Clinical and Molecular Hepatology

TLR7 agonist plus anti-PD-L1 enhances HBsAg decline and reinvigorates HBV-specific CD8+ T cells: OCEANcure05 RCT study: Yuying Chen, Ting Wu, Da Huang, Zhize Yuan, Ruiqi Zhai, Bingyao He, Wenyu Wu, Wei Yuan, Peng Wang, Zhongnan Xu, Shuna Wang, Dandan Huo, Meifang Han, Weiming Yan, Di Wu, Qin Ning; Received April 29, 2026 Accepted September 20, 2026 Published online September 29, 2026; DOI: https://doi.org/10.3350/cmh.2026.0476 [Accepted]

Abstract
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Background & Aims
TQ-A3334, a selective Toll-like receptor 7 (TLR7) agonist, activates innate immunity against hepatitis B virus (HBV). TQ-B2450, a humanized programmed death ligand 1 (PD-L1) antibody, could restore T cell function. This study assessed the safety, efficacy, and immunological profile of nucleos(t)ide analogues (NAs) plus TQ-A3334 with or without TQ-B2450 in virally suppressed patients with chronic hepatitis B (CHB).
Methods
In the OCEANcure05 study (NCT04202653), 24 NAs-experienced patients with hepatitis B surface antigen (HBsAg) 250–5000 IU/mL were randomized to NAs monotherapy, dual therapy (NAs + TQ-A3334), or triple therapy (NAs + TQ-A3334 + TQ-B2450) for 24 weeks. The primary endpoint was HBsAg reduction at end of treatment (EOT). Single-cell RNA-seq and flow cytometry were conducted to characterize HBV-specific CD8⁺ T cell responses.
Results
Triple therapy demonstrated numerically greater HBsAg reduction at EOT than dual therapy or monotherapy. Parallel trends were observed for HBV RNA and hepatitis B e antigen levels. In the triple therapy arm, baseline PD-L1 expression declined more markedly in patients with HBsAg decline ≥0.5 log₁₀ IU/mL. Triple therapy increased IFN-γ, TNF-α, and CD107a expression in HBV-specific CD8⁺ T cells and broadened HBV peptide recognition. Reversible thyroid abnormalities were the predominant adverse event during triple therapy. No serious adverse events or deaths occurred.
Conclusions
The combination therapy showed acceptable tolerability. In virally suppressed patients, the addition of PD-L1 antibody to NAs plus TLR7 agonist induced moderate HBsAg decline and elicited HBV-specific CD8⁺ T cell responses, supporting multi-target immunotherapy as a potential treatment strategy for CHB.

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RNAi-mediated HBV antigen shutdown enhances the antiviral immune effects of PEGIFNα via T and B cell crosstalk remodeling: Wenjing Zai, Kongying Hu, Mengying He, Ziyang Song, Pan Gao, Chen Luo, Minxiang Xie, Asha Ashuo, Min Yang, Jieliang Chen, Zhenghong Yuan; Received April 17, 2026 Accepted September 3, 2026 Published online September 11, 2026; DOI: https://doi.org/10.3350/cmh.2026.0385 [Accepted]

Abstract
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Backgrounds/Aims
PEGylated interferon-α (PEGIFNα) shows promise in treating chronic hepatitis B (CHB), yet patient response remains suboptimal. While suppressing hepatitis B virus (HBV) antigens by RNA interference (RNAi) could enhance PEGIFNα efficacy in CHB patients, the underlying immunological mechanisms remain obscure.
Methods
Using our newly established extracellular humanized IFNAR (IFNAR-hEC) mouse model of chronic HBV infection, we evaluated the efficacy of a GalNac-conjugated siRNA (GalNac-siHBV) alone or in combination with PEGIFNα. Phenotypic and functional characteristics of immune cells were assessed by flow cytometry, ELISpot, and single-cell RNA sequencing (scRNA-seq).
Results
High circulating HBsAg reduced antiviral effects and immune responsiveness of PEGIFNα. Combined PEGIFNα and RNAi therapy synergistically and durably suppressed HBsAg (~4log10 IU/mL, vs PBS) and achieved HBsAg seroconversion in ~30% of mice, outperforming either monotherapy. Mechanistically, PEGIFNα enhanced global T and B cell function, whereas combined therapy further amplified HBV-specific T and B cell responses. scRNA-seq analysis indicated that combined therapy attenuated inhibitory B cell-B cell interactions, strengthened MHC-I-mediated T cell crosstalk, and enhanced MHC-II signaling networks across B cells and hepatocytes/Cd8+ T cells, collectively improving the lymphocyte functionality and facilitating HBsAg seroconversion. Reinforcing MHC-I/II signaling with agonistic antibodies (α4-1BB, αCD40) or IL-2-Fc further potentiated antiviral immune responses of combinational regimen.
Conclusions
Combined RNAi and PEGIFNα therapy exerts synergistic antiviral effects by relieving HBV antigen-induced immune tolerance and orchestrating a functional T cell-B cell crosstalk network centered on MHC-I/II signaling. Enhancing antigen presentation pathways represents a promising adjunctive strategy to improve functional cure rate of CHB.

