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Review

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
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.
  • 1,430 View
  • 104 Download

Special Issue

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

Citations

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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
  • 2,657 View
  • 273 Download
  • Crossref

Research Letter

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
  • 1,169 View
  • 149 Download

Correspondence

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
  • 904 View
  • 13 Download

Letters to the Editor

Citations

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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
  • 711 View
  • 57 Download
  • Crossref

Citations

Citations to this article as recorded by  Crossref logo
  • 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
  • 1,021 View
  • 85 Download
  • Crossref

Review

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
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.

Citations

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  • Current Status and Prospects of Clinical Research on Low-Level Viremia in Chronic Hepatitis B after Treatment
    颜 刘
    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
  • 3,701 View
  • 278 Download
  • 1 Web of Science
  • Crossref

Letter to the Editor

Editorial

Review

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
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.

Citations

Citations to this article as recorded by  Crossref logo
  • 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
  • Zinc finger protein ZBTB7A suppresses hepatitis B virus replication by attenuating FXRα-mediated HBV transcription and lowering covalently closed circular DNA levels
    Dan Xu, Zhenyu Zhao, Beinu Guo, Zhen Wei, Chen Li, Sichen Luo, Wen Shu, Zhongliang Shen, Mengji Lu, Jiming Zhang, Hecun Zou, Fahong Li, Yong Lin
    Antiviral Research.2026; 252: 106469.     CrossRef
  • Hepatitis B Research in Peru, 1988–2023: Geographic Inequities, Thematic Gaps, and Misalignment with Disease Burden
    Jhon Omar Palomino-Tenorio, Obert Marín-Sánchez, Jimmy Ango-Bedriñana, Ruy D. Chacón, Homero Ango-Aguilar
    Pathogens.2026; 15(7): 708.     CrossRef
  • Supramolecular Self-Assembly of Lycorine with Glycyrrhizic Acid into a Nanodrug for Safe and Sustained Anti-HBV Therapy
    Hang Sun, Zi-Dong He, Bei-Bei Jia, Bo Yuan, Ling-Chuan Kong, Rui-Xian Xu, Qiong Wang, Wen-Jing Pan, Hao Chen, Shao-Xing Dai, Min Xu
    ACS Applied Bio Materials.2026; 9(15): 7143.     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
  • 8,603 View
  • 291 Download
  • 8 Web of Science
  • Crossref

Letter to the Editor

Reply to Correspondence

  • 4,395 View
  • 31 Download

Correspondences

Citations

Citations to this article as recorded by  Crossref logo
  • 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
  • 3,838 View
  • 16 Download
  • Crossref

Citations

Citations to this article as recorded by  Crossref logo
  • 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
  • 2,970 View
  • 20 Download
  • Crossref

Research Letter

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
  • 9,427 View
  • 85 Download

Editorial

Citations

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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
  • 3,785 View
  • 60 Download
  • 1 Web of Science
  • Crossref

Correspondence

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
  • 4,720 View
  • 49 Download

Editorial

Citations

Citations to this article as recorded by  Crossref logo
  • 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; 49(3): 100969.     CrossRef
  • The Chronic Hepatitis B and Metabolic Dysfunction-Associated Steatotic Liver Disease Paradox: Friend or Foe?
    Shang-Chin Huang, Tai-Chung Tseng
    Gut and Liver.2026; 20(3): 350.     CrossRef
  • Insulin Resistance and Hepatocellular Carcinoma Development in Chronic Hepatitis B Patients Under Antiviral Therapy
    Dong Hyun Sinn, Kyung-Ah Kim, Jung Il Lee, Geum-Youn Gwak
    Journal of Korean Medical Science.2026;[Epub]     CrossRef
  • 5,442 View
  • 51 Download
  • 2 Web of Science
  • Crossref

Original Article

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.

