Faculty Bibliography

BACKGROUND AND AIMS/OBJECTIVE:Hepatology is experiencing major shifts in disease etiologies and raising demand for multidisciplinary care. However, a globally harmonized framework defining core training content remains lacking. We aimed to develop a globally informed expert consensus framework for the content of core hepatology training, in order to provide a structured foundation for curriculum development. METHODS:A two-round modified Delphi using the RAND/UCLA Appropriateness Method (RAM) was conducted. A comprehensive list of curriculum items was developed from international training standards, refined by a steering committee, and rated by a stratified international panel. Consensus was determined using medians and a disagreement index (DI), which classified curriculum items as essential, desirable, or optional. RESULTS:456 experts completed Round 1, of whom 78.7% also completed Round 2. Consensus was strongest for foundational knowledge and core diagnostic skills, including interpretation of abnormal liver function and liver screening test results, and non-invasive fibrosis assessment (both DI=0). Management of major liver diseases was consistently prioritized as essential. Procedures with the highest endorsement for independent performance were paracentesis, transient elastography, variceal screening, and endoscopic variceal therapy. Consensus was limited for conventional ultrasonography and advanced interventions, reflecting regional variability in resources and scope of practice. Most experts (79.1%) supported formal training in research methodology, and the median recommended fellowship length was 24 months. Subgroup differences were mainly observed in selected resource-dependent or highly specialized items. CONCLUSIONS:This global consensus offers a priority-stratified outline of core hepatology training content providing a practical foundation for curriculum development and staged implementation across diverse health systems. IMPACT AND IMPLICATIONS/UNASSIGNED:Our study provides a consensus-based, priority-stratified framework for core hepatology training content that may inform curriculum development and local adaptation, given the growing global burden of liver disease and the heterogeneity of training standards. This framework may support curriculum mapping and local adaptation for trainees, program directors, professional societies, and policymakers, including in settings where structured hepatology training pathways are still evolving. In practical terms, these findings may assist educators and institutions in reviewing and refining national curricula and training structures. However, specific implementation decisions, including accreditation requirements and procedural training standards, will need to be adapted to local regulatory and resource contexts. Recognizing that these recommendations are based on expert consensus rather than outcome data and may be variably implementable in resource-limited settings, the next steps are pilot implementation in diverse settings, evaluation of trainee and patient outcomes, and iterative revision, supported by coordinated efforts from societies, governments, and training institutions.

INTRODUCTION/UNASSIGNED:Chronic hepatitis B infection affects an estimated 258 million people globally. Mother-to-child transmission (MTCT) accounts for over one-third of new cases in endemic regions and almost invariably results in lifelong infection if acquired at birth. Over the past four decades, universal vaccination, hepatitis B immunoglobulin (HBIG), and maternal antiviral prophylaxis have substantially reduced MTCT. However, limited access to antiviral therapy and HBIG in resource-constrained settings continues to hinder elimination efforts. AREAS COVERED/UNASSIGNED:This review focuses on HBV in pregnancy and breastfeeding, with emphasis on maternal antiviral prophylaxis. It outlines epidemiology, maternal risk factors, and the limitations of vaccination and HBIG. Evidence supporting tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) is evaluated, alongside HBIG-free strategies and novel vaccine delivery platforms. Postpartum management, including hepatitis flares and the safety of breastfeeding during antiviral therapy, is also addressed. EXPERT OPINION/UNASSIGNED:Maternal antiviral prophylaxis with TDF, and increasingly TAF, is central to preventing mother-to-child transmission of hepatitis B. HBIG-free strategies, earlier treatment initiation, and improved vaccines may further reduce transmission, particularly in resource-limited settings. Achieving WHO 2030 elimination goals will require policy commitment, affordable access, and integration of HBV prevention into routine maternal - child health care.

BACKGROUND AND AIMS/OBJECTIVE:Accumulating data related to prevention, surveillance and treatment of chronic hepatitis B (CHB) provided the impetus for this updated guideline, using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. METHODS:The guideline was developed in compliance with the National Academy of Medicine standards. The guideline panel developed structured questions following the Population, Intervention Comparison, Outcomes (PICO) framework. The panel addressed 6 PICO questions covering prevention (maternal to infant transmission and horizontal transmission), surveillance for liver cancer (among hepatitis B surface antigen positive (HBsAg) persons co-infected with hepatitis C virus, hepatitis D virus and/or human immunodeficiency viruses and after HBsAg loss) and treatment (HBsAg positive persons in immune-tolerant or indeterminate phases as well as withdrawal of antiviral therapy), providing evidence-based recommendations on these topics. Four systematic reviews of the literature were conducted, and two existing systematic reviews were utilized to support the recommendations in this practice guideline. CONCLUSIONS:This evidence-based guideline provides updated recommendations to optimize the care of persons with CHB.

