Clinical and Molecular Hepatology

SEVERE HEPATITIS B FLARE AND LIVER FAILURE – CURRENT ASSESSMENT AND MANAGEMENT: Seng Gee Lim, Maria Buti, Jordan J. Feld, James Fung, Adam J. Gehring, K. Rajender Reddy; Received February 4, 2026 Accepted March 11, 2026 Published online March 18, 2026; DOI: https://doi.org/10.3350/cmh.2026.0177 [Accepted]

Abstract
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Hepatitis B flare is a common complication of Chronic Hepatitis B (CHB) and is defined as an increase in HBV viral load associated with abnormal alanine aminotransferases (ALT), the consensus being an ALT≥5xupper limit of normal. The immunopathogenesis is related to induction of inflammatory cells and cytokines by the rise in HBV DNA. There are multiple causes of flares, and they carry the risk of progression to hepatic decompensation and acute-on-chronic liver failure (ACLF) with its associated mortality, potentially requiring liver transplantation. Initial assessment should be exclusion of other causes of liver dysfunction, determine severity, and prognosis. General prognostic models of ACLF are useful but the COSSH-ACLF II score is specific for HBV. Initiation of nucleos(t)ide analogues early is crucial and even in severe HBV flares reduces mortality by 73.6%. Once jaundice and coagulopathy occur, salvage by antivirals is challenging, and such patients should be considered for liver transplantation. However, many patients may not be suitable for transplant or may not have available donor livers as is common in Asia. Recently, there has been increasing evidence of benefit with adjunctive therapies such as corticosteroids and plasma exchange, but this needs to be balanced with the risks and should be considered as rescue therapies in severe HBV flares or ACLF. Liver transplant is the ultimate intervention when these other strategies fail to rescue patients. In summary, HBV flares are clinically serious events that can lead to hepatic decompensation and ACLF but strategies for rescue should be considered before liver transplantation.

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Hepatitis B in Africa: Progress toward World Health Organization 2030 targets, persistent disparities, and COVID-19 setbacks: Kui Wang, Ruchen Zhou; Clin Mol Hepatol 2026;32(2):e211-e215.
Published online March 11, 2026; DOI: https://doi.org/10.3350/cmh.2026.0151

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Seroepidemiology of hepatitis B virus infection in apparently healthy adults in China: a nationwide study based on 17 million check-up adults: Sailimai Man, Zhuoyan Yu, Jing Du, Jun Lv, Gang Li, Liming Li, Bo Wang; Clin Mol Hepatol 2026;32(2):e199-e204.
Published online March 4, 2026; DOI: https://doi.org/10.3350/cmh.2026.0047

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Extrahepatic mortality associated with chronic liver disease with or without cirrhosis from 2014 to 2024: Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, Aijaz Ahmed; Clin Mol Hepatol 2026;32(2):e194-e198.
Published online February 25, 2026; DOI: https://doi.org/10.3350/cmh.2026.0225

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From Metabolites to Chromatin: ACSS2-Driven Acetyl-CoA Fuels H3K27ac Chromatin Remodeling in HBV-Associated HCC: Hyeong-Jin Cho, Sung-Gyoo Park; Received January 23, 2026 Accepted January 24, 2026 Published online February 2, 2026; DOI: https://doi.org/10.3350/cmh.2026.0114 [Accepted]

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Correspondence to editorial on "New Insights into Antibody-Mediated NK Cell Immunity in Hepatitis B": Libo Tang, Yuhao Wang, Zihan Jin, Shihong Zhong, Yongyin Li; Received January 20, 2026 Accepted January 24, 2026 Published online February 2, 2026; DOI: https://doi.org/10.3350/cmh.2026.0096 [Accepted]

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Correspondence to letter regarding "From Immune Reshaping to Functional Cure: Translational Considerations for NK Cell Therapy in HBV": Zihan Jin, Libo Tang, Yuhao Wang, Shihong Zhong, Yongyin Li; Received January 20, 2026 Accepted January 24, 2026 Published online February 2, 2026; DOI: https://doi.org/10.3350/cmh.2026.0095 [Accepted]

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Treatment strategies for patients with hepatitis B virus infection coexisting with hepatitis C virus or metabolic dysfunction-associated steatotic liver disease: Chieh Liu, Yi-Fen Shih, Chun-Jen Liu; Clin Mol Hepatol 2026;32(2):565-579.
Published online January 9, 2026; DOI: https://doi.org/10.3350/cmh.2025.1227

Abstract
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Hepatitis B virus (HBV) remains a major cause of chronic liver diseases, especially in the Asia-Pacific region. In recent decades, coinfection with hepatitis C virus (HCV) and coexistence with metabolic dysfunction-associated steatotic liver disease (MASLD) have emerged as significant clinical concerns among HBV-infected patients. Although global HBV vaccination programs and curative therapies for HCV have led to a marked decline in HBV/HCV coinfection, MASLD is rapidly becoming the predominant comorbidity due to the global surge in metabolic risk factors. HBV/HCV coinfection typically results in more severe liver damage, with unique challenges in antiviral treatment and risk of HBV reactivation post-HCV clearance. In contrast, HBV/MASLD overlap demonstrates complex metabolic-viral interactions that may influence viral replication, hepatitis B surface antigen seroclearance, fibrosis progression, and risk of hepatocellular carcinoma. This review critically compares the epidemiology, clinical outcomes, and management strategies of HBV patients with concurrent HCV or MASLD, while addressing current research gaps and proposing directions for future investigations.

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Dissecting antibody-mediated natural killer cell effects reveals a cytotoxic CX3CR1⁺KLRC2^–CD16^hi subset linked to hepatitis B virus outcomes: Libo Tang, Yuhao Wang, Zihan Jin, Yurong Gu, Zhaofeng Zeng, Linnan Song, Xuan Yi, Lingtao Zhang, Yujing Zhang, Weiying He, Liping Wang, Weixin He, Jianru Sun, Xiaoqin Lan, Xiangyong Li, Shihong Zhong, Yongyin Li; Clin Mol Hepatol 2026;32(2):683-705.
Published online December 19, 2025; DOI: https://doi.org/10.3350/cmh.2025.0842

Background/Aims
Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment.
Methods
A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets.
Results
The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16^hiNK subpopulation (CX3CR1⁺KLRC2^–CD16^hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1⁺KLRC2^–CD16^hi subset tended to exhibit functional restoration in HBsAg-loss individuals.
Conclusions
Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1⁺KLRC2^–CD16^hiNK subset as a potential therapeutic target.

