Where to Find our Published Work

Publications

Professor of Medicine (Gastroenterology and Hepatology) and, by courtesy, of Epidemiology and Population Health

Publications

  • Treatment eligibility in hepatitis B: a call for better linkage to optimal care LANCET GASTROENTEROLOGY & HEPATOLOGY Huang, D. Q., Nguyen, M. H. 2021; 6 (3): 160
  • Risk of hepatocellular carcinoma with tenofovir versus entecavir in chronic hepatitis B Reply LANCET GASTROENTEROLOGY & HEPATOLOGY Tseng, C., Hsu, Y., Nguyen, M. H. 2021; 6 (2): 87–88
  • Substantial gaps in evaluation and treatment of patients with hepatitis B in the US. Journal of hepatology Ye, Q., Kam, L. Y., Yeo, Y. H., Dang, N., Huang, D. Q., Cheung, R., Nguyen, M. H. 2021

    Abstract

    HBV associated liver complication is reduced by antiviral therapy. Prior studies using local institutional cohorts have suggested suboptimal evaluation and treatment. We aimed to determine the proportion of patients with chronic HBV infection who received adequate evaluation, were treatment eligible, and received antiviral treatment using a large, nationwide cohort.This retrospective analysis utlized claims data of approximately 73 million enrollees across the US from Optum's de-identified Clinformatics® Data Mart Database, 2003-2019. Adults with chronic HBV infection observed for ≥ 6 months before and after index chronic HBV infection diagnosis were identified via ICD-9/ICD-10 codes and confirmed by positive HBsAg, HBeAg or HBV DNA PCR.We included 12,608 eligible patients in the study analysis (mean age 45.7 years, 52.1% male, 54.6% Asian, 18.1% Caucasian, 10.5% African American). About half of the cohort (n=6,559, 52.3%) did not have a complete laboratory evaluation (defined as having HBeAg, HBV DNA, and ALT tests) and only 72.4% (n=9,129) had an "adequate" evaluation (at least HBV DNA and ALT) during the entire study period. Of those with an adequate evaluation, 11.2% were treatment eligible by AASLD criteria and 13.9% by EASL criteria; and of these, 60.4% of AASLD eligible patients and 54.3% of EASL eligible patients received treatment within 12 months from becoming eligible.Half of chronic HBV infection patients in the US with private insurance did not have a complete laboratory assessment. Over one third of treatment-eligible patients did not receive antiviral therapy. Patients who visited a GI/ID specialist had a higher chance of receiving adequate evaluation and treatment. Urgent intervention is needed to identify and address the barriers for these care gaps.In this study, we used a national database that includes laboratory data in addition to medical and pharmacy claims data to assess the current real-world situation of chronic HBV infection care in the US. Among the 12,608 patients with chronic HBV infection included in our study, 52.3% never had a complete laboratory and only 73% had adequate evaluation. Among those who were treatment eligible by AASLD or EASL guidelines, only 60.4% and 54.3% received treatment within 12 months, respectively.

    View details for DOI 10.1016/j.jhep.2021.08.019

    View details for PubMedID 34474097

  • Incidences and Determinants of Functional Cure during Entecavir or Tenofovir Disoproxil Fumarate for Chronic Hepatitis B. The Journal of infectious diseases Hsu, Y. C., Yeh, M. L., Wong, G. L., Chen, C. H., Peng, C. Y., Buti, M. n., Enomoto, M. n., Xie, Q. n., Trinh, H. n., Preda, C. n., Liu, L. n., Cheung, K. S., Yeo, Y. H., Hoang, J. n., Huang, C. F., Riveiro-Barciela, M. n., Kozuka, R. n., Istratescu, D. n., Tsai, P. C., Accarino, E. V., Lee, D. H., Wu, J. L., Huang, J. F., Dai, C. Y., Cheung, R. n., Chuang, W. L., Yuen, M. F., Wong, V. W., Yu, M. L., Nguyen, M. H. 2021

    Abstract

    Long-term incidences and baseline determinants of functional cure (HBsAg seroclearance) during entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment are incompletely understood.This is an international multicenter cohort study of treatment-naïve chronic hepatitis B (CHB) patients who initiated on ETV or TDF without baseline malignancy. Patients were observed for HBsAg seroclearance until death or loss to follow-up. We calculated the incidences and explored the baseline determinants of HBsAg seroclearance using competing risk regression.The analysis included 4,769 patients (median age, 50 years; 69.05% male), with a median follow-up of 5.16 years (26,614.47 person-years). HBsAg clearance occurred in 58 patients, yielding a 10-year cumulative incidence of 2.11% (95% CI, 1.54 -- 2.88%) and an annual rate of 0.22% (95% CI, 0.17--0.28%). Baseline predictors included low-level viremia with HBV DNA <2,000 IU/mL (adjusted sub-distribution HR [aSHR], 3.14; 95% CI, 1.80--5.49), elevated serum alanine aminotransferase (ALT) >200 U/L (aSHR, 3.68; 95% CI, 2.07--6.53), serum bilirubin (aSHR, 1.11 per mg/dL; 95% CI, 1.06--1.17), and fatty liver (aSHR, 1.84; 95% CI, 1.03--3.29).HBsAg seroclearance rarely occurs in CHB patients treated with ETV or TDF and is associated with low-level viremia, ALT flare, bilirubin level, and fatty liver.

