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 Web of Science ID 000361497900040
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
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 Web of Science ID 000357014100005
View details for PubMedID 25902933
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
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
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
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 Web of Science ID 000349968200026
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 Web of Science ID 000349617000004
View details for PubMedID 25619871
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 Web of Science ID 000347720300014
View details for PubMedID 24804988
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
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
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
Abstract
Prior studies have detected hepatitis B virus (HBV) DNA polymerase mutations in treatment naïve patients. However, most of these studies used either direct PCR 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 using a line probe assay.In a prospective, cross-sectional study, we enrolled 198 treatment-naïve patients with chronic hepatitis B (52.5% male, mean age 41 y), from February 2009 through May 2011, from 3 gastroenterology and liver clinics in Northern California. Exclusion criteria included infection with hepatitis C or D viruses or HIV. 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 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-naïve patients with chronic hepatitis B, we detected mutations in HBV DNA polymerase in only 1%. Given the low prevalence of these mutations and the uncertain clinical significance of such quasi-species, routine HBV DNA polymerase mutation analysis cannot be recommended before initiation of antiviral therapy for treatment-naïve 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 Web of Science ID 000341119700026
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
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
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 Web of Science ID 000337690200011
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
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
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
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
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 Web of Science ID 000330585500029
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
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
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 Web of Science ID 000326888100003
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 ?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
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 Web of Science ID 000314633700011
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
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
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 ?-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
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 Web of Science ID 000309867800051
View details for PubMedID 23010744
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
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
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
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
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 Web of Science ID 000297880000006
View details for PubMedID 21890080
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 Web of Science ID 000296144000014
View details for PubMedID 21778896
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
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
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
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
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
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 Web of Science ID 000261653400026
View details for PubMedID 18975084
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
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
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
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
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 Web of Science ID 000239523200009
View details for PubMedID 16871572
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