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Mechanisms and management of pegylated interferon-α toxicity in chronic hepatitis B
Liya Zhu, Fei Peng, Dingfang Pi, Jinzhi Lu
Frontiers in Immunology.2026;[Epub] CrossRef

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Acetyl-coenzyme A synthetase 2-mediated acetyl-coenzyme A accumulation promotes mitophagy and tumor growth via increased H3K27ac in hepatitis B virus-related hepatocellular carcinoma: Shan Li, Jie Hu, Yihan Yan, Xinrui Liu, Xiao Dong, Huijun Liang, Xin Tang, Junji Tao, Rong Zhang, Yuan Hu, Ailong Huang, Kai Wang, Ni Tang; Clin Mol Hepatol 2026;32(2):661-682.
Published online December 19, 2025; DOI: https://doi.org/10.3350/cmh.2025.0754

Background/Aims
Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial.
Methods
A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining.
Results
Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth.
Conclusions
These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.

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Targeting the innate immune system in treating hepatitis B: prospects for functional cure: Karen Cheuk-Ying Ho, Rex Wan-Hin Hui, Wai-Kay Seto, Man-Fung Yuen, Lung-Yi Mak; Clin Mol Hepatol 2026;32(1):184-199.
Published online November 11, 2025; DOI: https://doi.org/10.3350/cmh.2025.0935

Abstract
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Chronic hepatitis B (CHB) infection remains a significant global public health concern. Functional cure, defined as hepatitis B surface antigen seroclearance with unquantifiable HBV DNA at 24 weeks off treatment, is a desirable endpoint in the treatment of CHB, yet challenging to achieve. Given the limitations of current therapies including nucleos(t)ide analogues and pegylated interferon alpha, novel agents targeting functional cure are emerging. As hepatitis B virus (HBV) is a non-cytolytic virus, liver damage stems from the host immune response towards HBV-infected cells. The innate immune response during the initial phase of HBV infection is crucial in establishing an adequate level of immunity against the virus. However, HBV adopts various mechanisms to evade the host’s innate immunity, partly contributing to the chronicity of infection. This article provides a comprehensive review on how the HBV life cycle interacts with the host’s innate immune system. The latest evidence of novel agents targeting the innate immunity will also be covered. Retinoic acid inducible gene I agonists, toll-like receptor agonists, and interferons are therapies that target the HBV evasion strategies against host’s innate immunity. While small interfering RNAs and antisense oligonucleotides are originally designed for antigen knockdown and reinvigoration of the adaptive immune response, they have also shown additional impacts on the innate immunity. With ongoing research and innovation in combination strategies, advancement in the management of CHB is anticipated in the future.

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Current Status and Prospects of Clinical Research on Low-Level Viremia in Chronic Hepatitis B after Treatment
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Advances in Clinical Medicine.2026; 16(03): 1942. CrossRef

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Redefining MTCT prevention strategies toward HBV elimination: Correspondence to editorial on “Factors associated with hepatitis B mother-to-child transmission in a national prevention program”: Moran Ki, Jong-Hyun Kim; Clin Mol Hepatol 2026;32(2):e224-e226.
Published online July 28, 2025; DOI: https://doi.org/10.3350/cmh.2025.0805

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Reply to correspondence on “Factors associated with hepatitis B mother-to-child transmission in a national prevention program”
Eunho Choi, Ji Hoon Kim, Young-Sun Lee
Clinical and Molecular Hepatology.2026; 32(2): e262. CrossRef

2,118 View
47 Download
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Contemporary trends in extrahepatic mortality of chronic liver disease in the United States from 2014 to 2023: Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, Aijaz Ahmed; Clin Mol Hepatol 2026;32(1):e24-e28.
Published online July 28, 2025; DOI: https://doi.org/10.3350/cmh.2025.0802

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Impact of Documented Social Vulnerability on Clinical Outcomes in Metabolic Dysfunction‐Associated Steatotic Liver Disease
Pojsakorn Danpanichkul, Yanfang Pang, Maria Inggriani, Supapitch Sirimangklanurak, Matheus Souza, Ahmad Anouti, Andrew F. Ibrahim, Nikki Duong, Thomas G. Cotter, Thomas A. Kerr, Donghee Kim, Mazen Noureddin, Karn Wijarnpreecha
Liver International.2026;[Epub] CrossRef
Improved survival and reduced alcohol‐associated hepatitis risk with renin‐angiotensin‐aldosterone system inhibitors in alcohol‐associated liver disease
Pojsakorn Danpanichkul, Yanfang Pang, Donghee Kim, Andrew F. Ibrahim, Primrose Tothanarungroj, Omar Al Ta'ani, Narathorn Kulthamrongsri, Kwanjit Duangsonk, Robert J. Wong, Daniel Q. Huang, Karn Wijarnpreecha, Mazen Noureddin, Suthat Liangpunsakul
Alcohol, Clinical and Experimental Research.2026;[Epub] CrossRef
Extrahepatic mortality associated with chronic liver disease with or without cirrhosis from 2014 to 2024
Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, Aijaz Ahmed
Clinical and Molecular Hepatology.2026; 32(2): e194. CrossRef
The global epidemiology of alcohol-associated liver disease
Pojsakorn Danpanichkul, Francisco Idalsoaga, Frank Murray, Juan Pablo Arab, Luis Antonio Díaz
Hepatology Communications.2026;[Epub] CrossRef

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Breaking the chain of perinatal hepatitis B transmission: Editorial on “Factors associated with hepatitis B mother-to-child transmission in a national prevention program”: Shang-Chin Huang, Jia-Horng Kao; Clin Mol Hepatol 2026;32(2):946-948.
Published online July 28, 2025; DOI: https://doi.org/10.3350/cmh.2025.0801

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Global strategies and actions to eliminate hepatitis B virus infection: Chih-Lin Lin, Jia-Horng Kao; Clin Mol Hepatol 2025;31(4):1197-1212.
Published online July 28, 2025; DOI: https://doi.org/10.3350/cmh.2025.0492

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Through the implementation of hepatitis B vaccination and effective antiviral treatment over the past four decades, the hepatitis B surface antigen (HBsAg) seroprevalence of the vaccinated generation dramatically decline. The incidence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) also decreases. However, the elimination of HBV is still a challenge to achieve. Novel HBV biomarkers, including quantitative HBsAg, hepatitis B virus core-related antigen and HBV RNA are promising in predicting clinical phases, risks of disease progression and HBV functional cure. Current antiviral therapies, nucleoside/nucleotide and pegylated alpha-interferon, effectively decrease HCC incidence in chronic hepatitis B (CHB) patients and minimize the recurrence of HCC in patients receiving curative therapy. Novel agents under development to achieve HBV cure include direct-acting antivirals that target various stages of the HBV lifecycle and host targeting agents that enhance HBV-specific immunity. The action plans for eliminating hepatitis B in the future are universal HBV screening, early and simplified treatment as well as precision lifelong management for CHB patients. This narrative review will summarize and discuss global strategies and initiatives aimed at eliminating HBV infection.