    View details for DOI 10.1093/infdis/jiab241

    View details for PubMedID 33999179

  • Differential clinical characteristics and mortality outcomes in persons with NAFLD and/or MAFLD. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Nguyen, V. H., Le, M. H., Cheung, R. C., Nguyen, M. H. 2021

    Abstract

    Metabolic dysfunction-associated fatty liver disease (MAFLD) establishes new criteria for diagnosing fatty liver disease independent of alcohol intake and concomitant viral hepatitis infection. However, the long-term outcomes of patients with MAFLD are sparse. We aimed to describe the characteristics and long-term survival of persons meeting criteria for NAFLD only (non-MAFLD NAFLD), for both NAFLD and MAFLD (NAFLD-MAFLD), and for MAFLD only (non-NAFLD MAFLD).Using data from the third National Health and Nutrition Examination Survey (NHANES III) 1988 - 1994, 2997 participants with fatty liver identified via ultrasound were categorized into three distinct groups: non-MAFLD NAFLD, NAFLD-MAFLD, and non-NAFLD MAFLD.Participants in the NAFLD-MAFLD and non-NAFLD MAFLD groups were older, had more metabolic traits and higher mean liver enzymes. Nearly 8% of participants in the non-NAFLD MAFLD group had advanced fibrosis (FIB-4 >2.67) while only 1.3% and 1.9% in the NAFLD-MAFLD and non-MAFLD NAFLD groups did, respectively (P <0.0001). Non-NAFLD MAFLD participants had the highest cumulative incidence of all-cause mortality (26.2%) followed by those with NAFLD-MAFLD then non-MAFLD NAFLD participants (21.1% and 10.6%, respectively, P <0.0001). Similar findings were observed for cardiovascular disease (CVD)-related and other-cause (non-CVD, non-cancer) mortality. Non-NAFLD MAFLD was independently associated with all-cause mortality compared to non-MAFLD NAFLD (adjusted hazard ratios: 2.4, 95% CI: 1.2 - 4.6, P = 0.01).MAFLD criteria identified a significant group of people with more comorbidities and worse prognosis compared to those with NAFLD only. These criteria should be considered in the general population to identify high-risk groups for early interventions.

    View details for DOI 10.1016/j.cgh.2021.05.029

    View details for PubMedID 34033923

  • Treatment Algorithm for Managing Chronic Hepatitis B Virus Infection in the United States: 2021 Update. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Martin, P., Nguyen, M. H., Dieterich, D. T., Lau, D. T., Janssen, H. L., Peters, M. G., Jacobson, I. 2021

    Abstract

    Chronic hepatitis B (CHB) infection remains the most frequent etiology of hepatocellular carcinoma globally as well as a major cause of cirrhosis. Despite vaccination, substantial numbers of persons have already been infected with hepatitis B virus and remain at risk of progressive liver disease.In 2004, a CHB management algorithm was developed by a panel of North American hepatologists which was subsequently updated in 2006, 2008, and 2015. Since the most recent version, several developments have altered the management of CHB. Tenofovir alafenamide, with a more favorable safety profile than tenofovir disoproxil fumarate, has been introduced as an initial antiviral choice as well as an alternative for long-term therapy. Quantitation of hepatitis B surface antigen (HBsAg) is becoming more widely available in clinical practice, with implications for monitoring response to treatment. Additionally, there has been a shift in how the natural history of CHB is perceived as newer evidence has challenged the concept that during the immunotolerant phase of infection disease progression is not a concern. Finally, recent analyses indicate that in the United States, the average age of CHB patients has increased implying that the presence of comorbidities including metabolic liver disease increasing use of biologics associated with aging will increasingly affect disease management.This updated algorithm is intended to serve as a guide to manage CHB while new antiviral strategies are developed.Recommendations have been based on evidence from the scientific literature, when possible, as well as clinical experience and consensus expert opinion. Points of continued debate and areas of research need are also described.

    View details for DOI 10.1016/j.cgh.2021.07.036

    View details for PubMedID 34329775

  • ALT levels in Treatment-Naïve, Chronic Hepatitis B Patients with Concurrent Fatty Liver Disease: A U.S. Nationwide Study. Digestive diseases (Basel, Switzerland) Chang, C. Y., Kam, L., Dang, N., Cheung, R., Nguyen, M. H. 2021

    View details for DOI 10.1159/000518645

    View details for PubMedID 34348281

  • Progression Rates by Age, Sex, Treatment, and Disease Activity by AASLD and EASL Criteria: Data for Precision Medicine. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Park, J., Le, A. K., Tseng, T. C., Yeh, M. L., Jun, D. W., Trinh, H., Wong, G. L., Chen, C. H., Peng, C. Y., Kim, S. E., Oh, H., Kwak, M. S., Cheung, K. S., Toyoda, H., Hsu, Y. C., Jeong, J. Y., Yoon, E. L., Ungtrakul, T., Zhang, J., Xie, Q., Ahn, S. B., Enomoto, M., Shim, J. J., Cunningham, C., Jeong, S. W., Cho, Y. K., Ogawa, E., Huang, R., Lee, D. H., Takahashi, H., Tsai, P. C., Huang, C. F., Dai, C. Y., Tseng, C. H., Yasuda, S., Kozuka, R., Li, J., Wong, C., Wong, C. C., Zhao, C., Hoang, J., Eguchi, Y., Wu, C., Tanaka, Y., Gane, E., Tanwandee, T., Cheung, R., Yuen, M. F., Lee, H. S., Yu, M. L., Kao, J. H., Yang, H. I., Nguyen, M. H. 2021

    Abstract

    Antiviral treatment criteria are based on disease progression risk, and hepatocellular carcinoma (HCC) surveillance recommendations for patients with chronic hepatitis B (CHB) without cirrhosis is based on an annual incidence threshold of 0.2%. However, accurate and precise disease progression estimate data are limited. Thus, we aimed to determine rates of cirrhosis and HCC development stratified by age, sex, treatment status and disease activity based on the 2018 AASLD and 2017 EASL guidelines.We analyzed 18,338 patients (8914 treated; 9424 untreated) from 6 centers from the US and 27 centers from Asia Pacific countries. The Kaplan-Meier method was used to estimate annual progression rates to cirrhosis or HCC in person-years.The cohort was 63% male, with a mean age of 46.19 years, baseline cirrhosis of 14.3%, and median follow up of 9.60 years. By AASLD criteria, depending on age, sex, and disease activity, annual incidence rates ranged from 0.07%-3.94% for cirrhosis, from 0.04%-2.19% for HCC in patients without cirrhosis, and 0.40%-8.83% for HCC in patients with cirrhosis. Several subgroups of patients without cirrhosis including males younger than 40 and females younger than 50 had annual HCC risk near or exceeding 0.2%. Similar results were found using EASL criteria.There is great variability in CHB disease progression rates even among "lower risk" populations. Future CHB modeling studies, public health planning, and HCC surveillance recommendation should be based on more precise disease progression rates based on sex, age, disease activity, plus treatment status.