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Viral load rather than transaminase: an international perspective on the KASL–EALA 2026 guideline for chronic hepatitis B: Tatsuya Kanto, Fabien Zoulim, Ming-Lung Yu; Received July 17, 2026 Accepted July 18, 2026 Published online August 5, 2026; DOI: https://doi.org/10.3350/cmh.2026.0908 [Accepted]

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Comparison of clinical practice guidelines for chronic hepatitis B: natural history classification and treatment initiation: Gi-Ae Kim, Won-Mook Choi, Gwang Hyeon Choi, In Hee Kim, Tatsuya Kanto, Ming-Lung Yu, Young-Suk Lim; Clin Mol Hepatol 2026;32(3):1186-1200.
Published online June 29, 2026; DOI: https://doi.org/10.3350/cmh.2026.0697

Abstract
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International and regional clinical practice guidelines (CPGs) for chronic hepatitis B (CHB) have recently been updated to incorporate evolving clinical evidence. This review compares the latest major CPGs regarding natural history classification, treatment initiation, and selection of antiviral agents, specifically focusing on updates from the Korean Association for the Study of the Liver-East Asia Liver Alliance (KASL-EALA), the American Association for the Study of Liver Diseases (AASLD), the European Association for the Study of the Liver (EASL), and the World Health Organization (WHO). While all guidelines recognize the heterogeneous and dynamic nature of CHB, managing patients in the “grey zone” or indeterminate phase remains a major challenge. The KASL–EALA 2026 guideline introduces a novel framework based primarily on hepatitis B virus (HBV) DNA levels—independent of alanine aminotransferase criteria—eliminating the indeterminate category to better align with hepatocellular carcinoma risks and simplify treatment decision-making. In contrast, AASLD 2025, EASL 2025, and WHO 2024 retain conventional immunological phase-based classifications for natural history. For treatment indications, all four guidelines advocate broader access to antiviral therapy despite their divergent structural approaches. AASLD suggests shared decision-making, EASL emphasizes individualized risk assessment, and WHO 2024 abandons the phase-based framework for treatment decisions entirely. Understanding these key similarities and differences will help clinicians optimize patient care and inform future efforts toward global harmonization in CHB management.

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Integrated network pharmacology and single-cell analysis identify CDK4 and LGALS1 as potential targets for a modified Chaihu Shugan San formula in hepatocellular carcinoma
Youmen Zhou, Yahui Li, Wei Shi, Pengshuo Yang, Fei Li
Letters in Drug Design & Discovery.2026; 23(8): 100565. CrossRef
Expanding treatment guidelines for chronic hepatitis B: A narrative review
Chih-Lin Lin, Jia-Horng Kao
Journal of the Formosan Medical Association.2026;[Epub] CrossRef

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Chronic viral hepatitis with concurrent metabolic dysfunction-associated steatotic liver disease: dual etiology challenges: Shang-Chin Huang, Yi-Fen Shih, Chun-Jen Liu; Clin Mol Hepatol 2026;32(Suppl):e2026.0387.
Published online June 25, 2026; DOI: https://doi.org/10.3350/cmh.2026.0387

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The overlapping epidemics of chronic viral hepatitis and metabolic dysfunction-associated steatotic liver disease (MASLD) present a complex challenge in modern hepatology. In chronic hepatitis B, a unique “steatosis paradox” emerges: while isolated hepatic steatosis provides a suppressive microenvironment that promotes hepatitis B viral clearance, the concomitant systemic cardiometabolic burden acts dose-dependently to drive fibrogenesis and hepatocellular carcinoma (HCC). Conversely, chronic hepatitis C and host metabolic dysfunctions exhibit synergistic destruction. Hepatitis C virus actively hijacks lipid metabolism and induces insulin resistance. Even after viral eradication via direct-acting antivirals, residual steatosis and glycemic abnormalities remain formidable drivers of HCC. Consequently, the traditional virocentric paradigm is no longer sufficient. Clinical management should pivot toward precision risk stratification and a multidisciplinary dual-target approach, equally prioritizing sustained viral suppression and aggressive metabolic remission. This review summarizes the divergent virus-MASLD interactions, optimal clinical strategies, current challenges and future opportunities.

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Steatotic liver disease spectrum: From MASLD to MetALD and beyond - Clinical outcomes and precision medicine frontiers
Won Kim
Clinical and Molecular Hepatology.2026; 32(Suppl): e2026.1072. CrossRef

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KASL clinical practice guidelines for management of chronic hepatitis B Endorsed by the East Asia Liver Alliance (EALA): Won-Mook Choi, Ji Won Han, Tae Hyung Kim, Miyoung Choi, Moon Haeng Hur, Hyo Young Lee, Han Ah Lee, Byeong Geun Song, Heechul Nam, Jeong-Ju Yoo, Chang Hun Lee, Gi-Ae Kim, Hye Won Lee, Gwang Hyeon Choi, Young Eun Chon, Yun Bin Lee, Dong Hyun Sinn, Bo Hyun Kim, In Hee Kim, on behalf of the Korean Association for the Study of the Liver (KASL); Clin Mol Hepatol 2026;32(3):1029-1116.
Published online June 12, 2026; DOI: https://doi.org/10.3350/cmh.2026.0579