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Insight into the Biology of Hepatitis B Virus and Recent Therapeutic Approaches
Prashant Tiwari, Istuti Saraswat, Jyoti Gupta
Current Microbiology.2026;[Epub] CrossRef
Refining surveillance of hepatocellular carcinoma in chronic hepatitis B through biomarker-based risk stratification
Tai-Chung Tseng, Shang-Chin Huang, Jia-Horng Kao
Hepatology Communications.2026;[Epub] CrossRef
Primary Liver Cancer Trends Worldwide and in China: Analysis of GLOBOCAN 2022 Data and Disease Management Implications
Jiayan Yan, Jiayi Wang, Jian Fan, Xinyi Cui, Yuxi Zhang, Xinrong Yang, Qiang Gao, Zhenbin Ding, Zhaoyou Tang, Jia Fan, Dan G. Duda, Ao Huang, Jian Zhou
Portal Hypertension & Cirrhosis.2026; 5(1): 65. CrossRef
Exploration and optimization of indole derivatives as novel anti-HBV agent with potential TLR7-agonistic effect
Lihua Yang, Zibin Qiu, Xincheng Li, Jiachen Wei, Yike Ma, Weiqun Yuan, Qiuting Xu, Xiaoke Gu, Jingying Qiu
Bioorganic & Medicinal Chemistry.2026; 138: 118662. CrossRef
Hepatitis B in Africa: Progress toward World Health Organization 2030 targets, persistent disparities, and COVID-19 setbacks
Kui Wang, Ruchen Zhou
Clinical and Molecular Hepatology.2026; 32(2): e211. CrossRef
Aspirin Use and Risk of HCC and Gastrointestinal Bleeding in Patients With HBV‐Related Cirrhosis: A Landmark Analysis
Mi Na Kim, Geun U. Park, Seng Chan You, Jae Seung Lee, Hye Won Lee, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn
Journal of Gastroenterology and Hepatology.2025; 40(11): 2750. CrossRef

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5 Web of Science
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Redefining MTCT prevention strategies toward HBV elimination: Editorial on “Factors associated with hepatitis B mother-to-child transmission in a national prevention program”: Eunho Choi, Ji Hoon Kim, Young-Sun Lee; Clin Mol Hepatol 2026;32(2):943-945.
Published online July 14, 2025; DOI: https://doi.org/10.3350/cmh.2025.0747

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Reply to correspondence on “Factors associated with hepatitis B mother-to-child transmission in a national prevention program”
Eunho Choi, Ji Hoon Kim, Young-Sun Lee
Clinical and Molecular Hepatology.2026; 32(2): e262. CrossRef
Redefining MTCT prevention strategies toward HBV elimination: Correspondence to editorial on “Factors associated with hepatitis B mother-to-child transmission in a national prevention program”
Moran Ki, Jong-Hyun Kim
Clinical and Molecular Hepatology.2026; 32(2): e224. CrossRef

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2 Web of Science
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Reconsidering the role of plasma pgRNA in NUC-treated CHB: Stratified biomarker interpretation and the limits of current assays: Letter to the editor on “Longitudinal profile of plasma pregenomic RNA in patients with chronic hepatitis B infection on long-term nucleoside analogues and its interaction with clinical parameters”: Xu Han, Jun Sun, Yinyan Li; Clin Mol Hepatol 2026;32(2):e131-e133.
Published online July 9, 2025; DOI: https://doi.org/10.3350/cmh.2025.0642

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Factors associated with hepatitis B mother-to-child transmission in a national prevention program: Moran Ki, Byung-Woo Kim, Dahye Baik, Jong-Hyun Kim; Clin Mol Hepatol 2025;31(4):1298-1315.
Published online June 24, 2025; DOI: https://doi.org/10.3350/cmh.2025.0214

Background/Aims
Hepatitis B virus (HBV) mother-to-child transmission (MTCT) remains a global health concern, with over 90% of perinatal infections leading to chronic HBV. To evaluate long-term trends in MTCT rates and associated factors within Korea’s national program.
Methods
Population-based cohort study using linked data from the Perinatal Hepatitis B Prevention Program (PHBPP) and National Health Insurance Service in Korea. The study included HBsAg-positive mother-infant pairs with post-vaccination serologic results from 2002 to 2021.
Results
Among the 154,478 mother-infant pairs, the overall MTCT rate after prophylaxis was 2.3%. Antiviral use lowered MTCT rates (0.9% vs. 2.4%) particularly in HBeAg-positivity (1.0% vs. 5.9%; adjusted odds ratio [aOR] 0.21; 95% confidence interval [CI] 0.14–0.32). Lower MTCT rates were observed for cesarean section vs. vaginal delivery (1.9% vs. 2.6%; aOR 0.78; 95% CI 0.73–0.84) and breastfeeding vs. formula feeding (1.8% vs. 2.8%; aOR 0.65; 95% CI 0.56–0.76). Annual MTCT rates decreased from 3.6% (2002–2005) to 1.3% (2018–2021). Antivirals reduced MTCT rates; initiation at 14–27 weeks (0.39%), or 28–32 weeks (0.44%) vs. ≥33 weeks (1.47%); postpartum continuation (0.55%) vs. antepartum discontinuation (1.44%); use ≥61 days (0.51%) vs. 1–60 days (1.67%). Lower MTCT risk was associated with maternal (old age, high income) and infant (female sex, preterm birth) factors.
Conclusions
This comprehensive analysis of the PHBPP in Korea demonstrates that the use of antivirals, breastfeeding, and cesarean section, combined with conventional immunoprophylaxis, has significantly reduced MTCT rates. These results are crucial for global HBV elimination and can help to guide HBV MTCT prevention strategies.