Citations

Citations to this article as recorded by  Crossref logo
  • Type 2 diabetes mellitus as an independent predictor of significant fibrosis in treatment-naïve chronic hepatitis B patients with concurrent hepatic steatosis
    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
    Hepatology.2026; 83(5): 1273.     CrossRef
  • 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
  • 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
    Clinical and Molecular Hepatology.2026; 32(1): 423.     CrossRef
  • Diagnosis and management of metabolic dysfunction-associated steatohepatitis in patients with chronic hepatitis B infection
    Talal K Bhatti, Joseph K Lim
    World Journal of Gastroenterology.2026;[Epub]     CrossRef
  • Diabetes Impairs the Virological Response in Patients with Chronic Hepatitis B: Glycemic Control as a Key Modifiable Risk Factor
    Aoyi Li, Yan Han, Guanglin Xiao, Zhiling Deng, Chaojing Wen, Ke Qiu, Taiyu He, Hong Ren
    Journal of Clinical Medicine.2026; 15(5): 1826.     CrossRef
  • Antiviral Therapy Reduces Hepatocellular Carcinoma and Cirrhosis Risk in Chinese Chronic Hepatitis B Patients With Mildly Elevated Alanine Aminotransferase
    Jian Wang, Zhiyi Zhang, Li Zhu, Tao Fan, Ye Xiong, Shaoqiu Zhang, Chao Jiang, Shengxia Yin, Xin Tong, Juan Xia, Xiaomin Yan, Renling Yao, Yu Shi, Xingxiang Liu, Chuanwu Zhu, Chao Wu, Rui Huang
    Clinical Gastroenterology and Hepatology.2026;[Epub]     CrossRef
  • Steatosis paradox: Unraveling pathways of suppressive effect of hepatic steatosis on hepatitis B virus
    Shang-Chin Huang, Jia-Horng Kao
    Biomedical Journal.2026; 49(3): 100969.     CrossRef
  • Impact of Cardiometabolic Risk Factors and Steatotic Liver Disease on Liver‐Related Outcomes in Patients With Chronic Hepatitis C After Curative Antiviral Therapy
    Chung‐Feng Huang, Yi‐Hung Lin, Pei‐Chien Tsai, Ming‐Lun Yeh, Chih‐Wen Wang, Tyng‐Yuan Jang, Po‐Cheng Liang, Yu‐Ju Wei, Nai‐Jen Hou, Ming‐Yen Hsieh, Chao‐Kuan Huang, Tzu‐Chun Lin, Jee‐Fu Huang, Chia‐Yen Dai, Wan‐Long Chuang, Ming‐Lung Yu
    The Kaohsiung Journal of Medical Sciences.2026;[Epub]     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
  • Diagnosing and defining MASLD in people living with chronic hepatitis B
    Emily Martyn, Alejandro Arenas-Pinto, Richard Gilson, Nomathemba Chandiwana, Stuart Flanagan, Douglas MacDonald, Emmanuel A. Tsochatzis, W. D. Francois Venter, Jennifer Manne-Goehler, Philippa C. Matthews
    Communications Medicine.2026;[Epub]     CrossRef
  • The Chronic Hepatitis B and Metabolic Dysfunction-Associated Steatotic Liver Disease Paradox: Friend or Foe?
    Shang-Chin Huang, Tai-Chung Tseng
    Gut and Liver.2026; 20(3): 350.     CrossRef
  • Insulin Resistance and Hepatocellular Carcinoma Development in Chronic Hepatitis B Patients Under Antiviral Therapy
    Dong Hyun Sinn, Kyung-Ah Kim, Jung Il Lee, Geum-Youn Gwak
    Journal of Korean Medical Science.2026;[Epub]     CrossRef
  • Efficacy and Safety of Switching from Entecavir to Tenofovir Alafenamide in Chronic Hepatitis B: A Multicenter Randomized Trial in Korea
    Hyunjae Shin, Moon Haeng Hur, Yang Hyun Baek, Chun Kyon Lee, Yong Kyun Cho, June Sung Lee, Jae Yoon Jeong, Yong Jin Jung, Ja Kyung Kim, Moon Young Kim, Yeon Seok Seo, Woo Jin Chung, Moon Soo Koh, Jeong-Han Kim, Yun Bin Lee, Eun Ju Cho, Jeong-Hoon Lee, Su
    Gut and Liver.2026; 20(4): 636.     CrossRef
  • Differential HCC risk among HBV indeterminate types at baseline and by phase transition
    Rui Huang, Huy N Trinh, Satoshi Yasuda, Angela Chau, Mayumi Maeda, Ai-Thien Do, Daniel Q Huang, Takanori Ito, Takashi Honda, Masatoshi Ishigami, Ritsuzo Kozuka, Carmen Monica Preda, Cheng-Hao Tseng, Sebastián Marciano, Pei-Chien Tsai, Dong Hyun Lee, Chris
    Gut.2025; 74(11): 1873.     CrossRef
  • Incidence and determinants of achieving HBsAg <100 IU/mL in HBeAg-negative CHB patients with nucleos(t)ide analogue treatment
    Jian Wang, Tao Fan, Zhiyi Zhang, Li Zhu, Shaoqiu Zhang, Ye Xiong, Chun Shan, Chao Jiang, Shengxia Yin, Xin Tong, Renling Yao, Juan Xia, Xiaomin Yan, Yu Shi, Yuxin Chen, Xingxiang Liu, Huali Wang, Haixia Zhang, Chuanwu Zhu, Qun Zhang, Chao Wu, Rui Huang
    Emerging Microbes & Infections.2025;[Epub]     CrossRef
  • Impact of metabolic dysfunction on treatment responses to nucleos(t)ide analogues in chronic hepatitis B: a retrospective multi-center REAL-B cohort study
    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 Ats
    eClinicalMedicine.2025; 87: 103407.     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
  • Multifunctional Metal Composite Hydrogels for Diabetic Wound Therapy
    Shengnan Zhang, Hui Gao, Kevin H. Mayo, Jingang Mo, Le Deng
    Gels.2025; 11(12): 960.     CrossRef
  • 15,683 View
  • 265 Download
  • 21 Web of Science
  • Crossref