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Comparison of clinical practice guidelines for chronic hepatitis B: natural history classification and treatment initiation
Gi-Ae Kim, Won-Mook Choi, Gwang Hyeon Choi, In Hee Kim, Tatsuya Kanto, Ming-Lung Yu, Young-Suk Lim
Clinical and Molecular Hepatology.2026; 32(3): 1186. CrossRef
Precision switching from entecavir to tenofovir alafenamide in chronic hepatitis B: a narrative review of matching the patient phenotype to efficacy, safety, and value
Soon Woo Nam
Journal of Yeungnam Medical Science.2026; 43: 55. CrossRef
2026 Korean Association for the Study of the Liver Guidelines for Chronic Hepatitis B Management: A Radiological Perspective
Hyo Jung Park, So Yeon Kim, Bo Hyun Kim
Korean Journal of Radiology.2026; 27(10): 925. CrossRef

9,639 View
391 Download
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Depression and suicide-related events associated with tenofovir use in chronic hepatitis B: A pharmacovigilance analysis: You Deng, Wenya Chen, Weina Lu, Chao Sun, Wen Xie; Clin Mol Hepatol 2026;32(3):e320-e325.
Published online March 25, 2026; DOI: https://doi.org/10.3350/cmh.2026.0210

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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; Clin Mol Hepatol 2026;32(3):1117-1134.
Published online March 18, 2026; DOI: https://doi.org/10.3350/cmh.2026.0177

Hepatitis B flare is a common complication of chronic hepatitis B and is defined as an increase in HBV viral load associated with abnormal alanine aminotransferases (ALT), the consensus being an ALT level ≥5 times the upper 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 associated mortality, potentially requiring liver transplantation. Initial assessment should exclude other causes of liver dysfunction and determine severity and prognosis. General prognostic models of ACLF are useful but the COSSH-ACLF II score is specific to HBV. Early initiation of nucleos(t)ide analogues is crucial, even in severe HBV flares; it can reduce mortality by 73.6%. Once jaundice and coagulopathy occur, salvage by antivirals is challenging, and liver transplantation should be considered. However, many patients may not be suitable candidates for transplant or donor livers may not be available, as is common in Asia. Recently, there has been increasing evidence of the benefits of adjunctive therapies such as corticosteroids and plasma exchange, but there are associated risks and these approaches should be considered rescue therapies in severe HBV flares or ACLF. Liver transplant is the ultimate intervention when these other strategies fail. In summary, HBV flares are clinically serious events that can lead to hepatic decompensation, ACLF, and the need for a donor liver; however, strategies for rescue should be considered before liver transplantation.

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Capturing systemic disease burden in MASLD: Toward integrated liver–kidney–cardiovascular economic models: Reply to correspondence on “Evaluating treatment response thresholds for cost-effective treatment in metabolic dysfunction-associated steatotic liver disease”: Anna Di Sessa, Gianmario Forcina, Emanuele Miraglia del Giudice; Clin Mol Hepatol 2026;32(3):e447-e449.
Published online February 11, 2026; DOI: https://doi.org/10.3350/cmh.2026.0160

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Incorporating chronic kidney disease into the cost-effectiveness of MASLD treatment: Correspondence to letter to the editor on “Evaluating treatment response thresholds for cost-effective treatment in metabolic dysfunction-associated steatotic liver disease”: Eileen L. Yoon, Jeong-Yeon Cho, Mimi Kim, Huiyul Park, Hye-Lin Kim, Dae Won Jun; Clin Mol Hepatol 2026;32(3):e415-e418.
Published online February 2, 2026; DOI: https://doi.org/10.3350/cmh.2026.0099

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Capturing systemic disease burden in MASLD: Toward integrated liver–kidney–cardiovascular economic models: Reply to correspondence on “Evaluating treatment response thresholds for cost-effective treatment in metabolic dysfunction-associated steatotic live
Anna Di Sessa, Gianmario Forcina, Emanuele Miraglia del Giudice
Clinical and Molecular Hepatology.2026; 32(3): e447. CrossRef

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Correspondence to letter to the editor on “Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0”: Di Wu, Xiaojing Wang, Weiming Yan, Man-Fung Yuen, Qin Ning; Clin Mol Hepatol 2026;32(3):e408-e410.
Published online January 27, 2026; DOI: https://doi.org/10.3350/cmh.2026.0031

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From immune reshaping to functional cure: Translational considerations for natural killer cell therapy in hepatitis B virus: Letter to the editor on “Dissecting antibody-mediated natural killer cell effects reveals a cytotoxic CX3CR1⁺KLRC2^-CD16^hi subset linked to hepatitis B virus outcomes”: Long Xu, Yan Wang, Guiqiang Wang; Clin Mol Hepatol 2026;32(3):e312-e314.
Published online January 14, 2026; DOI: https://doi.org/10.3350/cmh.2025.1463

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Correspondence to letter to the editor on “Dissecting antibody-mediated natural killer cell effects reveals a cytotoxic CX3CR1+KLRC2-CD16hi subset linked to hepatitis B virus outcomes”
Zihan Jin, Libo Tang, Yuhao Wang, Shihong Zhong, Yongyin Li
Clinical and Molecular Hepatology.2026; 32(3): e427. CrossRef