BACKGROUND:With rapid changes in the management landscape of chronic hepatitis B (CHB), this technical systematic review addresses four critical Population, Intervention, Comparator, Outcome (PICO) questions to provide guidance to the formulation of recommendations to the 2025 AASLD practice guidelines for management of CHB. METHODS:The review was reported in accordance with PRISMA guidelines. Outcomes were evaluated across four key PICOs: (1) antiviral therapy for prevention of horizontal HBV transmission in high-risk groups, (2) antiviral therapy versus observation for persons in the immune-tolerant phase, (3) discontinuation versus continuation of nucleos(t)ide analogue therapy in HBeAg-negative individuals with undetectable HBV DNA, and (4) hepatocellular carcinoma (HCC) surveillance in non-cirrhotic individuals with HBsAg clearance or co-infections with HCV, HDV, or HIV. RESULTS:For PICO 1, limited evidence suggests antiviral therapy may reduce horizontal transmission risk, though with low certainty. PICO 2 analyses reveal uncertain benefits of treating persons in the immune-tolerant phase, with very low certainty due to heterogeneity and bias. PICO 3 analyses demonstrate that discontinuing antiviral therapy in persons who are HBeAg negative with undetectable HBV DNA increases HBsAg loss rates (OR 12.65, 95% CI 1.58-101.51) but carries moderate risks of virologic relapse (OR 47.17, 95% CI 2.79-797.35), and clinical flares. PICO 4 analyses on several cohort studies showed that in patients co-infected with HCV, HBV, or HIV, annual incidence of HCC was higher than the level where screening becomes cost-effective, suggesting that regular liver cancer screening could be beneficial for these patients. CONCLUSIONS:Despite low certainty, the findings support shared decision-making in high-risk horizontal transmission scenarios or in treating individuals in the immune tolerance phase, caution in discontinuing antiviral therapy in virologically suppressed individuals without HBsAg loss, and tailored HCC surveillance for those with co-infection or cirrhosis.

BACKGROUND:Tenofovir alafenamide (TAF) has shown non-inferior efficacy to tenofovir disoproxil fumarate (TDF), with superior bone and renal safety. AIM/OBJECTIVE:To characterise 5-year TAF efficacy and safety in patients of East Asian ethnicity from pivotal Phase 3 studies. METHODS:Patients were randomised (2:1) to receive TAF or TDF for up to 3 years of double-blind treatment, followed by open-label TAF. Patients either continued TAF or switched from TDF to TAF at Week 96 (TDF → TAF 3 years) or Week 144 (TDF → TAF 2 years) of treatment. Efficacy endpoints (virologic, biochemical and serologic) and safety were assessed. RESULTS:Among 591 patients of East Asian ethnicity (TAF, n = 401; TDF → TAF 3 years, n = 84; TDF → TAF 2 years, n = 106), high rates of virologic control were achieved (89%, 94% and 92%, respectively) at Year 5 (missing = failure analysis). At Year 5, rates of alanine aminotransferase normalisation (85%, 90% and 78%) and hepatitis B e antigen loss (36%, 43% and 44%) were similar. Following the switch from TDF to TAF, changes in fasting lipid parameters were consistent with removal of the known lipid-lowering effect of TDF. However, changes in the total cholesterol to high-density lipoprotein ratio (marker of cardiovascular risk) were minimal and comparable in all groups by Year 5. Renal and bone parameters improved after switching. CONCLUSIONS:Through 5 years, rates of virologic suppression were high in East Asian patients treated with TAF or switched from TDF to TAF. TAF and TDF were well tolerated, with improved renal and bone safety observed in patients switching from TDF to TAF.

OBJECTIVE/UNASSIGNED:This study aimed to identify distinct intestinal microbiota associated with hepatocellular carcinoma (HCC) and to construct a predictive model for HCC. METHODS/UNASSIGNED:A case-control study was conducted including patients with chronic hepatitis B (CHB), liver cirrhosis (LC), HCC, and healthy controls (HC). Fecal 16S rDNA sequences were analyzed using bioinformatics approaches. Specific intestinal microbiota were identified through stratified analysis, and a predictive model was subsequently constructed. RESULTS/UNASSIGNED:were increased irrespective of liver disease stage. By combining microbiota profiles with clinical indicators, we developed a predictive nomogram that achieved an AUC of 0.865 in the training cohort and 0.848 in the external validation cohort. CONCLUSION/UNASSIGNED:Intestinal microbiota were associated not only with liver disease stage but also with the occurrence of HCC itself. Characteristic microbiota may serve as effective biomarkers for predicting HCC.