    View details for DOI 10.1016/j.cgh.2021.05.062

    View details for PubMedID 34089852

  • Outcomes of Sequential Therapy With Tenofovir Alafenamide After Long-term Entecavir. The American journal of gastroenterology Nguyen, M. H., Atsukawa, M., Ishikawa, T., Yasuda, S., Yokohama, K., Trinh, H. N., Arai, T., Fukunishi, S., Ogawa, E., Hsu, Y. C., Maeda, M., Dang, H., Tseng, C. H., Takahashi, H., Jun, D. W., Watanabe, T., Chuma, M., Nozaki, A., Kawada, N., Cheung, R., Enomoto, M., Takaguchi, K., Toyoda, H. 2021; 116 (6): 1264-1273

    Abstract

    Entecavir (ETV) and tenofovir alafenamide (TAF) are both first-line hepatitis B virus (HBV) therapies, but ETV-to-TAF switch outcome data are limited. We aimed to assess outcomes up to 96 weeks after ETV-to-TAF switch.ETV-treated (≥12 months) chronic hepatitis B patients switched to TAF in routine practice at 15 centers (United States, Korea, Japan, and Taiwan) were included. Primary outcome was complete viral suppression (CVS) rate (HBV DNA <20 IU/mL).We analyzed 425 eligible patients (mean age 60.7 ± 13.2 years, 60% men, 90.8% Asian, 20.7% with diabetes, 27% with hypertension, 14.8% with cirrhosis, 8.3% with hepatocellular carcinoma, and mean ETV duration before switch 6.16 ± 3.17 years). The mean baseline estimated glomerular filtration rate (eGFR) was 89 ± 19 (chronic kidney disease [CKD] stages: 55.6% stage 1, 35.7% stage 2, and 8.8% stages 3-5). CVS rate increased from 91.90% at switch (from 90.46% 24 weeks before switch) to 95.57% and 97.21% at 48 and 96 weeks after (P = 0.03 and 0.02, respectively). Over the 96 weeks after switch, mean HBV DNA (P < 0.001) but not alanine aminotransferase or CKD stage decreased. Between switch and 96-week follow-up, 11% (26/235) of CKD stage 1 patients migrated to stage 2 and 8% (12/151) of stage 2 patients to stages 3-5, whereas 18% (27/151) from stage 2 to 1, and 19% (7/37) from stages 3-5 to 2. On multivariable generalized estimated equation analysis adjusted for age, sex, hypertension, diabetes, and cirrhosis, baseline eGFR, age (P < 0.001), and CKD stages 2 and 3-5 (vs 1) (both P < 0.001) were associated with lower follow-up eGFR.After an average of 6 years on ETV, CVS increased from 91.9% at TAF switch to 97.2% at 96 weeks later.

    View details for DOI 10.14309/ajg.0000000000001157

    View details for PubMedID 34074829

  • The Changing Epidemiology of Liver Disease Among US Children and Adolescents From 1999 to 2016. The American journal of gastroenterology Li, J., Le, M. H., Barakat, M. T., Cheung, R. C., Nguyen, M. H. 2021

    Abstract

    Nonalcoholic fatty liver disease (NAFLD) and infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) are major causes of liver disease in adults. However, data for children and adolescents are limited. Our study aimed to characterize the prevalence, trend, and risk factors of infection of HBV and HCV and possible NAFLD for this population.We analyzed 6,647 children and adolescents (aged 6-21 years) from the 1999-2016 National Health and Nutrition Examination Survey.Among individuals aged 6-21 years, HBV prevalence decreased after 2011, from 0.72% in 1999-2004 and 0.85% in 2005-2010 to 0.27% in 2011-2016 (P < 0.001), whereas HCV prevalence increased to 0.26% in 2011-2016 after an initial decline from 0.15% in 1999-2004 to 0.02% in 2005-2010 (P = 0.01). Possible NAFLD prevalence also increased by approximately 40% in individuals aged 12-21 years, from 8.54% in 1999-2004 to 10.1% in 2005-2010 and then 11.8% in 2011-2016 (P = 0.033), with most possible NAFLD individuals being male, being obese, or having higher glucose, fasting insulin, hemoglobin A1c, homeostatic model assessment of insulin resistance, liver enzymes, lipids, and uric acid (all P < 0.01). On multivariate logistic regression, hypertension (odds ratio 4.79, 95% confidence interval 1.44-15.9) and dyslipidemia (odds ratio 11.6, 95% confidence interval 5.65-23.9) increased risk for possible NAFLD but not income:poverty ratio, hours spent on computer use, or added sugars.Although HBV prevalence has decreased in recent years among US children and adolescents, HCV and possible NAFLD have increased. Public health efforts must seek further understanding of the driving factors of this increase so that age-appropriate interventions can be developed and implemented.

    View details for DOI 10.14309/ajg.0000000000001386

    View details for PubMedID 34328446

  • Surveillance of patients with cirrhosis remains suboptimal in the United States. Journal of hepatology Yeo, Y. H., Hwang, J. n., Jeong, D. n., Dang, N. n., Kam, L. Y., Henry, L. n., Park, H. n., Cheung, R. n., Nguyen, M. H. 2021