1,281 View
59 Download
1 Web of Science
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Letter to the editor on “Evaluating treatment response thresholds for cost-effective treatment in metabolic dysfunction-associated steatotic liver disease”: Anna Di Sessa, Gianmario Forcina, Emanuele Miraglia del Giudice; Clin Mol Hepatol 2026;32(3):e291-e293.
Published online January 9, 2026; DOI: https://doi.org/10.3350/cmh.2025.1417

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Incorporating chronic kidney disease into the cost-effectiveness of MASLD treatment: Correspondence to letter to the editor on “Evaluating treatment response thresholds for cost-effective treatment in metabolic dysfunction-associated steatotic liver disea
Eileen L. Yoon, Jeong-Yeon Cho, Mimi Kim, Huiyul Park, Hye-Lin Kim, Dae Won Jun
Clinical and Molecular Hepatology.2026; 32(3): e415. CrossRef
Capturing systemic disease burden in MASLD: Toward integrated liver–kidney–cardiovascular economic models: Reply to correspondence on “Evaluating treatment response thresholds for cost-effective treatment in metabolic dysfunction-associated steatotic live
Anna Di Sessa, Gianmario Forcina, Emanuele Miraglia del Giudice
Clinical and Molecular Hepatology.2026; 32(3): e447. CrossRef

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2 Web of Science
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Comment on the expert consensus on treatment approaches for achieving functional cure in chronic hepatitis B: Letter to the editor on “Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0”: Seng-Gee Lim, Melanie Paff; Clin Mol Hepatol 2026;32(3):e285-e287.
Published online December 26, 2025; DOI: https://doi.org/10.3350/cmh.2025.1441

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Correspondence to letter to the editor on “Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0”
Di Wu, Xiaojing Wang, Weiming Yan, Man-Fung Yuen, Qin Ning
Clinical and Molecular Hepatology.2026; 32(3): e408. CrossRef

1,925 View
96 Download
1 Web of Science
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Correspondence to editorial on “Predictive machine learning model in intensive care unit patients with acute-on-chronic liver failure and two or more organ failures”: Mengyi Zhang, Yee Hui Yeo, Jian Zu, Jonel Trebicka, Fanpu Ji; Clin Mol Hepatol 2026;32(3):e346-e348.
Published online November 11, 2025; DOI: https://doi.org/10.3350/cmh.2025.1218

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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

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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
New insights into antibody-mediated NK cell immunity in hepatitis B: Editorial on “Dissecting antibody-mediated NK cell effects reveals a cytotoxic CX3CR1⁺KLRC2⁻CD16hi subset linked to HBV outcomes”
Zuzana Macek Jilkova, Caroline Aspord
Clinical and Molecular Hepatology.2026; 32(3): 1448. CrossRef
Correspondence to editorial on “Dissecting antibody-mediated natural killer cell effects reveals a cytotoxic CX3CR1+KLRC2CD16hi subset linked to hepatitis B virus outcomes”
Libo Tang, Yuhao Wang, Zihan Jin, Shihong Zhong, Yongyin Li
Clinical and Molecular Hepatology.2026; 32(3): e384. CrossRef
Stimulation of the Stimulator of Interferon Genes Pathway Leads to Inhibition of Hepatitis B Virus Replication: Insights Into the Role of Hepatic Macrophages
Mingyuan Zhang, Xiaomei Wang, Hongqin Xu, Hao Meng, Jie Zhou, Xiaoyu Wen, Yingyu Zhang, Jinglan Jin, Qinlong Jin, Guan Huei Lee, Yanhang Gao, Junqi Niu
The Journal of Infectious Diseases.2026;[Epub] CrossRef
Sequential combination of anti-PD-1 antibody and PEG-IFNα in chronic hepatitis B patients: correlates of HBsAg loss with enhanced T-cell responses
Hongmin Wang, Chao Zhang, Xiaoying Li, Yaping Li, Xin Zhang, Ruonan Xu, Kaili Wang, Sa Lv, Xing Fan, Qing Wang, Shanquan Liu, Shengxian Yang, Xiaoning Zhang, Shuangsuo Dang, Fu-Sheng Wang, Junliang Fu
Emerging Microbes & Infections.2026;[Epub] CrossRef
Research Progress on Mechanisms of Immune Tolerance Induced by Hepatitis B Surface Antigen in Chronic HBV Infection
Li Wang
Journal of Immunology Research.2026;[Epub] CrossRef

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Harmonized ACLF prognostication with explainable machine learning models: Traversing from counts to composition: Editorial on “Predictive machine learning model in intensive care unit patients with acute-on-chronic liver failure and two or more organ failures”: Sagnik Biswas, Akash Roy; Clin Mol Hepatol 2026;32(3):1386-1389.
Published online October 20, 2025; DOI: https://doi.org/10.3350/cmh.2025.1154

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Correspondence to editorial on “Predictive machine learning model in intensive care unit patients with acute-on-chronic liver failure and two or more organ failures”
Mengyi Zhang, Yee Hui Yeo, Jian Zu, Jonel Trebicka, Fanpu Ji
Clinical and Molecular Hepatology.2026; 32(3): e346. CrossRef