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Redefining MTCT prevention strategies toward HBV elimination: Editorial on “Factors associated with hepatitis B mother-to-child transmission in a national prevention program”
Eunho Choi, Ji Hoon Kim, Young-Sun Lee
Clinical and Molecular Hepatology.2026; 32(2): 943. CrossRef
Redefining MTCT prevention strategies toward HBV elimination: Correspondence to editorial on “Factors associated with hepatitis B mother-to-child transmission in a national prevention program”
Moran Ki, Jong-Hyun Kim
Clinical and Molecular Hepatology.2026; 32(2): e224. CrossRef
Breaking the chain of perinatal hepatitis B transmission: Editorial on “Factors associated with hepatitis B mother-to-child transmission in a national prevention program”
Shang-Chin Huang, Jia-Horng Kao
Clinical and Molecular Hepatology.2026; 32(2): 946. CrossRef
Reply to correspondence on “Factors associated with hepatitis B mother-to-child transmission in a national prevention program”
Eunho Choi, Ji Hoon Kim, Young-Sun Lee
Clinical and Molecular Hepatology.2026; 32(2): e262. CrossRef

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Reply to correspondence on “Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues”: Heejoon Jang, Won Kim; Clin Mol Hepatol 2026;32(2):e254-e256.
Published online June 9, 2025; DOI: https://doi.org/10.3350/cmh.2025.0533

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Advancing metabolic risk profiling in chronic hepatitis B: Reply to correspondence on “Metabolic health in antiviral era of chronic hepatitis B”: Shang-Chin Huang, Jia-Horng Kao; Clin Mol Hepatol 2026;32(1):e117-e118.
Published online May 13, 2025; DOI: https://doi.org/10.3350/cmh.2025.0500

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Correspondence to editorial 1 on “Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues”: Rui Huang, Mindie H. Nguyen; Clin Mol Hepatol 2026;32(1):e83-e84.
Published online May 8, 2025; DOI: https://doi.org/10.3350/cmh.2025.0479

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Advancing metabolic risk profiling in chronic hepatitis B: Reply to correspondence on “Metabolic health in antiviral era of chronic hepatitis B”
Shang-Chin Huang, Jia-Horng Kao
Clinical and Molecular Hepatology.2026; 32(1): e117. CrossRef

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Correspondence to editorial 2 on “Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues”: Rui Huang, Mindie H. Nguyen; Clin Mol Hepatol 2026;32(1):e85-e86.
Published online May 8, 2025; DOI: https://doi.org/10.3350/cmh.2025.0478

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Reply to correspondence on “Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues”
Heejoon Jang, Won Kim
Clinical and Molecular Hepatology.2026; 32(2): e254. CrossRef

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18 Download
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Non-infectivity of hepatitis B virus under nucleoside analog therapy revealed through auxiliary partial orthotopic liver transplantation: Xiaojie Chen, Guiwen Guan, Lin Wei, Jidong Jia, Xiangmei Chen, Fengmin Lu, Zhijun Zhu; Clin Mol Hepatol 2025;31(3):e263-e267.
Published online May 8, 2025; DOI: https://doi.org/10.3350/cmh.2025.0393

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Type 2 diabetes as a key metabolic risk factor for adverse outcomes in nucleos(t)ide analogue-treated chronic hepatitis B: Editorial on “Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues”: Heejoon Jang, Won Kim; Clin Mol Hepatol 2026;32(1):426-428.
Published online April 28, 2025; DOI: https://doi.org/10.3350/cmh.2025.0430

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Correspondence to editorial 2 on “Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues”
Rui Huang, Mindie H. Nguyen
Clinical and Molecular Hepatology.2026; 32(1): e85. CrossRef

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56 Download
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Correspondence to editorial on “Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial”: Hyung Joon Yim, Seong Hee Kang, Young Kul Jung, Jin Mo Yang; Clin Mol Hepatol 2026;32(1):e55-e57.
Published online April 15, 2025; DOI: https://doi.org/10.3350/cmh.2025.0379

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Metabolic health in antiviral era of chronic hepatitis B: Editorial on “Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues”: Shang-Chin Huang, Jia-Horng Kao; Clin Mol Hepatol 2026;32(1):423-425.
Published online April 11, 2025; DOI: https://doi.org/10.3350/cmh.2025.0369

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Advancing metabolic risk profiling in chronic hepatitis B: Reply to correspondence on “Metabolic health in antiviral era of chronic hepatitis B”
Shang-Chin Huang, Jia-Horng Kao
Clinical and Molecular Hepatology.2026; 32(1): e117. CrossRef
Correspondence to editorial 1 on “Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues”
Rui Huang, Mindie H. Nguyen
Clinical and Molecular Hepatology.2026; 32(1): e83. CrossRef
Steatosis Paradox: Unraveling Pathways of Suppressive Effect of Hepatic Steatosis on Hepatitis B Virus
Shang-Chin Huang, Jia-Horng Kao
Biomedical Journal.2026; : 100969. CrossRef

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Viral manipulation of host cell glutamine metabolism and glutamine rewiring in hepatic diseases: Editorial on “Glutamate dehydrogenase 1-dependent α-ketoglutarate promotes hepatitis B virus transcription by modulating histone methylations on the covalently closed circular DNA minichromosome”: Mehrangiz Dezhbord, Kyun-Hwan Kim; Clin Mol Hepatol 2026;32(1):385-389.
Published online April 11, 2025; DOI: https://doi.org/10.3350/cmh.2025.0366

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Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues: Rui Huang, Dae Won Jun, Hidenori Toyoda, Yao-Chun Hsu, Huy Trinh, Akito Nozaki, Toru Ishikawa, Tsunamasa Watanabe, Haruki Uojima, Daniel Q. Huang, Takashi Honda, Yasuhito Tanaka, Philip Vutien, Sebastián Marciano, Hiroshi Abe, Masaru Enomoto, Masanori Atsukawa, Hirokazu Takahashi, Kunihiko Tsuji, Koichi Takaguchi, Pei-Chien Tsai, Chia-Yen Dai, Jee-Fu Huang, Chung-Feng Huang, Ming-Lun Yeh, Eileen Yoon, Sung Eun Kim, Sang Bong Ahn, Gi-Ae Kim, Jang Han Jung, Soung Won Jeong, Hyunwoo Oh, Cheng-Hao Tseng, Masatoshi Ishigami, Angela Chau, Mayumi Maeda, Satoshi Yasuda, Makoto Chuma, Takanori Ito, Keigo Kawashima, Joanne Kimiko Liu, Adrian Gadano, Ritsuzo Kozuka, Norio Itokawa, Kaori Inoue, Tomonori Senoh, Jie Li, Wan-Long Chuang, Ramsey Cheung, Chao Wu, Ming-Lung Yu, Mindie H. Nguyen; Clin Mol Hepatol 2025;31(3):1003-1017.
Published online March 17, 2025; DOI: https://doi.org/10.3350/cmh.2024.1070