    Abstract

    Regular monitoring/surveillance for liver complications is crucial in the management of patients with cirrhosis to reduce morbidity and mortality. Recommendations from professional societies are available but adherence is not well studied, especially outside of academic centers. We aimed to determine the frequencies and factors associated with laboratory monitoring, hepatocellular carcinoma (HCC) and esophageal varices (EV) surveillance in patients with cirrhosis.We identified 82,427 patients with cirrhosis (43,280 compensated and 39,147 decompensated) from the Truven Health MarketScan Research Database®, 2007-2016. We calculated the proportion of patients with cirrhosis with various frequencies of procedures/testing for laboratory (complete blood count, comprehensive metabolic panel, and prothrombin time), HCC and EV surveillance. We also used multivariable logistic regression to determine factors associated with having procedures.The proportions of patients undergoing HCC surveillance (8.78%), laboratory testing (29.72%) at least every 6-12 months, or EV surveillance (10.6%) at least every 1-2 years were suboptimal. The majority did not have HCC (45.4%) or EV (80.3%) surveillance during the entire study period. On multivariable regression, age 41-55 (vs. <41) years, PPO (vs. HMO) insurance plan, specialist care (vs. primary care and other specialties), diagnosis between 2013-2016 (vs. 2007-2009), decompensated (vs. compensated) cirrhosis, NAFLD (vs. viral hepatitis), and higher Charlson's comorbidity index were associated with significantly higher odds of undergoing procedures/testing every 6-12 months and EV surveillance every 1-2 years.Despite having modest improvement in the more recent years, routine monitoring and surveillance for patients with cirrhosis is suboptimal. Further efforts including provider awareness, patient education, and system/incentive-based quality improvement measures are urgently needed.Patients with cirrhosis should undergo health monitoring for liver complications to achieve early detection and treatment. In a large nationwide cohort of 82,427 patients with cirrhosis in the United States, we found a low rate of adherence (well less than half) to routine blood test monitoring and surveillance for liver cancer and esophageal varices (swollen blood vessels in the abdomen that could lead to fatal bleeding). Adherence has increased in the recent years, but much more improvement is needed.

    View details for DOI 10.1016/j.jhep.2021.04.042

    View details for PubMedID 33965477

  • Optimizing Hepatitis B Virus Screening in the United States Using a Simple Demographics-Based Model. Hepatology (Baltimore, Md.) Ramrakhiani, N. S., Chen, V. L., Le, M., Yeo, Y. H., Barnett, S. D., Waljee, A. K., Zhu, J., Nguyen, M. H. 2021

    Abstract

    Chronic hepatitis B (CHB) affects over 290 million people globally and only 10% have been diagnosed, presenting a severe gap that must be addressed. We developed logistic regression and machine learning (random forest) models to accurately identify patients with HBV, using only easily-obtained demographic data from a population-based data set.We identified participants with data on hepatitis B surface antigen (HBsAg), birth year, sex, race/ethnicity, and birthplace from 10 cycles of the National Health and Nutrition Examination Survey (NHANES, 1999-2018) and divided them into two cohorts: training (cycles 2, 3, 5, 6, 8, 10; n = 39,119) and validation (cycles 1, 4, 7, 9; n = 21,569). We then developed and tested our two models. The overall cohort was 49.2% male, 39.7% White, 23.2% Black, 29.6% Hispanic, and 7.5% Asian/Other, with a median birth year of 1973. In multivariable logistic regression, the following factors were associated with HBV infection: birth year 1991 or after (adjusted OR [aOR] of 0.28, P < 0.001), male sex (aOR 1.49, P = 0.0080), Black and Asian/Other vs. White (aOR 5.23 and 9.13, P < 0.001 for both), and being United States-born (vs. foreign-born) (aOR 0.14, P < 0.001). We found that the machine learning model consistently outperformed the logistic regression model, with higher AUROC values (0.83 vs. 0.75 in validation cohort, P < 0.001) and better differentiation of high and low risk individuals.Our machine learning model provides a simple, targeted approach to HBV screening, using only easily-obtained demographic data.

    View details for DOI 10.1002/hep.32142

    View details for PubMedID 34496066

  • Initial Evaluation, Long-Term Monitoring, and Hepatocellular Carcinoma Surveillance of Chronic Hepatitis B in Routine Practice: A Nationwide US Study. The American journal of gastroenterology Tran, S. n., Jeong, D. n., Henry, L. n., Cheung, R. C., Nguyen, M. H. 2021

    Abstract

    Previous studies, mostly small and single center, have shown gaps in the evaluation and monitoring of patients with chronic hepatitis B (CHB) virus infection. We aimed to examine the rates and predictors of adherence to guidelines for CHB care in a large nationwide cohort.We identified adult patients with CHB infection from the Truven MarketScan databases of commercially insured and Medicare patients with private insurance supplement (2007-2014) using International Classification of Diseases, Ninth Revision, Clinical Modification codes. The initial evaluation cohort had at least 6 months follow-up, whereas at least 12 months was required for the long-term monitoring cohort.We analyzed 55,317 eligible patients with CHB infection: mean age 46 ± 12 years, 58% men, and 14.8% with cirrhosis. Over a mean follow-up of 3.2 ± 2.3 years, 55.8% had specialist (gastroenterology or infectious diseases) visits. For initial evaluation, 59% of patients received both alanine aminotransferase (ALT) and hepatitis B virus (HBV) DNA tests, whereas only 33% had ALT, HBV DNA, and hepatitis B e antigen tests, with higher frequencies among patients with specialist visits. For long-term monitoring, only 25% had both ALT and HBV DNA tests performed annually. Among patients at higher risk of developing hepatocellular carcinoma (patients with cirrhosis, male patients without cirrhosis older than 40 years, and female patients without cirrhosis older than 50), less than 40% underwent annual hepatocellular carcinoma surveillance, with 25% never receiving surveillance during the study period. Predictors of optimal initial evaluation and long-term monitoring were compensated cirrhosis (odds ratio: 1.60 and 1.47, respectively) and specialist visits (odds ratio: 1.86 and 1.31, respectively) (both P < 0.001).In this large cohort of patients with CHB infection with private insurance or Medicare with private insurance supplement, we observed poor adherence to the recommended initial evaluation and long-term monitoring. Among the predictors of adherence were specialist visits. Further efforts are needed to identify barriers and improve access to care.