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42 Download
1 Web of Science
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Correspondence to editorial on “Human cytomegalovirus reactivation in cirrhosis patients with acute decompensation”: Changze Hong, Jinjun Chen; Clin Mol Hepatol 2026;32(3):e336-e338.
Published online September 29, 2025; DOI: https://doi.org/10.3350/cmh.2025.1063

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Rethinking ACLF prognosis: Can machine learning outperform conventional scores?: Editorial on “Predictive machine learning model in intensive care unit patients with acute-on-chronic liver failure and two or more organ failures”: Jung Hee Kim; Clin Mol Hepatol 2026;32(3):1383-1385.
Published online September 23, 2025; DOI: https://doi.org/10.3350/cmh.2025.1053

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Correspondence to editorial on “Predictive machine learning model in intensive care unit patients with acute-on-chronic liver failure and two or more organ failures”
Mengyi Zhang, Yee Hui Yeo, Jian Zu, Jonel Trebicka, Fanpu Ji
Clinical and Molecular Hepatology.2026; 32(3): e346. CrossRef

2,105 View
87 Download
1 Web of Science
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Clarifying residual drug effects and subgroup outcomes in TDF-to-BSV switch trials: Letter to the editor on “Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial”: Lihuang Su, Tongtong Pan; Clin Mol Hepatol 2026;32(3):e274-e275.
Published online September 23, 2025; DOI: https://doi.org/10.3350/cmh.2025.1034

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Human cytomegalovirus reactivation in decompensated cirrhosis: marker of immunosuppression or contributor to severity?: Editorial on “Human cytomegalovirus reactivation in cirrhosis patients with acute decompensation”: Zhujun Cao, Richard Moreau; Clin Mol Hepatol 2026;32(2):953-956.
Published online September 1, 2025; DOI: https://doi.org/10.3350/cmh.2025.0962

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Correspondence to editorial on “Human cytomegalovirus reactivation in cirrhosis patients with acute decompensation”
Changze Hong, Jinjun Chen
Clinical and Molecular Hepatology.2026; 32(3): e336. CrossRef

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Correspondence to letter to the editor on "Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States": Pojsakorn Danpanichkul, Luis Antonio Diaz, Juan Pablo Arab, Amit G. Singal, Ju Dong Yang; Clin Mol Hepatol 2026;32(3):e399-e401.
Published online September 1, 2025; DOI: https://doi.org/10.3350/cmh.2025.0948

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Letter to the editor on “High Steatosis-Associated Fibrosis Estimator scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic dysfunction-associated steatotic liver disease”: Prajnasini Satapathy, Rachana Mehta, Ranjana Sah; Clin Mol Hepatol 2026;32(2):e139-e140.
Published online August 8, 2025; DOI: https://doi.org/10.3350/cmh.2025.0875

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SAFE score in chronic liver diseases: A tool for risk enrichment and personalized surveillance: Correspondence to letter to the editor on “High Steatosis-Associated Fibrosis Estimator scores predict hepatocellular carcinoma in viral and non-viral hepatiti
Tung-Hung Su, Jia-Horng Kao
Clinical and Molecular Hepatology.2026; 32(3): e396. 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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Journal of Gastroenterology and Hepatology.2025; 40(11): 2750. CrossRef

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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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Human cytomegalovirus reactivation in cirrhosis patients with acute decompensation: Changze Hong, Zuxiong Huang, Yingli He, Rongqi Wang, Jiaying Lin, Yushan Liu, Baicheng Liu, Xiaoqin Lan, Qinjun He, Wenfan Luo, Qintao Lai, Ling Zhou, Tingting Qi, Yali Ji, Miaoxia Liu, Qiaoping Wu, Yichen Yao, Weihao Liang, Xianbo Wang, Guohong Deng, Yanhang Gao, Yan Huang, Feng Liu, Xiaobo Lu, Zhongji Meng, Yuemin Nan, Hai Li, Beiling Li, Rajiv Jalan, Jinjun Chen; Clin Mol Hepatol 2025;31(4):1316-1332.
Published online July 4, 2025; DOI: https://doi.org/10.3350/cmh.2025.0332

Background/Aims
The role of reactivation of human cytomegalovirus (HCMV) in determining outcomes of cirrhotic patients with acute decompensation (AD) is unknown. We aimed to investigate HCMV incidence and potential correlation with hepatic outcomes in AD patients.
Methods
Two prospective multicentre cohorts with AD patients were investigated. Patients in cohort 1 were recruited from 4 centres, while patients in cohort 2 were randomly selected from a second multicentre cohort. HCMV reactivation was established with quantitative real-time polymerase chain reaction assay in seropositive patients.
Results
HCMV reactivation was found in 35 patients from cohort 1 (n=722) and 14 from cohort 2 (n=291), with an incidence of 4.8% in both cohorts. Bacterial infection and liver failure were independently correlated with HCMV reactivation. HCMV reactivation was an independent predictor of 90-day mortality. Among bacterial infection populations in these two cohorts, patients with HCMV reactivation had worse prognosis compared to those without. Incidence of acute-on-chronic liver failure (ACLF) was higher in patients with HCMV reactivation compared to those without and was also independently correlated with development of ACLF. In a total of 49 HCMV reactivation cases, 8 patients were treated with ganciclovir, in whom a significantly lower 90-day mortality compared with those not treated was observed. All 3 patients who underwent liver transplantation with reactivation of HCMV died.
Conclusions
In AD patients, HCMV reactivation was common, especially in those with bacterial infection or liver failure, and they were more prone to having ACLF and 90‑day mortality. The data propose the need for active surveillance for HCMV infection in AD patients.