Background/Aims
Given the increase in prevalence of metabolic diseases, we investigated their long-term impacts on the outcomes of chronic hepatitis B (CHB) patients receiving nucleos(t)ide analogue (NA) treatment.
Methods
We analyzed data from CHB patients for whom initiated NA treatment from 30 centers. We balanced patient characteristics with and without metabolic disease (diabetes, obesity, dyslipidemia, and hypertension) via propensity-score matching (PSM) to evaluate adverse outcomes.
Results
The study included 4,500 patients. PSM yielded 909 pairs of patients with balanced characteristics. When stratified by the number of metabolic diseases, only patients with ≥2 metabolic diseases had an increased cumulative incidence of cirrhosis and overall death. However, when stratified by the presence of diabetes (regardless of the presence or number of other metabolic diseases), patients with diabetes (versus those without) had a significantly higher cumulative incidence of all outcomes: cirrhosis (P=0.009), hepatocellular carcinoma (HCC, P=0.023), and overall, liver-related, and non-liver-related death (P<0.001, P=0.026 and P<0.001, respectively). Having ≥2 metabolic diseases was associated with cirrhosis, overall death, and non-liver-related death but not HCC or liver-related death, while diabetes was significantly associated with a higher risk of all outcomes: cirrhosis (hazard ratio [HR]=3.75, P=0.004), HCC (HR=2.02, P=0.020), and overall, liver-related, and non-liver-related death (HR=2.53, P<0.001; HR=2.65, P=0.016; HR=2.38, P<0.001).
Conclusions
Having two or more metabolic diseases was associated with a higher risk of cirrhosis, overall death, and non-liver-related death, but having diabetes as a single metabolic disease was significantly associated with all adverse outcomes including cirrhosis, HCC, and overall, liver-related, and non-liver-related death.

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Jie Li, Liang Xu, Fajuan Rui, Sally Tran, Pei-Chien Tsai, Youwen Tan, Hidenori Toyoda, Qing-Lei Zeng, Huy Trinh, Yao-Chun Hsu, Tsunamasa Watanabe, Hiroshi Abe, Hiroyuki Motoyama, Yoko Yoshimaru, Takanori Suzuki, Taeang Arai, Masanori Atsukawa, Phillip Vut
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Regulation of hepatitis B virus cccDNA by metabolic pathways: Editorial on “GDH1-dependent α-ketoglutarate promotes HBV transcription by modulating histone methylations on the cccDNA minichromosome”: Hyeong-Jin Cho, Sung-Gyoo Park; Clin Mol Hepatol 2026;32(1):381-384.
Published online March 12, 2025; DOI: https://doi.org/10.3350/cmh.2025.0255

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Published online February 11, 2025; DOI: https://doi.org/10.3350/cmh.2025.0118

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Correspondence to editorial 1 on “Baveno VI-SSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis”
Haiyu Wang, Jinjun Chen
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Baveno VI-SSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis: Haiyu Wang, Weihao Liang, Ling Zhou, Jiankang Song, Biao Wen, Qiaoping Wu, Yuanjian Zhang, Xiaofeng Zhang, Haoran Ke, Yujun Tang, Fuyuan Zhou, Youfu Zhu, Weiqun Wen, Zhihua Liu, Yali Ji, Qintao Lai, Qinjun He, Wenfan Luo, Tingting Qi, Miaoxia Liu, Xiaoqin Lan, Yongpeng Chen, Ranran Xi, Junting Wan, Lin Dai, Yuan Li, Jinjun Chen; Clin Mol Hepatol 2025;31(3):866-880.
Published online February 5, 2025; DOI: https://doi.org/10.3350/cmh.2024.0609

Background/Aims
Cirrhotic patients with liver stiffness measurement (LSM) <20 kPa and platelet count ≥150×10⁹/L (Baveno VI criteria), otherwise spleen stiffness measurement (SSM) ≤40 kPa (Baveno VI-SSM criteria) can avoid endoscopy screening; however, no prospective data for their hepatic outcomes.
Methods
Compensated cirrhosis with HBV were prospectively enrolled from April 2019 to April 2022 and followed until July 2023. All patients underwent LSM, SSM and esophagogastroduodenoscopy assessment.
Results
Among 1,224 patients enrolled with median follow-up of 30 months (interquartile range, 21–42), the incidence of decompensation was greater in 560 patients with unfavored Baveno VI criteria (0.5 vs. 20.4 per 1,000 person-years, P=0.0004) than that in 664 patients with favored Baveno VI-SSM criteria. The Baveno VI-SSM model identified more patients (54.2%) as low-risk for decompensation than Baveno VII-SSM model (single cutoff) (48.4%, P=0.004) and than Baveno VI criteria (34.6%, P<0.0001) did. Patients with high-risk varices diagnosed via endoscopy following Baveno VI-SSM model assessment had greater probability of decompensation compared to those identified by the Baveno VII-SSM model (single cutoff) (42.8 vs. 21.1 per 1,000 person-years, P=0.0088). Additionally, among the 493 patients who underwent endoscopic re-assessment, 242 patients with favored Baveno VI-SSM criteria had much lower incidence of EV progression (2.6 vs. 99.5 per 1,000 person-years, P=0.0004) and lower risk of decompensation compared to 140 patients with unfavored Baveno VI-SSM model (0 vs. 34.2 per 1,000 person-years, P=0.0256).
Conclusions
Baveno VI-SSM model could identify HBV-related cirrhosis patients at low risk of decompensation, which was greatly improved upon Baveno VI-SSM reassessment.

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Correspondence to editorial 1 on “Baveno VI-SSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis”
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Haiyu Wang, Jinjun Chen
Clinical and Molecular Hepatology.2026; 32(1): e62. CrossRef
Correspondence to editorial 3 on “Baveno VI-SSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis”
Haiyu Wang, Jinjun Chen
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Mathias Jachs, Mattias Mandorfer
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JGH Open.2025;[Epub] CrossRef

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Viral hepatitis

Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0: Di Wu, Jia-Horng Kao, Teerha Piratvisuth, Xiaojing Wang, Patrick T.F. Kennedy, Motoyuki Otsuka, Sang Hoon Ahn, Yasuhito Tanaka, Guiqiang Wang, Zhenghong Yuan, Wenhui Li, Young-Suk Lim, Junqi Niu, Fengmin Lu, Wenhong Zhang, Zhiliang Gao, Apichat Kaewdech, Meifang Han, Weiming Yan, Hong Ren, Peng Hu, Sainan Shu, Paul Yien Kwo, Fu-sheng Wang, Man-Fung Yuen, Qin Ning; Clin Mol Hepatol 2025;31(Suppl):S134-S164.
Published online January 22, 2025; DOI: https://doi.org/10.3350/cmh.2024.0780