    View details for DOI 10.14309/ajg.0000000000001271

    View details for PubMedID 33927125

  • Prevalence of hepatic steatosis, fibrosis and associated factors in chronic hepatitis B. Alimentary pharmacology & therapeutics Zheng, Q., Zou, B., Wu, Y., Yeo, Y., Wu, H., Stave, C. D., Cheung, R. C., Nguyen, M. H. 2021

    Abstract

    As the prevalence of hepatitis steatosis (HS) increases, the prevalence of HS among those with chronic hepatitis B (CHB) may also be increasing but data on the effect of HS on CHB disease progression are lacking.To determine the prevalence of HS in CHB and associated factors, prevalence of fibrosis and its association with HS.Two researchers independently searched the literature and extracted data. We included full-length original articles of adults with CHB that evaluated. Prevalence estimates were pooled using a random-effects model. Associations between HS and fibrosis were assessed by pooled odds ratios (ORs) or mean differences (MD).Of the 2821 records screened, 54 eligible studies (28 648 patients) were analysed. The pooled prevalence of HS in CHB was 32.8% (95% CI, 28.9-37.0) with higher prevalence in men and obese patients. Older age, male sex and metabolic factors were associated with HS while an inverse association was observed between HS and HBeAg (OR 0.82, 95% CI, 0.75-0.91) and HBV DNA levels (MD -0.38, 95% CI -1.16--0.42). The pooled prevalence of significant fibrosis (≥F2 or ≥F3) was similar between patients with CHB with or without HS (40.1% vs 42.22%, P = 0.68). HS was not significantly associated with fibrosis (pooled OR 0.87, 95% CI 0.54-1.39, 20 studies, 6232 patients).Approximately 30% of patients with CHB had HS, which was positively associated with male sex, diabetes and metabolic factors, and was negatively associated with HBeAg and HBV DNA. HS was not significantly associated with increased fibrosis.

    View details for DOI 10.1111/apt.16595

    View details for PubMedID 34469587

  • Treatment eligibility in hepatitis B: a call for better linkage to optimal care. The lancet. Gastroenterology & hepatology Huang, D. Q., Nguyen, M. H. 2021; 6 (3): 160

    View details for DOI 10.1016/S2468-1253(20)30391-5

    View details for PubMedID 33581753

  • Risk of hepatocellular carcinoma with tenofovir versus entecavir in chronic hepatitis B - Authors' reply. The lancet. Gastroenterology & hepatology Tseng, C. H., Hsu, Y. C., Nguyen, M. H. 2021; 6 (2): 87–88

    View details for DOI 10.1016/S2468-1253(20)30395-2

    View details for PubMedID 33444533

  • Treatment and renal outcomes up to 96 weeks after tenofovir alafenamide switch from tenofovir disoproxil fumarate in routine practice. Hepatology (Baltimore, Md.) Toyoda, H. n., Leong, J. n., Landis, C. n., Atsukawa, M. n., Watanabe, T. n., Huang, D. Q., Liu, J. n., Quek, S. X., Ishikawa, T. n., Arai, T. n., Yokohama, K. n., Chuma, M. n., Takaguchi, K. n., Uojima, H. n., Senoo, T. n., Dang, H. n., Maeda, M. n., Hoang, J. n., Le, R. H., Yasuda, S. n., Thin, K. N., Tran, S. n., Chien, N. n., Henry, L. n., Asai, A. n., Fukunishi, S. n., Cheung, R. n., Lim, S. G., Trinh, H. N., Nguyen, M. H. 2021

    Abstract

    Real-world data for treatment effectiveness and renal outcomes in chronic hepatitis B (CHB) patients who were switched to the new and safer pro-drug, tenofovir alafenamide (TAF) from tenofovir disoproxil fumarate (TDF) are limited. Therefore, we aimed to evaluate treatment and renal outcomes of this population.We analyzed 834 CHB patients previously treated with TDF for ≥12 months who were switched to TAF in routine practice at 13 U.S. and Asia centers for changes in viral (HBV DNA <20 IU/mL), biochemical (ALT <35/25 U/L for male/ female) and complete (viral+biochemical) response; as well as estimated glomerular filtration rate (eGFR, mL/min/1.73 m2 ) up to 96-weeks after switch. Viral suppression (P<0.001) and ALT normalization (P=0.003) rates increased significantly after switch, as well as trend for increasing complete response (Ptrend =0.004) while eGFR trend (Ptrend >0.44) or mean eGFR (P>0.83, adjusted for age, sex, baseline eGFR, and diabetes, hypertension or cirrhosis by generalized linear modeling) remained stable. However, among those with baseline eGFR <90 (CKD stage ≥2), mean eGFR decreased significantly while on TDF (P=0.029) but not after TAF switch (P=0.90). By week 96, 21% (55/267) of patients with CKD stage 2 at switch improved to stage 1, 35% (30/85) of CKD stage 3-5 patients improved to stage 2 and 1.2% (1/85) to stage 1.Overall, we observed continued improvement in virologic response, ALT normalization, and no significant changes in eGFR following switch to TAF from TDF.

    View details for DOI 10.1002/hep.31793

    View details for PubMedID 33706421

  • Characteristics and healthcare costs in the aging hepatitis B population of Japan: A nationwide real-world analysis. Digestive diseases (Basel, Switzerland) Yotsuyanagi, H. n., Kurosaki, M. n., Yatsuhashi, H. n., Lee, I. H., Ng, A. n., Brooks-Rooney, C. n., Nguyen, M. H. 2021

    Abstract

    Advancing age, comorbidity, and financial burden have been observed in chronic hepatitis B (CHB) patients globally. As Japan is leading the world in aging demographics, similar real-world data are urgently needed for its CHB population to inform all stakeholders.This cross-sectional study characterized the demographics, comorbidities, and healthcare costs of a large Japanese real-world adult (≥18 years) CHB patient (ICD-10: B18.1) population from the Medical Data Vision database from 01/01/2012 to 31/12/2016. Comorbidities were identified by ICD-10 codes and the annual point-prevalence and Charlson Comorbidity Index (CCI) score were calculated. Annual mean and median all-cause healthcare utilization and costs per-patient were calculated. Comparison tests were conducted for CCI scores, prevalence of comorbidities and healthcare resource utilization and costs.We identified 11,125 CHB patients. Between 2012 and 2016, the mean age increased from 62.0±13.3 to 65.2±13.2 years, and the percentage of those aged ≥65 years increased from 45.6% to 60.7%. The prevalence of cirrhosis remained similar (5.8% in 2012 and 5.6% in 2016, p=0.69) while hepatocellular carcinoma decreased from 6.3% to 4.5% (p<0.01). The prevalence of non-liver comorbidities increased (40.9% to 52.0% for cancer (p<0.01), 12.1% to 17.7% for osteoporosis (p<0.01), and 10.7% to 15.0% for renal impairment (p<0.01). Healthcare resource utilization and costs also increased, with a 119.3% increase in the median total healthcare costs from ¥229,143 in 2012 to ¥502,467 in 2016 (p<0.01).The CHB population of Japan is predominantly elderly and carry a high non-liver comorbidity burden, while incurring increasing healthcare costs.