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Correspondence to letter to the editor on “Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States”: Pojsakorn Danpanichkul, Luis Antonio Diaz, Juan Pablo Arab, Amit G. Singal, Ju Dong Yang; Clin Mol Hepatol 2026;32(2):e246-e248.
Published online June 17, 2025; DOI: https://doi.org/10.3350/cmh.2025.0594

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Stable Nationwide Sepsis-Related Mortality Does Not Extend to Individuals with Alcohol-Associated Liver Disease
Pojsakorn Danpanichkul, Kwanjit Duangsonk, Claire S. Faulkner, Supapitch Sirimangklanurak, Tulaton Sodsri, Natchaya Polpichai, Shu-Yen Chan, Yanfang Pang, Omar Y. Mousa, Donghee Kim, Suthat Liangpunsakul, Karn Wijarnpreecha
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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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3,330 View
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Advancing policy and practice in alcohol-associated liver disease and alcohol-attributable cancer: Correspondence to the editorial on “Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States”: Pojsakorn Danpanichkul, Donghee Kim, Karn Wijarnpreecha, Amit G. Singal, Ju Dong Yang; Clin Mol Hepatol 2026;32(1):e96-e98.
Published online May 15, 2025; DOI: https://doi.org/10.3350/cmh.2025.0527

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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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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”
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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”
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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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5,129 View
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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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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
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Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States: Pojsakorn Danpanichkul, Yanfang Pang, Tanuj Mahendru, Primrose Tothanarungroj, Luis Antonio Díaz, Juan Pablo Arab, Pimtawan Jatupornpakdee, Mark D. Muthiah, Kwanjit Duangsonk, Won-Mook Choi, Daniel Q. Huang, Donghee Kim, Mazen Noureddin, Karn Wijarnpreecha, Suthat Liangpunsakul, Amit G. Singal, Ju Dong Yang; Clin Mol Hepatol 2025;31(3):1058-1070.
Published online April 11, 2025; DOI: https://doi.org/10.3350/cmh.2025.0169

Background/Aims
Harmful alcohol use is a substantial contributor to liver diseases, liver cancer, and extrahepatic neoplasms. Patterns of alcohol consumption have shifted over recent decades. This study evaluates trends in alcohol-associated liver disease (ALD) and alcohol-attributable cancers in the United States (US) from 2000 to 2021.
Methods
Using the methodological framework of the Global Burden of Disease Study 2021, we analyzed trends in incidence, prevalence, and mortality from ALD and alcohol-attributable cancers in the US.
Results
In 2021, there were 28,340 new cases of ALD, 227,730 prevalent cases, and 21,860 deaths attributed to ALD in the US. From 2000 to 2021, ALD incidence, prevalence, and mortality increased by 43%, 36%, and 79%, respectively. The age-standardized incidence and death rate of ALD rose disproportionately among females compared to males. For alcohol-attributable cancers, primary liver cancer, colorectal cancer, and esophageal cancer accounted for the largest share of deaths in 2021. Age-standardized death rates increased significantly for primary liver cancer (annual percent change [APC] 2.21%, 95% confidence interval [CI] 1.70–2.73%) and other pharyngeal cancer (APC 1.35%, 95% CI 1.08–1.62%).
Conclusions
The burden of ALD is substantial and continues to rise in the US, with a particularly notable increase among females. Mortality from alcohol-attributable cancers is also increasing, mainly driven by primary liver cancer and pharyngeal cancer. However, system-wise, gastrointestinal cancer had the highest death attributable to alcohol. These findings highlight the urgent need for public health strategies to tackle ALD, primary liver cancer, and alcoholattributable extrahepatic malignancies.

