presence of more pathogenic HCV genotypes, integrity of cellular immune response, and type of immunosuppression. Fortunately, patient survival does not seem to be affected short-term; the long-term outcome of liver transplantation for chronic hepatitis C is unclear but is likely to be decreased. Combination therapy with interferon plus ribavirin seems to be a promising treatment strategy for posttransplantation recurrent hepatitis C, and the use of pegylated interferon plus ribavirin may improve these results. Patients with moderate to severe allograft hepatitis are appropriate candidates for combination antiviral therapy. Histopathologically documented recurrent hepatitis C in liver transplant recipients is associated with impaired quality of life, inferior physical condition, and a higher incidence of depression compared with patients who did not have HCV and in those without HCV recurrence. In conclusion, it is possible that the continued improvements in antiviral therapy against HCV infection may ultimately decrease the number of patients needing liver transplantation. Suitable candidates with chronic HCV infection thus warrant treatment with pegylated interferon plus ribavirin combination therapy in the hope of decreasing disease progression. Recent studies, which require confirmation, suggest that nonresponders to standard antiviral therapy may benefit from maintenance therapy. The donor pool for patients with chronic hepatitis C and decompensated cirrhosis can be improved by using HCV-positive donors and by increasing utilization of newer surgical techniques, including adult-to-adult living-donor liver transplantation and split-liver transplantation.

View details for PubMedID 11685796
Liver transplantation: Evolving patient selection criteria CANADIAN JOURNAL OF GASTROENTEROLOGY Yu, A. S., Ahmed, A., Keeffe, E. B. 2001; 15 (11): 729-738
Abstract

The widespread recognition of the success of liver transplantation as a treatment for most types of acute and chronic liver failure has led to increased referrals for transplantation in the setting of a relatively fixed supply of cadaver donor organs. These events have led to a marked lengthening of the waiting time for liver transplantation, resulting in increased deaths of those on the waiting list and sicker patients undergoing transplantation. Nearly 5000 liver transplantations were performed in the United States in 2000, while the waiting list grew to over 17,000 patients. The mounting disparity between the number of liver transplant candidates and the limited supply of donor organs has led to reassessment of the selection and listing criteria for liver transplantation, as well as revision of organ allocation and distribution policies for cadaver livers. The development of minimal listing criteria for patients with chronic liver disease based on a specific definition for decompensation of cirrhosis has facilitated the more uniform listing of patients at individual centres across the United States. The United Network for Organ Sharing, under pressure from transplant professionals, patient advocacy groups and the federal government, has continuously revised allocation and distribution policies based on the ethical principles of justice for the individual patient versus optimal utility of the limited organ supply available annually. Beginning in 2002, it is likely that the Model for End-stage Liver Disease (MELD) score will be implemented to determine disease severity and direct donor organs to the sickest patients rather than to those with the longest waiting times.

View details for Web of Science ID 000172393600003

View details for PubMedID 11727003
Delayed fatal hemorrhage from pseudoaneurysm of the hepatic artery after percutaneous liver biopsy AMERICAN JOURNAL OF GASTROENTEROLOGY Ahmed, A., Samuels, S. L., Keeffe, E. B., Cheung, R. C. 2001; 96 (1): 233-237
Abstract

Hemorrhage is the most common serious complication of percutaneous liver biopsy. Liver biopsy is usually done in an outpatient setting because most significant hemorrhage is evident within a few hours after biopsy. Delayed hemorrhage occurs much less frequently but carries a much higher mortality. We present a 41-yr-old man with chronic hepatitis C who underwent a percutaneous liver biopsy uneventfully but was found to have a pseudoaneurysm of the hepatic artery 5 days later. Shortly after admission, the patient experienced bleeding into the liver from the pseudoaneurysm, which was controlled initially by angiographic embolization. However, recurrent bleeding could not be controlled by repeat angiography and surgical intervention, and the patient expired. The diagnosis and management of pseudoaneurysm of the hepatic artery complicating liver biopsy is reviewed.