    View details for DOI 10.1159/000515854

    View details for PubMedID 33721872

  • Chronic hepatitis, osteoporosis, and men: under-recognised and underdiagnosed. The lancet. Diabetes & endocrinology Prasad, D. n., Nguyen, M. H. 2021; 9 (3): 141

    View details for DOI 10.1016/S2213-8587(21)00020-6

    View details for PubMedID 33607040

  • The epidemiology of NAFLD and lean NAFLD in Japan: a meta-analysis with individual and forecasting analysis, 1995-2040. Hepatology international Ito, T. n., Ishigami, M. n., Zou, B. n., Tanaka, T. n., Takahashi, H. n., Kurosaki, M. n., Maeda, M. n., Thin, K. N., Tanaka, K. n., Takahashi, Y. n., Itoh, Y. n., Oniki, K. n., Seko, Y. n., Saruwatari, J. n., Kawanaka, M. n., Atsukawa, M. n., Hyogo, H. n., Ono, M. n., Ogawa, E. n., Barnett, S. D., Stave, C. D., Cheung, R. C., Fujishiro, M. n., Eguchi, Y. n., Toyoda, H. n., Nguyen, M. H. 2021

    Abstract

    NAFLD is increasing in Asia including Japan, despite its lower obesity rate than the West. However, NAFLD can occur in lean people, but data are limited. We aimed to investigate the epidemiology of NAFLD in Japan with a focus on lean NAFLD.We searched PubMed, Cochrane Library, EMBASE, Web of Science, and the Japan Medical Abstracts Society (inception to 5/15/2019) and included 73 eligible full-text original research studies (n = 258,531). We used random-effects model for pooled estimates, Bayesian modeling for trend and forecasting, contacted authors for individual patient data and analyzed 14,887 (7752 NAFLD; 7135 non-NAFLD-8 studies) patients.The overall NAFLD prevalence was 25.5%, higher in males (p < 0.001), varied by regions (p < 0.001), and increased over time (p = 0.015), but not by per-person income or gross prefectural productivity, which increased by 0.64% per year (1983-2012) and is forecasted to reach 39.3% in 2030 and 44.8% in 2040. The incidence of NAFLD, HCC, and overall mortality were 23.5, 7.6 and 5.9 per 1000 person-years, respectively. Individual patient-level data showed a lean NAFLD prevalence of 20.7% among the NAFLD population, with lean NAFLD persons being older and with a higher all-cause mortality rate (8.3 vs. 5.6 per 1000 person-years for non-lean NAFLD, p = 0.02). Older age, male sex, diabetes, and FIB-4 were independent predictors of mortality, but not lean NAFLD.NAFLD prevalence has increased in Japan and may affect half of the population by 2040. Lean NAFLD individuals makeup 20% of the NAFLD population, were older, and had higher mortality.

    View details for DOI 10.1007/s12072-021-10143-4

    View details for PubMedID 33580453

  • Transition rates to cirrhosis and liver cancer by age, gender, disease and treatment status in Asian chronic hepatitis B patients. Hepatology international Liu, M. n., Tseng, T. C., Jun, D. W., Yeh, M. L., Trinh, H. n., Wong, G. L., Chen, C. H., Peng, C. Y., Kim, S. E., Oh, H. n., Kwak, M. S., Cheung, M. n., Toyoda, H. n., Hsu, Y. C., Jeong, J. Y., Yoon, E. L., Ungtrakul, T. n., Zhang, J. n., Xie, Q. n., Ahn, S. B., Enomoto, M. n., Shim, J. J., Cunningham, C. n., Jeong, S. W., Cho, Y. K., Ogawa, E. n., Huang, R. n., Lee, D. H., Takahashi, H. n., Tsai, P. C., Huang, C. F., Dai, C. Y., Tseng, C. H., Yasuda, S. n., Kozuka, R. n., Li, J. n., Wong, C. n., Wong, C. C., Zhao, C. n., Hoang, J. n., Eguchi, Y. n., Wu, C. n., Tanaka, Y. n., Gane, E. n., Tanwandee, T. n., Cheung, R. n., Yuen, M. F., Lee, H. S., Yu, M. L., Kao, J. H., Yang, H. I., Nguyen, M. H. 2021

    Abstract

    Increasing hepatitis-related mortality has reignited interest to fulfill the World Health Organization's goal of viral hepatitis elimination by 2030. However, economic barriers have enabled only 28% of countries to implement countermeasures. Given the high disease burden among Asians, we aimed to present age, sex, disease activity and treatment-specific annual progression rates among Asian chronic hepatitis B (CHB) patients to inform health economic modeling efforts and cost-effective public health interventions.We analyzed 18,056 CHB patients from 36 centers across the U.S. and seven countries/regions of Asia Pacific (9530 treated; 8526 untreated). We used Kaplan-Meier methods to estimate annual incidence of cirrhosis and hepatocellular carcinoma (HCC). Active disease was defined by meeting the APASL treatment guideline criteria.Over a median follow-up of 8.55 years, there were 1178 incidences of cirrhosis and 1212 incidences of HCC (297 without cirrhosis, 915 with cirrhosis). Among the 8526 untreated patients (7977 inactive, 549 active), the annual cirrhosis and HCC incidence ranged from 0.26% to 1.30% and 0.04% to 3.80% in inactive patients, and 0.55 to 4.05% and 0.19 to 6.03% in active patients, respectively. Of the 9530 treated patients, the annual HCC rates ranged 0.03-1.57% among noncirrhotic males and 2.57-6.93% among cirrhotic males, with lower rates for females. Generally, transition rates increased with age, male sex, the presence of fibrosis/cirrhosis, and active disease and/or antiviral treatment.Using data from a large and diverse real-world cohort of Asian CHB patients, the study provided detailed annual transition rates to inform practice, research and public health planning.