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Advancing policy and practice in alcohol-associated liver disease and alcohol-attributable cancer: Correspondence to the editorial on “Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the Unite
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Akira Yokoyama, Tetsuji Yokoyama
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Chinmay T. Jani, Kyle Edwards, Rajesh Sharma, Ruchi T. Jani, Ali Al Sbihi, Jose Noy, Georges Chedid, Samuel Kareff, Joseph Shalhoub, Justin Salciccioli, Dionysios C. Watson, Aman Chauhan, Estelamari Rodriguez, Gilberto Lopes
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Global epidemiological patterns and disease burden of metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction and alcohol-associated liver disease, and alcohol-associated liver disease
Pojsakorn Danpanichkul, Matheus Souza, Primrose Tothanarungroj, Aijaz Ahmed, Donghee Kim
Clinical and Molecular Hepatology.2026; 32(Suppl): e2026.0444. CrossRef
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Yue Feng, PanShiLi Han, Tao Liu, YanHang Gao
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Sex Disparity in Major Adverse Liver Outcome and Major Adverse Cardiac Event in Alcohol‐Associated Liver Disease
Pojsakorn Danpanichkul, Donghee Kim, Karn Wijarnpreecha, Mark D. Muthiah, Suthat Liangpunsakul
Liver International.2025;[Epub] CrossRef
Effect of varenicline on major adverse liver outcomes in alcohol‐associated liver disease: An exploratory analysis
Pojsakorn Danpanichkul, Yanfang Pang, Donghee Kim, Thanathip Suenghataiphorn, Donghyun Ko, Andrew F. Ibrahim, Vitchapong Prasitsumrit, Kwanjit Duangsonk, Mazen Noureddin, Karn Wijarnpreecha, Suthat Liangpunsakul
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P. Huerta, J.P. Arab, L.A. Díaz
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Etiology of cirrhosis is associated with risk of hepatic decompensation and hepatocellular carcinoma
Michelle Ng, Olgert Bardhi, Krystal Lai, Eden Koo, Sruthi Yekkaluri, Kevin Bass, Guruveer Bhamra, Pojsakorn Danpanichkul, Lisa Quirk, Ju Dong Yang, Jeremy Louissaint, Thomas A. Kerr, Amit G. Singal
BMC Gastroenterology.2025;[Epub] CrossRef

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24 Web of Science
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Tracking the trajectory of kidney dysfunction in cirrhosis: the acute kidney injury: chronic kidney disease spectrum: Vishnu Girish, Rakhi Maiwall; Clin Mol Hepatol 2025;31(3):730-752.
Published online March 26, 2025; DOI: https://doi.org/10.3350/cmh.2024.1060

Abstract
PDF

Kidney disease in cirrhosis is now viewed as a continuum encompassing acute kidney injury (AKI), acute kidney disease (AKD), and chronic kidney disease (CKD), rather than three different disorders. Contemporary diagnostic criteria for AKI integrate urine output (UO) parameters and acknowledge the intricate relationship and possibility of overlap between functional and structural as well as acute and chronic entities, including hepatorenal syndrome (HRS). AKI demonstrates a propensity for progression to AKD and CKD, particularly in the context of recurrent and severe insults. The diagnostic complexity is further compounded by limitations in serum creatinine measurements, prompting the integration of novel biomarkers and the need to accurately estimate glomerular filtration rate. The diagnosis, phenotyping, and management of AKI should be prompt and early; the initial step should always be volume and UO assessment. A personalized approach is needed and the possibility of co-existing structural or functional kidney disease should be borne in mind. The earlier concept of waiting for 48 hours to diagnose HRS has evolved and early diagnosis and prompt treatment are advised now. Kidney replacement therapy and simultaneous liver and kidney transplantation may be required in resistant cases.

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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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Emerging evidence supports direct-acting antiviral therapy for HCC patients beyond the early stage: Correspondence to editorial on “Direct-acting antiviral therapy for patients with HCV-related hepatocellular carcinoma: A nationwide cohort study”: Teng-Yu Lee, Pei-Chien Tsai, Shou-Wu Lee, Ming-Lung Yu; Clin Mol Hepatol 2026;32(1):e68-e71.
Published online March 4, 2025; DOI: https://doi.org/10.3350/cmh.2025.0235

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Should direct-acting antiviral be considered for all patients with HCV-related hepatocellular carcinoma?: Reply to correspondence on “Direct-acting antiviral therapy for patients with HCV-related hepatocellular carcinoma: A nationwide cohort study”
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Direct-acting antiviral therapy for patients with hepatitis C virus-related hepatocellular carcinoma: A nationwide cohort study: Shou-Wu Lee, Sheng-Shun Yang, Pei-Chien Tsai, Chung-Feng Huang, Chi-Yi Chen, Chao-Hung Hung, Chien-Hung Chen, Chi-Ming Tai, Pin-Nan Cheng, Hsing-Tao Kuo, Kuo-Chih Tseng, Lein-Ray Mo, Ching-Chu Lo, Yi-Hsiang Huang, Han-Chieh Lin, Pei-Lun Lee, Ming-Jong Bair, Te-Sheng Chang, Chun-Yen Lin, Szu-Jen Wang, Tsai-Yuan Hsieh, Tzeng-Hue Yang, Cheng-Yuan Peng, Chi-Chieh Yang, Lee-Won Chong, Chien-Wei Huang, Chih-Wen Lin, Cheng-Hsin Chu, Ming-Chang Tsai, Jia-Horng Kao, Chun-Jen Liu, Wan-Long Chuang, Teng-Yu Lee, Ming-Lung Yu, on behalf of TACR investigators; Clin Mol Hepatol 2025;31(3):899-913.
Published online February 5, 2025; DOI: https://doi.org/10.3350/cmh.2024.1015