View details for Web of Science ID 000166435400039

View details for PubMedID 11197259
A novel endoscopic appearance of idiopathic eosinophilic esophagitis ENDOSCOPY Ahmed, A., Matsui, S., Soetikno, R. 2000; 32 (6): S33-S33
View details for Web of Science ID 000087298000021

View details for PubMedID 10863926
The differential diagnosis of eosinophilic esophagitis JOURNAL OF CLINICAL GASTROENTEROLOGY Ahmad, M., Soetikno, R. M., Ahmed, A. 2000; 30 (3): 242-244
Abstract

Eosinophilic esophagitis is a morphologic finding that may result from a wide spectrum of clinical conditions. The distinctive histological features accompanying eosinophilic esophagitis may facilitate the diagnosis of the underlying disease entity. Unfortunately, there are no pathognomonic histologic characteristics associated with eosinophilic esophagitis. Clinical signs and symptoms, immunological markers, endoscopic findings, and response to therapy may help establish or confirm the diagnosis of a clinical condition that results in eosinophilic esophagitis. The following discussion outlines the causes of eosinophilia in an esophageal biopsy sample.

View details for Web of Science ID 000086336500006

View details for PubMedID 10777180
Management of gallstones and their complications AMERICAN FAMILY PHYSICIAN Ahmed, A., Cheung, R. C., Keeffe, E. B. 2000; 61 (6): 1673-1680
Abstract

The accurate differentiation of gallstone-induced biliary colic from other abdominal disease processes is the most crucial step in the successful management of gallstone disease. Despite the availability of many imaging techniques to demonstrate the presence of gallstones, clinical judgment ultimately determines the association of symptoms with cholelithiasis and its complications. Adult patients with silent or incidental gallstones should be observed and managed expectantly, with few exceptions. In symptomatic patients, the intervention varies with the type of gallstone-induced complication. In this article, we review the salient clinical features, diagnostic tests and therapeutic options employed in the management of gallstones and their complications.

View details for Web of Science ID 000086196400009

View details for PubMedID 10750875
Differential diagnosis of gallstone-induced complications SOUTHERN MEDICAL JOURNAL Ahmad, M., Cheung, R. C., Keeffe, E. B., Ahmed, A. 2000; 93 (3): 261-264
Abstract

Early recognition and prompt intervention are the most crucial steps in the management of gallstone-induced biliary disease. Many conditions can mimic the presentation of gallstone-induced complications. Therefore, participation of a clinically astute physician is essential in evaluating symptoms and interpreting diagnostic data in patients with symptomatic gallstones.

View details for Web of Science ID 000085880200002

View details for PubMedID 10728510
Cost-effective evaluation of acute viral hepatitis WESTERN JOURNAL OF MEDICINE Ahmed, A., Keeffe, E. B. 2000; 172 (1): 29-32
View details for Web of Science ID 000084858500020

View details for PubMedID 10695442
Novel endoscopic approach for removal of a rectal foreign body GASTROINTESTINAL ENDOSCOPY Ahmed, A., Cummings, S. A. 1999; 50 (6): 872-874
View details for Web of Science ID 000083941700034

View details for PubMedID 10570362
Overview of interferon therapy for chronic hepatitis C. Clinics in liver disease Ahmed, A., Keeffe, E. B. 1999; 3 (4): 757-773
Abstract

The future therapy for chronic hepatitis C will probably include measures to decrease hepatocellular injury along with multidrug combinations, including inhibitors of the hepatitis C viral protease, helicase, or polymerase to reduce serum levels or eradicate HCV RNA. The results of recently concluded trials of IFN-alpha 2b plus ribavirin combination therapy have shown a twofold improvement in the biochemical and virologic response rates and superiority by other measures of efficacy with an acceptable safety profile. In view of these results, new guidelines for the management of chronic HCV infection are appropriate (Fig. 1).

View details for PubMedID 11291249
The successful use of telemedicine in acute variceal hemorrhage JOURNAL OF CLINICAL GASTROENTEROLOGY Ahmed, A., Slosberg, E., Prasad, P., Keeffe, E. B., Imperial, J. C. 1999; 29 (2): 212-213
View details for Web of Science ID 000082193800027

View details for PubMedID 10478893
A novel technique for endoscopic removal of expandable biliary Wallstent GASTROINTESTINAL ENDOSCOPY Ahmed, A., Keeffe, E. B., Imperial, J. C. 1999; 50 (2): 279-281
View details for Web of Science ID 000081929400027