    View details for DOI 10.1007/s12072-020-10113-2

    View details for PubMedID 33394321

  • Natural History and Hepatocellular Carcinoma Risk in Untreated Chronic Hepatitis B Patients with Indeterminate Phase (117/120). Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Huang, D. Q., Li, X. n., Le, M. H., Le, A. K., Yeo, Y. H., Trinh, H. N., Zhang, J. n., Li, J. n., Wong, C. n., Wong, C. n., Cheung, R. C., Yang, H. I., Nguyen, M. H. 2021

    Abstract

    Many patients with chronic hepatitis B (CHB) may not conform to any of the defined phases, hence classified as indeterminate. We aimed to characterize the baseline prevalence of indeterminate patients and their natural history, phase transition and hepatocellular carcinoma (HCC) risk.This is a retrospective cohort study of 3,366 adult untreated non-cirrhotic CHB patients seen at five U.S. clinics and seven Taiwanese townships who had at least one year of serial laboratory data prior to enrollment with a mean follow-up of 12.5 years. Patients' clinical phases were determined at baseline and through serial data during follow-up, based on the AASLD 2018 Guidance.At baseline, 1,303 (38.7%) patients were in the indeterminate phase. By up to year 10 of follow-up, 686 patients (52.7%) patients remained indeterminate, while 283 (21.7%) became immune active. Compared to patients who remained inactive, patients who remained indeterminate had higher 10-year cumulative HCC incidence (4.6% vs. 0.5%, P<0.0001) and adjusted hazard ratio (HR) for HCC of 14.1 (P=0.03). Among patients who remained indeterminate, age ≥ 45 years (adjusted HR 18.4, P=0.005) was independently associated with HCC development.Nearly 40% of patients had indeterminate CHB phase. Of these, half remained indeterminate and one-fifth transitioned to the immune active phase. HCC risk in persistently indeterminate CHB was 14 times higher than inactive CHB. Among persistently indeterminate CHB patients, age ≥ 45 years was associated with 18 times higher risk for HCC development. Further studies are needed to evaluate the potential benefit of antiviral therapy for indeterminate patients, especially in the older subgroup.

    View details for DOI 10.1016/j.cgh.2021.01.019

    View details for PubMedID 33465482

  • Prevalence of Hepatitis B Vaccination Coverage and Serologic Evidence of Immunity Among US-Born Children and Adolescents From 1999 to 2016. JAMA network open Le, M. H., Yeo, Y. H., So, S., Gane, E., Cheung, R. C., Nguyen, M. H. 2020; 3 (11): e2022388

    Abstract

    Importance: The World Health Assembly has called for the elimination of hepatitis B and C by 2030. As hepatitis B has no cure, the US strategy to eliminate hepatitis B has focused on prevention through vaccination. However, there are limited data on the trend in vaccine-associated immunity since the US implementation of universal infant hepatitis B vaccination.Objective: To compare self-reported hepatitis B vaccination coverage among children and adolescents with serologic evidence of immunity and infection in the US from 1999 to 2016.Design, Setting, and Participants: This population-based cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2016. US-born persons aged 2 to 18 years without missing hepatitis B serologic test results and with reported vaccination history were included. Data were analyzed from September 2017 to June 2018.Main Outcomes and Measures: The proportion of participants who reported complete vaccination for hepatitis B and who had positive serologic test results indicating immunity.Results: Of 21 873 children and adolescents, 51.2%% were male, and the mean (SD) age was 10.6 (4.6) years. The survey reported that hepatitis B vaccination coverage increased significantly from 1999 to 2016 (from 62.6% [95% CI, 58.6%-66.4%] to 86.3% [95% CI, 82.9%-89.2%]; P<.001). Vaccine-associated immunity also increased from 1999 to 2016 among children aged 2 to 5 years (from 60.7% [95% CI, 48.8%-71.4%] to 65.2% [95% CI, 57.4%-72.3%]; P=.001) but decreased among children aged 6 to 10 years (from 64.6% [95% CI, 57.7%-70.9%] to 46.5% [95% CI, 39.1%-54.0%]; P<.001), adolescents aged 11 to 13 years (from 68.8% [95% CI, 58.1%-77.8%] to 26.2% [95% CI, 18.6%-35.5%]; P<.001), and adolescents aged 14 to 18 years (from 68.5% [95% CI, 62.9%-73.6%] to 15.6% [95% CI, 12.2%-19.8%]; P<.001). By birth year, serologic evidence of vaccine-associated immunity significantly decreased in the 1994-2003 NHANES birth cohort but not among those born between 1988 and 1993. Non-US-born children and adolescents did not show the same decreasing trend in immunity.Conclusions and Relevance: In this cross-sectional study, decreasing hepatitis B immunity was observed among US-born children and adolescents in the 1994-2003 NHANES birth cohort despite increasing rates of hepatitis B vaccination coverage. These findings suggest a possible need for surveillance and a booster vaccine dose for hepatitis B as those without serologic evidence of immunity become young adults and may engage in behaviors associated with an increased risk for infection.

    View details for DOI 10.1001/jamanetworkopen.2020.22388

    View details for PubMedID 33175174

  • Effects of Cirrhosis and Diagnosis Scenario in Metabolic-Associated Fatty Liver Disease-Related Hepatocellular Carcinoma HEPATOLOGY COMMUNICATIONS Chen, V. L., Yeh, M., Yang, J., Leong, J., Huang, D. Q., Toyoda, H., Chen, Y., Guy, J., Maeda, M., Tsai, P., Huang, C., Yasuda, S., Le, A. K., Dang, H., Giama, N. H., Ali, H. A., Zhang, N., Wang, X., Jun, D., Tseng, C., Hsu, Y., Huang, J., Dai, C., Chuang, W., Zhu, Q., Dan, Y., Schwartz, M., Roberts, L. R., Yu, M., Nguyen, M. H. 2020

    View details for DOI 10.1002/hep4.1606

    View details for Web of Science ID 000574610600001

  • ALT Levels for Asians With Metabolic Diseases: A Meta-analysis of 86 Studies With Individual Patient Data Validation HEPATOLOGY COMMUNICATIONS Huang, D. Q., Yeo, Y., Tan, E., Takahashi, H., Yasuda, S., Saruwatari, J., Tanaka, K., Oniki, K., Kam, L. Y., Muthiah, M. D., Hyogo, H., Ono, M., Barnett, S. D., Li, J., Zou, B., Fung, J., Lee, T., Wong, V., Yuen, M., Dan, Y., Lim, S., Cheung, R., Toyoda, H., Eguchi, Y., Nguyen, M. H. 2020