Background/Aims
The survival benefit of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection in patients with hepatocellular carcinoma (HCC), particularly in Barcelona Clinic Liver Cancer (BCLC) stages B/C, remains largely uncertain. We aimed to explore the impact of DAA therapy on overall survival (OS) in HCC patients using a nationwide cohort study.
Methods
We utilized the nationwide Taiwan Association for the Study of the Liver (TASL) HCV Registry (TACR) database to include all adults receiving a DAA therapy for HCV, excluding those with other viral infections, liver transplantation, non-HCC malignancies, and terminal-staged HCC. We respectively analyzed the adjusted odds ratio (aOR) for sustained virological response (SVR) and adjusted hazard ratio (aHR) for OS.
Results
Between December 2013 and December 2020, 2,205 (9.3%) patients with HCC and 21,569 (90.7%) patients without HCC were include. The SVR rates were 96.6% in the HCC group and 98.8% in the non-HCC group (P<0.001), with HCC being an independent risk factor affecting SVR (aOR 0.41; 95% CI 0.31–0.54; P<0.001). In the whole patient cohort, SVR was independently associated with improved OS (aHR 0.46; 95% CI 0.35–0.60; P<0.001). Among patients with baseline HCC, SVR remained an independent factor related to OS (aHR 0.41; 95% CI 0.28–0.59; P<0.001). The impact of SVR on OS persisted significantly across BCLC stages 0/A and stages B/C.
Conclusions
High SVR rates among HCC patients underscore the importance of DAA therapy in enhancing OS, reaffirming its efficacy across various HCC stages.

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Revisiting unmet needs in clinical research on direct-acting antiviral therapy for HCC patients: Correspondence to letter to the editor on “Direct-acting antiviral therapy for patients with HCV-related hepatocellular carcinoma: A nationwide cohort study”
Teng-Yu Lee, Pei-Chien Tsai, Shou-Wu Lee, Ming- Lung Yu
Clinical and Molecular Hepatology.2026; 32(1): e99. CrossRef
Emerging evidence supports direct-acting antiviral therapy for HCC patients beyond the early stage: Correspondence to editorial on “Direct-acting antiviral therapy for patients with HCV-related hepatocellular carcinoma: A nationwide cohort study”
Teng-Yu Lee, Pei-Chien Tsai, Shou-Wu Lee, Ming-Lung Yu
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Survival impact of hepatitis C virus eradication in patients with or without active hepatocellular carcinoma: A nationwide cohort study
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Qiong Wang, Zhongqing Qian, Xiaodi Yang, Deyan Chen, Xiaojing Wang, Fuliang Chen
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María Fernanda Guerra‐Veloz, Sital Shah, Beatrice Emmanouil, Mia Olsen, Renita George, Sarah Selemani, Paul J. Ross, Ivana Carey, Neha Mehta, Mark Gillyon‐Powell, Kosh Agarwal
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Letter: Methodological Considerations in Interpreting Polygenic Risk Scores for Hepatocellular Carcinoma After SVR. Authors' Reply
Yu‐Sheng Lin, Yun‐Yu Chen, Teng‐Yu Lee
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Yu‐Sheng Lin, Hwai‐I Yang, Teng‐Yu Lee
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Letter: Beyond Association—Operationalising PRS‐5 for Hepatocellular Carcinoma Surveillance. Authors' Reply
Yu‐Sheng Lin, Ying‐Cheng Lin, Teng‐Yu Lee
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Taotao Yan, Pei-Chien Tsai, Ming-Lun Yeh, Dae Won Jun, Hidenori Toyoda, Yao-Chun Hsu, Jennifer Leong, Xiaozhong Wang, Xu Qiang, Hiroshi Abe, Takanori Suzuki, Chia-Yen Dai, Jee-Fu Huang, Wan-Long Chuang, Chung-Feng Huang, Yao-Li Chen, Ping-Yi Lin, Satoshi
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Nadeem Ashraf, Qingyong Hong, Zhidong Guo, Kun Li
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Shunsuke Sato, Masahiro Yamaguchi, Hiroki Nago, Yoko Kato, Rihwa Om, Yuichiro Terai, Yuji Kita, Yuji Ikeda, Sho Sato, Ayato Murata, Yuji Shimada, Takuya Genda
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Khumbuzile Canham, Pragalathan Naidoo, Sibusiso Senzani, Sayed Shakeel Kader, Zilungile L. Mkhize-Kwitshana
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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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Liver Transplantation

Intrapatient variability of tacrolimus trough level may be not the cause, but an indirect parameter of comorbidities: Editorial on “Optimal tacrolimus levels for reducing CKD risk and the impact of intrapatient variability on CKD and ESRD development following liver transplantation”: Jongman Kim; Clin Mol Hepatol 2025;31(2):589-591.
Published online January 24, 2025; DOI: https://doi.org/10.3350/cmh.2025.0076

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Correspondence to editorial on “Optimal tacrolimus levels for reducing CKD risk and the impact of intrapatient variability on CKD and ESRD development following liver transplantation”
Soon Kyu Lee, Jong Young Choi
Clinical and Molecular Hepatology.2025; 31(2): e161. 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
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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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Published online January 9, 2025; DOI: https://doi.org/10.3350/cmh.2024.1159

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Correspondence to letter to the editor on “Optimal tacrolimus levels for reducing CKD risk and the impact of intrapatient variability on CKD and ESRD development following liver transplantation”
Soon Kyu Lee, Jong Young Choi
Clinical and Molecular Hepatology.2025; 31(2): e212. CrossRef

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Published online December 23, 2024; DOI: https://doi.org/10.3350/cmh.2024.1138

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