Abstract
PDF

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

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Correspondence to editorial on “Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial”
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Response to letters to editor "Next-Step Paradigms for Hepatitis B Functional Cure: Insights from the Anchor Combination Therapy Trial" and “Critical Appraisal of the Anchor RCT on Entecavir, Peginterferon Alfa-2b, and GM-CSF Combination Therapy”
Di Wu, Da Huang, Weiming Yan, Qin Ning
Hepatology International.2026;[Epub] CrossRef
Response to letter to editor—Machine learning prediction of rapid HBsAg seroclearance at week 24 in inactive carriers treated with pegylated interferon
Jianxia Dong, Sujun Zheng, Xinyue Chen
Hepatology International.2026;[Epub] CrossRef
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Liya Zhu, Fei Peng, Dingfang Pi, Jinzhi Lu
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Ruihan Gao, Shuting Liu, Shiyu Zhang, Xin Zhou, Bin Zhu, Baoju Wang
Annals of Hepatology.2026; : 102212. CrossRef
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Kui Wang, Ruchen Zhou
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Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial: Hyung Joon Yim, Yeon Seok Seo, Ji Hoon Kim, Won Kim, Young Kul Jung, Jae Young Jang, Sae Hwan Lee, Yun Soo Kim, Chang Wook Kim, Hyoung Su Kim, Jae-Jun Shim, Eun-Young Cho, In Hee Kim, Byung Seok Lee, Jeong-Hoon Lee, Byung Seok Kim, Jeong Won Jang, Hyun Woong Lee, Jung Hyun Kwon, Moon Young Kim, Do Seon Song, Jung Gil Park, Yoon Seok Lee, Eileen L. Yoon, Han Ah Lee, Seong Hee Kang, Jin Mo Yang; Clin Mol Hepatol 2025;31(3):810-822.
Published online January 17, 2025; DOI: https://doi.org/10.3350/cmh.2024.0819

Background/Aims
Besifovir (BSV) showed comparable antiviral activity and superior safety profiles to tenofovir disoproxil fumarate (TDF) in treatment-naïve chronic hepatitis B (CHB). However, no data are available regarding the antiviral efficacy and safety of BSV in patients with CHB who switched from long-term TDF to BSV. This study aimed to evaluate the outcome of a 48-week BSV therapy in patients with CHB who switched from long-term TDF treatment.
Methods
In this non-inferiority trial, 153 CHB patients treated with TDF for ≥48 weeks who had hepatitis B virus (HBV) DNA <20 IU/mL were randomized to receive either BSV 150 mg or TDF 300 mg for 48 weeks.
Results
The per-protocol analysis included 130 patients (BSV group, 64; TDF group, 66). The median duration of TDF use before enrollment was 4.14 years. After 48 weeks, 100.0% and 98.5% patients in the BSV and TDF groups, respectively, met the primary endpoint (HBV DNA <20 IU/mL), demonstrating the non-inferior antiviral efficacy of BSV to TDF (95% confidence interval –0.01 to 0.04; P>0.999), with a predefined margin of –0.18. The mean percentage changes in estimated glomerular filtration rates were slightly better in the BSV group (1.67±11.73%) than in the TDF group (–1.24±11.02%). The BSV group showed a significant improvement in bone turnover biomarkers compared to the TDF group; accordingly, hip and spine bone mineral density increased in the BSV group.
Conclusions
In patients with CHB receiving long-term TDF, switching to BSV may improve renal and bone safety with non-inferior antiviral efficacy compared to that of maintaining TDF.

Citations

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Correspondence to editorial on “Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial”
Hyung Joon Yim, Seong Hee Kang, Young Kul Jung, Jin Mo Yang
Clinical and Molecular Hepatology.2026; 32(1): e55. CrossRef
Besifovir: a viable option for long-term disease control in chronic hepatitis B: Editorial on “Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial”
Wai-Kay Seto
Clinical and Molecular Hepatology.2026; 32(1): 374. CrossRef
Tenofovir amibufenamide in chronic hepatitis B: Lipid changes and 144-week safety with tenofovir disoproxil fumarate-to-tenofovir amibufenamide switch
Zhi-Hao Zeng, Jin-Qing Liu, Min Zhang, Cai-Liang Qiu, Zhen-Yu Xu
World Journal of Gastroenterology.2025;[Epub] CrossRef

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High Steatosis-Associated Fibrosis Estimator scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic dysfunction-associated steatotic liver disease: Tung-Hung Su, Sheng-Shun Yang, Mei-Hsuan Lee, Wei-Yu Kao, Shang-Chin Huang, Fen-Fang Chen, Francis SK Poon, Lung-Wen Tsai, Yi-Ting Chen, Che Lin, Weichung Wang, W Ray Kim, Jia-Horng Kao; Clin Mol Hepatol 2025;31(3):796-809.
Published online January 6, 2025; DOI: https://doi.org/10.3350/cmh.2024.0822

Background/Aims
There are no hepatocellular carcinoma (HCC) surveillance recommendations for non-viral chronic liver diseases (CLD), such as metabolic dysfunction-associated steatotic liver disease (MASLD). We explored the Steatosis-Associated Fibrosis Estimator (SAFE) score to predict HCC in MASLD and other CLD etiologies.
Methods
Patients with various CLDs were included from medical centers in Taiwan. The SAFE score, consisting of age, body mass index, diabetes, and laboratory data, was calculated at baseline, and patients were traced for new development of HCC. The predictability of the SAFE score for HCC was analyzed using the sub-distribution hazard model with adjustments for competing risks.
Results
Among 12,963 CLD patients with a median follow-up of 4 years, 258 developed HCC. The SAFE score classifies 1-, 3-, and 5-year HCC risk regardless of CLD etiologies. High (≥100) and intermediate (0–100) SAFE scores increased 11 and 2 folds HCC risks compared to low (<0) SAFE scores. Combining two lower risk tiers (SAFE<100), a high SAFE score (≥100) was associated with a 7.5-fold risk of HCC (adjusted sub-distributional hazard ratio [aSHR] 7.54; 95% confidence interval (CI) 5.38–10.60). A high SAFE score increased the risks of HCC in subgroups of viral hepatitis, non-viral hepatitis (aSHR 11.10; 95% CI 3.97–31.30) and MASLD (aSHR 4.23; 95% CI 1.43–12.50). A hospital cohort (n=8,103) and a community MASLD cohort (n=120,166) validated the high SAFE score (≥100) for HCC risk prediction.
Conclusions
The SAFE score stratifies high risks for HCC in CLD patients regardless of etiologies and helps to select at-risk candidates for HCC surveillance.