View details for PubMedID 10425430
Should we throw fat on the fire? Comment INFLAMMATORY BOWEL DISEASES Ahmed, A., Triadafilopoulos, G. 1999; 5 (3): 236-237
View details for Web of Science ID 000081909400015
Treatment strategies for chronic hepatitis C: Update since the 1997 National Institutes of Health Consensus Development Conference 1st University-of-California-San-Francisco/Stanford Asia Liver Symposium Ahmed, A., Keeffe, E. B. WILEY-BLACKWELL PUBLISHING, INC. 1999: S12–S18
Abstract

The National Institutes of Health Consensus Development Conference on the management of hepatitis C, which took place in March 1997 and was published in September 1997, established guidelines for the diagnosis and management of chronic hepatitis C. The recommended treatment of chronic hepatitis C virus (HCV) infection is interferon alpha (or equivalent) 3 MIU three times per week for 12 months, in patients showing response to therapy after 3 months. Patients with the greatest risk for progression to cirrhosis (i.e. persistently elevated alanine aminotransferase levels, detectable serum HCV-RNA and liver biopsy showing portal or bridging fibrosis and at least moderate inflammation and necrosis) are recommended as candidates for therapy. The indication for therapy is less obvious in patients with milder histological changes, compensated cirrhosis and age less than 18 years or older than 60 years. Treatment is not indicated for patients with persistently normal aminotransferases or decompensated cirrhosis. This review outlines the background studies that led to the recommendations of the National Institutes of Health for the treatment of chronic hepatitis C and reviews newer evolving treatment strategies over the past year. In particular, the results of studies exploring treatment options for relapsers and non-responders to prior interferon therapy and the reported results to date on the safety and efficacy of combination therapy with interferon plus ribavirin are highlighted. Although aggressive suppression of HCV-RNA with induction therapy (daily and/or higher doses) or long-acting pegylated interferon preparations may improve the current results of therapy, few data are yet available. Finally, the treatment of chronic hepatitis C with protease inhibitors holds promise but has yet to reach the stage of clinical trials.

View details for Web of Science ID 000081033600004

View details for PubMedID 10382632
Tuberculous peritonitis: Fatality associated with delayed diagnosis SOUTHERN MEDICAL JOURNAL Ahmad, M., Ahmed, A. 1999; 92 (4): 406-408
Abstract

We describe a fatal case of tuberculous peritonitis and review the literature on the diagnostic modalities available to diagnose this entity. We suspect a delayed diagnosis resulted in the death of our patient. Today, the prompt diagnosis of an unknown ascitic process involves laparoscopy. A patient with unknown large volume ascites is the easiest and safest to laparoscope. Using a mini laparoscope, a bedside procedure with instantaneous return can be done. The newer noninvasive tests like determination of ascites fluid adenosine deaminase activity and polymerase chain reaction may be helpful in the prompt diagnosis of peritoneal tuberculosis. We recommend that patients with clinical presentation suggestive of peritoneal tuberculosis have either an aggressive diagnostic workup using high-yield tests or a trial of antituberculous therapy.

View details for Web of Science ID 000079711100010

View details for PubMedID 10219360
An uncommon aetiology of perforated gastric ulcer POSTGRADUATE MEDICAL JOURNAL Ahmad, M., Vaidyan, P., Ahmed, A. 1999; 75 (880): 113-114
View details for Web of Science ID 000078440000017

View details for PubMedID 10448478
Lamivudine therapy for chemotherapy-induced reactivation of hepatitis B virus infection AMERICAN JOURNAL OF GASTROENTEROLOGY Ahmed, A., Keeffe, E. B. 1999; 94 (1): 249-251
Abstract

A 54-yr-old man with lymphoma and serological evidence of prior hepatitis B virus (HBV) infection, with detectable anti-HBc and anti-HBs, was treated with intensive chemotherapy. He had reactivation of HBV infection with acute hepatitis B manifest by detectable HBsAg and elevated aminotransferase levels >1000 IU/L. He was treated with lamivudine 150 mg daily and had prompt resolution of acute hepatitis B with return of elevated aminotransferases to normal, and initial loss of HBeAg with later loss of HBsAg. Lamivudine was continued during the course of further chemotherapy as prophylaxis against repeat HBV reactivation. Lamivudine is a nucleoside analogue that is a potent inhibitor of HBV reverse transcriptase and HBV replication. Lamivudine therapy should be considered for the treatment of HBV reactivation and might play a future role as preemptive therapy of HBV reactivation in patients with prior hepatitis B or chronic hepatitis B with inactive viral replication.