BACKGROUND:The association between isolated hepatitis B core antibody (HBcAb) positivity and chronic kidney disease (CKD) remains debated. While some studies suggest HBV infection increases CKD risk, others report inconclusive findings. This study evaluated the association between isolated HBcAb positivityand CKD in the U.S. METHODS:Data from adult participants in the NHANES 2017-2020 pre-pandemic cycle were analyzed based on prespecified eligibility criteria. Participants were categorized into isolated HBcAb positive and non-infected groups. Weighted means and percentages described participant characteristics, while logistic regression models evaluated the association between isolated HBcAb positive and CKD. Multivariate logistic regression identified CKD risk factors among isolated HBcAb positive individuals. RESULTS:Among 7,582 participants (7072 non- infected and 510 isolated HBcAb positive), CKD prevalence was higher in isolated HBcAb positive individuals (7.9% vs. 5.2%, P = 0.018). Unadjusted analyses showed isolated HBcAb positivity increased CKD risk (OR = 1.25, 95% CI: 1.04-1.50, P = 0.019). However, adjusted analyses revealed an inverse association (OR = 0.76, 95% CI: 0.60-0.98, P = 0.034). In isolated HBcAb positive individuals, older age (OR = 1.06, P = 0.017) and serum urea nitrogen (BUN) elevation (OR = 1.20, P = 0.001) were associated with higher CKD risk, while higher education lever reduced the risk (OR = 0.28, P = 0.030). CONCLUSION/CONCLUSIONS:Although CKD prevalence was higher in isolated HBcAb positive patients, There was no positive association between isolated HBcAb positivity and CKD. Older age and elevated BUN levels were significantly associated with higher CKD risk, while elevated education lever reduced the risk. These findings highlight the needs for individualized monitoring and management of at-risk HBV-infected patients when offering antiviral therapy and monitoring after clinical cure of hepatitis B.

BACKGROUND:Mothers with chronic hepatitis B and advanced fibrosis may require antiviral therapy throughout pregnancy. Current guidelines recommend tenofovir disoproxil fumarate (TDF), which is unsuitable for mothers at risk of renal dysfunction or decreased bone mineral density. AIMS/OBJECTIVE:This study aimed to evaluate the safety of tenofovir alafenamide (TAF) therapy during pregnancy. METHODS:Mothers with chronic hepatitis B treated with TAF or no therapy were retrospectively enrolled and categorised into three groups: (A) TAF-first trimester, (B) TAF-late trimester and (C) no treatment. Propensity score matching was applied to create comparable groups. Primary assessments included serious adverse events up to postpartum week 28, while secondary assessments examined predictors of such events and vertical transmission rates. RESULTS:Among 284 mothers, 160 were selected. No significant differences were observed in foetal loss, low birth weight, preterm delivery or congenital abnormalities between groups A and B, or between groups A and C. Other adverse events were similar across groups, except for a higher incidence of gestational diabetes in the TAF-first trimester group. In vitro fertilisation was identified as the sole predictor of serious events. No infants were reported with hepatitis B virus infection at 28 weeks postpartum. CONCLUSIONS:This study suggests that TAF treatment throughout pregnancy is safe for mothers with chronic hepatitis B and their infants. TAF therapy represents a viable treatment option for these mothers.

BACKGROUND:This study utilised the Global Burden of Disease data (2010-2021) to analyse the rates and trends in point prevalence, annual incidence and years lived with disability (YLDs) for major chronic liver diseases, such as hepatitis B, hepatitis C, metabolic dysfunction-associated liver disease, cirrhosis and other chronic liver diseases. METHODS:Age-standardised rates per 100,000 population for prevalence, annual incidence and YLDs were compared across regions and countries, as well as the socio-demographic index (SDI). Trends were expressed as percentage changes (PC) and estimates were reported with uncertainty intervals (UI). RESULTS:Globally, in 2021, the age-standardised rates per 100,000 population for the prevalence of hepatitis B, hepatitis C, MASLD and cirrhosis and other chronic liver diseases were 3583.6 (95%UI 3293.6-3887.7), 1717.8 (1385.5-2075.3), 15018.1 (13756.5-16361.4) and 20302.6 (18845.2-21791.9) respectively. From 2010 to 2021, the PC in age-standardised prevalence rates were-20.4% for hepatitis B, -5.1% for hepatitis C, +11.2% for MASLD and + 2.6% for cirrhosis and other chronic liver diseases. Over the same period, the PC in age-standardized incidence rates were -24.7%, -6.8%, +3.2%, and +3.0%, respectively. Generally, negative associations, but with fluctuations, were found between age-standardised prevalence rates for hepatitis B, hepatitis C, cirrhosis and other chronic liver diseases and the SDI at a global level. However, MASLD prevalence peaked at moderate SDI levels. CONCLUSIONS:The global burden of chronic liver diseases remains substantial. Hepatitis B and C have decreased in prevalence and incidence in the last decade, while MASLD, cirrhosis and other chronic liver diseases have increased, necessitating targeted public health strategies and resource allocation.