Citations

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HCC predictors in routine practice for patients with chronic liver diseases: Correspondence to editorial on “High SAFE scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic dysfunction associated steatotic liver disease”
Tung-Hung Su, Jia-Horng Kao
Clinical and Molecular Hepatology.2026; 32(1): e52. CrossRef
Can SAFE score be utilized as a universal hepatocellular carcinoma prediction score?: Editorial on “High Steatosis-Associated Fibrosis Estimator scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic dysfunction-associated
Michael Kwan-Lung Ko, Loey Lung-Yi Mak
Clinical and Molecular Hepatology.2026; 32(1): 371. CrossRef
Risk stratification for hepatocellular carcinoma in metabolic dysfunction-associated steatotic liver disease: Editorial on “High Steatosis-Associated Fibrosis Estimator scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic
Ho Soo Chun, Minjong Lee
Clinical and Molecular Hepatology.2026; 32(1): 368. CrossRef
Editorial: Residual HCC Risk After Hepatitis C Cure—Can Polygenic Risk Scores Refine Surveillance?
Heechul Nam, Sung Won Lee
Alimentary Pharmacology & Therapeutics.2026; 63(10): 1427. CrossRef
Absence of steatosis combined with cardiometabolic risk factors confers the highest hepatocellular carcinoma risk in treated chronic hepatitis B
Hung-Wei Wang, Hsueh-Chou Lai, Wei-Fan Hsu, Sheng-Hung Chen, Yi-Chun Kuo, Cheng-Yuan Peng
Annals of Medicine.2026;[Epub] CrossRef

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5 Web of Science
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Viral hepatitis

Expanding treatment eligibility for chronic hepatitis B: Balancing benefits, limitations, and healthcare access: Correspondence to editorial on “Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TORCH-B trial”: Yao-Chun Hsu, Chi-Yi Chen, Jaw-Town Lin; Clin Mol Hepatol 2025;31(2):e169-e172.
Published online December 23, 2024; DOI: https://doi.org/10.3350/cmh.2024.1138

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6,346 View
34 Download

Viral hepatitis

Global inequality in the burden of hepatitis B from 1990 to 2021: Findings from the global burden of disease study 2021: Letter to the editor on “Comprehensive approach to controlling chronic hepatitis B in China”: Chunlong Liu, Jiangtao Yu; Clin Mol Hepatol 2025;31(2):e134-e136.
Published online December 17, 2024; DOI: https://doi.org/10.3350/cmh.2024.1085

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The burden of Parkinson’s disease, 1990–2021: a systematic analysis of the Global Burden of Disease study 2021
Xi-Chen Wu, Yi-Yue Dong, Yu-Chen Ying, Guang-Yan Chen, Qian Fan, Ping Yin, Yue-Lai Chen
Frontiers in Aging Neuroscience.2025;[Epub] CrossRef

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Viral hepatitis

Reconsidering treatment indications for chronic hepatitis B: Insights from the TORCH-B roll-over study: Editorial on “Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TORCH-B trial”: Chih-Wen Wang, Ming-Lung Yu; Clin Mol Hepatol 2025;31(2):606-609.
Published online December 3, 2024; DOI: https://doi.org/10.3350/cmh.2024.1078

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Expanding treatment eligibility for chronic hepatitis B: Balancing benefits, limitations, and healthcare access: Correspondence to editorial on “Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TOR
Yao-Chun Hsu, Chi-Yi Chen, Jaw-Town Lin
Clinical and Molecular Hepatology.2025; 31(2): e169. CrossRef

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Viral hepatitis

Treatment response to nucleos(t)ide analogs in chronic hepatitis B with mildly elevated alanine aminotransferase: Letter to the editor on “Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TORCH-B trial”: Jian Wang, Fei Cao, Chuanwu Zhu, Chao Wu, Rui Huang; Clin Mol Hepatol 2025;31(2):e140-e142.
Published online December 3, 2024; DOI: https://doi.org/10.3350/cmh.2024.0960

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Expanding treatment eligibility for chronic hepatitis B: Balancing benefits, limitations, and healthcare access: Correspondence to editorial on “Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TOR
Yao-Chun Hsu, Chi-Yi Chen, Jaw-Town Lin
Clinical and Molecular Hepatology.2025; 31(2): e169. CrossRef

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37 Download
1 Web of Science
Crossref

Viral hepatitis

Mechanisms of hepatocellular carcinoma and cirrhosis development in concurrent steatotic liver disease and chronic hepatitis B: Saisai Zhang, Lung-Yi Mak, Man-Fung Yuen, Wai-Kay Seto; Clin Mol Hepatol 2025;31(Suppl):S182-S195.
Published online November 21, 2024; DOI: https://doi.org/10.3350/cmh.2024.0837

Abstract
PDF

Chronic hepatitis B (CHB) poses a major global public health challenge and is a leading cause of cirrhosis and liver cancer. Hepatic steatosis is common in individuals with CHB compared to the non-CHB population and is particularly prevalent in hepatitis B virus (HBV)-endemic regions, affecting about one-third of CHB patients. The interaction between hepatic steatosis and CHB-related disease progression is complex and still under debate. Evidence demonstrates that co-existing steatosis may worsen liver fibrosis while paradoxically increasing the likelihood of achieving better HBV control. In particular, despite the association of steatotic liver disease (SLD) with lower HBV viral loads and higher rates of HBsAg seroclearance, the coexistence of CHB and SLD can potentially accelerate liver disease progression. Factors such as fat deposition, lipotoxicity, oxidative stress, and chronic inflammation in SLD may foster a pro-fibrotic and pro-carcinogenic environment, accelerating the disease progression. Additionally, loss of global DNA methylation, changes in the immune microenvironment, and genetic susceptibility further contribute to the development of CHB-related cirrhosis and hepatocellular carcinoma (HCC). This review examines the mechanisms driving liver disease progression and the heightened risk of cirrhosis and HCC in patients with concurrent CHB and steatotic liver disease, underscoring the importance of prioritizing antiviral therapy for CHB in addition to addressing SLD.

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Viral hepatitis

Prospect of emerging treatments for hepatitis B virus functional cure: Rex Wan-Hin Hui, Lung-Yi Mak, James Fung, Wai-Kay Seto, Man-Fung Yuen; Clin Mol Hepatol 2025;31(Suppl):S165-181.
Published online November 14, 2024; DOI: https://doi.org/10.3350/cmh.2024.0855

Abstract
PDF

Functional cure, defined as sustained hepatitis B surface antigen (HBsAg) seroclearance with unquantifiable hepatitis B virus (HBV) DNA at 24 weeks off treatment, is a favorable treatment endpoint in chronic hepatitis B (CHB). Nonetheless, functional cure is rarely attained with the current treatment modalities of nucleos(t)ide analogues (NUCs) and pegylated interferon alpha. Multiple novel virus-targeting agents and immunomodulators are under development for HBV with functional cure as the treatment goal. Among virus-targeting agents, antisense oligonucleotides and small-interfering RNAs are the most advanced in the developmental pipeline, and can induce potent and sustainable HBsAg suppression. The other virus-targeting agents have varying effects on HBsAg and HBV DNA, depending on the drug mechanism. In contrast, immunomodulators have modest effects on HBsAg and have limited roles in monotherapy. Multiple combination regimens incorporating RNA interference agents with immunomodulators have been studied through many ongoing clinical trials. These combination strategies demonstrate synergistic effects in inducing functional cure, and will likely be the future direction of development. Despite the promising results, research is warranted to optimize treatment protocols and to establish criteria for NUC withdrawal after novel therapies. Functional cure is now an attainable target in CHB, and the emerging novel therapeutics will revolutionize CHB management.