View details for Web of Science ID 000082426600048

View details for PubMedID 9934765
Asymptomatic elevation of aminotransferase levels and fatty liver secondary to heterozygous hypobetalipoproteinemia AMERICAN JOURNAL OF GASTROENTEROLOGY Ahmed, A., Keeffe, E. B. 1998; 93 (12): 2598-2599
View details for Web of Science ID 000077465200055

View details for PubMedID 9860439
Bloody diarrhea caused by Plesiomonas shigelloides proctitis in a human immunodeficiency virus-infected patient CLINICAL INFECTIOUS DISEASES Ahmad, M., Aggarwal, M., Ahmed, A. 1998; 27 (3): 657-657
View details for Web of Science ID 000075917900047

View details for PubMedID 9770179
Esophageal perforation from Maloney dilator following esophageal biopsy. Medicine and health, Rhode Island Aggarwal, M., Vaidyan, P. B., Ahmed, A. 1998; 81 (4): 144-145
View details for PubMedID 9597835
A fatal case of Rhodotorula meningitis in AIDS. Medicine and health, Rhode Island Ahmed, A., Aggarwal, M., Chiu, R., Ramratnam, B., Rinaldi, M., Flanigan, T. P. 1998; 81 (1): 22-23
View details for PubMedID 9473937
Esophageal perforation: A complication of nasogastric tube placement AMERICAN JOURNAL OF EMERGENCY MEDICINE Ahmed, A., Aggarwal, M., Watson, E. 1998; 16 (1): 64-66
View details for Web of Science ID 000071502300014

View details for PubMedID 9451317
Splenic rupture: An unusual complication of colonoscopy AMERICAN JOURNAL OF GASTROENTEROLOGY Ahmed, A., Eller, P. M., Schiffman, F. J. 1997; 92 (7): 1201-1204
Abstract

Splenic rupture is an uncommon complication of colonoscopy. A high index of suspicion is a crucial factor in the prompt diagnosis of this rare but potentially fatal complication. We report a case of splenic rupture diagnosed 3 days after a colonoscopy and requiring splenectomy. We also reviewed 17 reported cases of splenic rupture after colonoscopy, including our case. The presumed mechanisms of splenic rupture during colonoscopy are direct trauma to the spleen, excessive splenocolic ligament traction, and decrease in the relative mobility between the spleen and the colon. Of the 17 cases reviewed, 10 had polypectomy and/or biopsy performed during colonoscopy. Other probable risk factors are identified and tabulated. The hemodynamic status of the patient is the primary factor used to determine the therapeutic option. Computed tomographic (CT) scan of the abdomen reliably demonstrates well-contained splenic laceration and subcapsular hematoma, and differentiates these splenic complications from perisplenic clot and hemoperitoneum. Thus, CT scan may help decide which patients may be managed operatively or nonoperatively. Splenectomy is the operative procedure of choice for splenic rupture after colonoscopy. Conservative management includes broad spectrum antibiotics, intravenous fluids, blood transfusion, and close hemodynamic monitoring. The factors mandating further evaluation of persistent abdominal pain after colonoscopy are hemodynamic instability, clinical features of acute abdomen, leukocytosis, and/or acute anemia. The onset of abdominal pain associated with one or more of these critical factors is usually within 24 h after colonoscopy. An emergent CT scan of the abdomen is the modality of choice to further evaluate these clinical features, but intestinal perforation and external bleeding must first be excluded.

View details for Web of Science ID A1997XK10700029

View details for PubMedID 9219800
Does antecedent splenectomy alter the course of HIV infection? Medicine and health, Rhode Island Ahmed, A., Watson, E. N., Carpenter, C. C. 1996; 79 (9): 331-332
View details for PubMedID 8885630
Rupture of the spleen as the initial manifestation of Wilson's disease AMERICAN JOURNAL OF GASTROENTEROLOGY Ahmed, A., Feller, E. R. 1996; 91 (7): 1454-1455
View details for Web of Science ID A1996UW71200037

View details for PubMedID 8678016

Professor of Medicine (Gastroenterology and Hepatology) at the Stanford University Medical Center

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