    View details for DOI 10.1002/hep4.1593

    View details for Web of Science ID 000570299500001

  • Incidence, Factors, and Patient-Level Data for Spontaneous HBsAg Seroclearance: A Cohort Study of 11,264 Patients CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY Yeo, Y., Tseng, T., Hosaka, T., Cunningham, C., Fung, J., Ho, H. J., Kwak, M., Trinh, H. N., Ungtrakul, T., Yu, M., Kobayashi, M., Le, A. K., Henry, L., Li, J., Zhang, J., Sriprayoon, T., Jeong, D., Tanwandee, T., Gane, E., Cheung, R. C., Wu, C., Lok, A. S., Lee, H., Suzuki, F., Yuen, M., Kao, J., Yang, H., Nguyen, M. H. 2020; 11 (9)
  • Liver Care and Surveillance: The Global Impact of the COVID-19 Pandemic HEPATOLOGY COMMUNICATIONS Toyoda, H., Huang, D. Q., Le, M. H., Nguyen, M. H. 2020

    View details for DOI 10.1002/hep4.1579

    View details for Web of Science ID 000556933200001

  • Prevalence of Chronic Hepatitis B Virus Infection in the United States. The American journal of gastroenterology Lim, J. K., Nguyen, M. H., Kim, W. R., Gish, R., Perumalswami, P., Jacobson, I. M. 2020

    Abstract

    Chronic hepatitis B virus (HBV) infection represents a major global health problem, affecting an estimated 257-291 million persons worldwide and is associated with substantial morbidity and mortality because of clinical complications, such as liver cirrhosis and hepatocellular carcinoma. Despite existing resources for vaccination, screening, and treatment, the burden of chronic HBV remains significant within the United States (US). Both the World Health Organization (WHO) and US Department of Health and Human Services (DHHS) have articulated formal hepatitis elimination plans, although an updated assessment of the epidemiology and prevalence of chronic HBV is needed to inform these initiatives. The Chronic Liver Disease Foundation (CLDF), a nonprofit 501(c)(3) educational organization dedicated to raising awareness of liver disease, partnered with a panel of leading US hepatologists to conduct an updated literature review to develop a contemporary HBV prevalence range estimate. Panel members researched and evaluated the peer-reviewed literature on HBV prevalence and, in May 2019, discussed their findings during a live HBV epidemiology workshop. The panel proposed an overall estimated prevalence for chronic HBV infection in the US of 1.59 million persons (range 1.25-2.49 million). This review provides a summary of the workshop findings and conclusions, which may serve to inform future initiatives focused on HBV screening and prevention in the US.

    View details for DOI 10.14309/ajg.0000000000000651

    View details for PubMedID 32483003

  • Pathologic Response to Pretransplant Locoregional Therapy is Predictive of Patient Outcome After Liver Transplantation for Hepatocellular Carcinoma Analysis From the US Multicenter HCC Transplant Consortium ANNALS OF SURGERY DiNorcia, J., Florman, S. S., Haydel, B., Tabrizian, P., Ruiz, R. M., Klintmalm, G. B., Senguttuvan, S., Lee, D. D., Taner, C., Verna, E. C., Halazun, K. J., Hoteit, M., Levine, M. H., Chapman, W. C., Vachharajani, N., Aucejo, F., Nguyen, M. H., Melcher, M. L., Tevar, A. D., Humar, A., Mobley, C., Ghobrial, M., Nydam, T. L., Amundsen, B., Markmann, J. F., Berumen, J., Hemming, A. W., Langnas, A. N., Carney, C. A., Sudan, D. L., Hong, J. C., Kim, J., Zimmerman, M. A., Rana, A., Kueht, M. L., Jones, C. M., Fishbein, T. M., Markovic, D., Busuttil, R. W., Agopian, V. G. 2020; 271 (4): 616–24
  • Prevalence of significant hepatic fibrosis using magnetic resonance elastography in a health check-up clinic population. Alimentary pharmacology & therapeutics Kang, K. A., Jun, D. W., Kim, M. S., Kwon, H. J., Nguyen, M. H. 2020; 51 (3): 388–96

    Abstract

    Significant hepatic fibrosis is associated with higher mortality. However, data on the estimated prevalence of liver fibrosis in the general population are scarce.To use magnetic resonance elastography (MRE) to investigate the prevalence of hepatic fibrosis in a Korean health check-up clinic cohort.We enrolled 2170 participants at our health check-up clinic between January 2015 and May 2018, all of whom had MR with chemical shift technique and MRE. The primary objective was to estimate the prevalence of liver fibrosis. For generalisation, sex- and age-standardised prevalence was calculated based on the Korean Statistical Information Service (KOSIS) during the period 2015-2018.The prevalence of F2 (≥3.0 kPa) and F3 (≥3.6 kPa) in the overall cohort was 5.1% and 1.3% respectively (sex- and age-adjusted prevalence of 3.8% and 1.3%). Non-alcoholic fatty liver disease (NAFLD) prevalence (>5% fat fraction) was 27.7% in the average risk population (after excluding alcohol use and viral hepatitis), and the prevalence of significant and advanced fibrosis in NAFLD participants was 8.0% and 1.5% respectively. In participants with diabetes, 12.5% had ≥F2 and 4.3% ≥F3. In participants with NAFLD plus diabetes, 24.1% had ≥F2 and 6.0% ≥F3. On multivariate analysis, only age, insulin, diabetes and fatty liver on MR were independently associated with significant fibrosis.In a Korean health check-up clinic setting, the prevalence of significant and advanced liver fibrosis was 5.1% and 1.3% (sex- and age-adjusted prevalence of 3.8% and 1.3%). The prevalence of advanced liver fibrosis was five times higher for diabetic participants with NAFLD.

    View details for DOI 10.1111/apt.15626

    View details for PubMedID 31943268

Akiko Mizuta
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