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Karen Cheuk-Ying Ho, Rex Wan-Hin Hui, Wai-Kay Seto, Man-Fung Yuen, Lung-Yi Mak
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Viral hepatitis

Reply to correspondence on “Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using vibration-controlled transient elastography: Systematic review and meta-analysis”: Mirko Zoncapè, Emmanuel A. Tsochatzis; Clin Mol Hepatol 2025;31(1):e117-e118.
Published online November 11, 2024; DOI: https://doi.org/10.3350/cmh.2024.0994

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5,568 View
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Viral hepatitis

Correspondence to letter to the editor on “Contemporary awareness of viral hepatitis between 2012 and 2022 among Korean adults”: Chang Hun Lee, In Hee Kim, Sook-Hyang Jeong; Clin Mol Hepatol 2025;31(2):e149-e151.
Published online November 6, 2024; DOI: https://doi.org/10.3350/cmh.2024.0944

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Viral hepatitis

Momentum towards simplifying and expanding treatment for chronic hepatitis B: The body of evidence continues to grow: Editorial on “Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TORCH-B trial”: Robert J. Wong; Clin Mol Hepatol 2025;31(2):603-605.
Published online October 29, 2024; DOI: https://doi.org/10.3350/cmh.2024.0929

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Expanding treatment eligibility for chronic hepatitis B: Balancing benefits, limitations, and healthcare access: Correspondence to editorial on “Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TOR
Yao-Chun Hsu, Chi-Yi Chen, Jaw-Town Lin
Clinical and Molecular Hepatology.2025; 31(2): e169. CrossRef

6,325 View
35 Download
1 Web of Science
Crossref

Hepatic neoplasm

Correspondence to editorial on “Genetically-modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcinoma lesions in a clinical setting”: Shunda Du, Karin Wisskirchen, Ke Zhang, Ulrike Protzer; Clin Mol Hepatol 2025;31(1):e44-e47.
Published online October 21, 2024; DOI: https://doi.org/10.3350/cmh.2024.0781

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Reply to correspondence on “Genetically-modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcinoma lesions in a clinical setting”
Antonio Bertoletti, Anthony T Tan
Clinical and Molecular Hepatology.2025; 31(1): e113. CrossRef

5,082 View
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Viral hepatitis

Chronic hepatitis B, extrahepatic malignancies and the use of antiviral drugs: Meng-Che Wu, Shih-Chi Yang, Shuo-Yan Gau; Clin Mol Hepatol 2025;31(1):e19-e20.
Published online October 17, 2024; DOI: https://doi.org/10.3350/cmh.2024.0906

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Viral hepatitis

Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TORCH-B trial: Yao-Chun Hsu, Chi-Yi Chen, Cheng-Hao Tseng, Chieh-Chang Chen, Teng-Yu Lee, Ming-Jong Bair, Jyh-Jou Chen, Yen-Tsung Huang, I-Wei Chang, Chi-Yang Chang, Chun-Ying Wu, Ming-Shiang Wu, Lein-Ray Mo, Jaw-Town Lin; Clin Mol Hepatol 2025;31(1):213-226.
Published online October 17, 2024; DOI: https://doi.org/10.3350/cmh.2024.0640

Background/Aims
Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population.
Methods
This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019).
Results
Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg.
Conclusions
In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

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Hepatic neoplasm

Reply to correspondence on “Genetically-modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcinoma lesions in a clinical setting”: Antonio Bertoletti, Anthony T Tan; Clin Mol Hepatol 2025;31(1):e113-e116.
Published online October 11, 2024; DOI: https://doi.org/10.3350/cmh.2024.0867

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Viral hepatitis

Contemporary awareness of viral hepatitis between 2012 and 2022 among Korean adults: Donghee Kim, Won Kim, Aijaz Ahmed; Clin Mol Hepatol 2025;31(1):e5-e7.
Published online October 8, 2024; DOI: https://doi.org/10.3350/cmh.2024.0849

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Correspondence to letter to the editor on “Contemporary awareness of viral hepatitis between 2012 and 2022 among Korean adults”
Chang Hun Lee, In Hee Kim, Sook-Hyang Jeong
Clinical and Molecular Hepatology.2025; 31(2): e149. CrossRef

7,335 View
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Viral hepatitis

Correspondence to editorial on “Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using vibration-controlled transient elastography: Systematic review and meta-analysis”: Young-Joo Jin, Seung Up Kim; Clin Mol Hepatol 2025;31(1):e55-e57.
Published online October 7, 2024; DOI: https://doi.org/10.3350/cmh.2024.0846

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Reply to correspondence on “Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using vibration-controlled transient elastography: Systematic review and meta-analysis”
Mirko Zoncapè, Emmanuel A. Tsochatzis
Clinical and Molecular Hepatology.2025; 31(1): e117. CrossRef

5,692 View
32 Download
1 Web of Science
Crossref

Viral hepatitis

The use of transient elastography for predicting hepatocellular carcinoma in chronic hepatitis B patients: Editorial on “Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using vibration-controlled transient elastography: Systematic review and meta-analysis”: Mirko Zoncapè, Emmanuel A. Tsochatzis; Clin Mol Hepatol 2025;31(1):268-274.
Published online September 24, 2024; DOI: https://doi.org/10.3350/cmh.2024.0817

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Citations to this article as recorded by

Reply to correspondence on “Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using vibration-controlled transient elastography: Systematic review and meta-analysis”
Mirko Zoncapè, Emmanuel A. Tsochatzis
Clinical and Molecular Hepatology.2025; 31(1): e117. CrossRef
Correspondence to editorial on “Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using vibration-controlled transient elastography: Systematic review and meta-analysis”
Young-Joo Jin, Seung Up Kim
Clinical and Molecular Hepatology.2025; 31(1): e55. CrossRef
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Mi Na Kim, Geun U. Park, Seng Chan You, Jae Seung Lee, Hye Won Lee, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn
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Viral hepatitis

Correspondence

Viral hepatitis

Viral hepatitis

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