Correspondence

Citations

Citations to this article as recorded by  Crossref logo
  • 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
  • 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”
    Yan Ling Ong, Apichat Kaewdech, Yu Jun Wong
    Clinical and Molecular Hepatology.2026; 32(1): e109.     CrossRef
  • The Clinical Use of Stem Cells in Liver Cancer Treatment: Interactions Between Diet, Metabolic Disease and Hepatic Regeneration
    Julia Coelho Moura, Vincent S Gallicchio
    Journal of Regenerative Medicine and Biology Research.2026; 7(2): 1.     CrossRef
  • 5,748 View
  • 48 Download
  • 1 Web of Science
  • Crossref

Original Articles

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.

Citations

Citations to this article as recorded by  Crossref logo
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  • Crossref
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.

Citations

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Review

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
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

Letter to the Editor

Viral hepatitis

Citations

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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
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Review

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
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.

Citations

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    Markus Cornberg, Ulrike Protzer
    Deutsches Ärzteblatt Online.2025;[Epub]     CrossRef
  • Structural optimization of phthalazine derivatives for anti-HBV activities to improve oral bioavailability
    Yurong Yang, Fuling Xiao, Jianping Zuo, Li Yang, Youhong Hu, Wuhong Chen
    Bioorganic & Medicinal Chemistry.2025; 128: 118259.     CrossRef
  • Emerging therapies for HBsAg seroclearance: spotlight on novel combination strategies
    Rex Wan-Hin Hui, James Fung, Wai-Kay Seto, Man-Fung Yuen, Lung-Yi Mak
    Hepatology International.2025; 19(4): 704.     CrossRef
  • Advancing HIV cure: insights from developing chronic hepatitis b therapies for functional cure
    Ana Verma, Raymond T. Chung
    Current Opinion in HIV and AIDS.2025; 20(5): 449.     CrossRef
  • Challenges and advances in clinical cure of chronic hepatitis B
    Xu-Ling Liu, Yu-Lang Jiang, Ming-Yu Sun
    World Chinese Journal of Digestology.2025; 33(9): 693.     CrossRef
  • Small molecule HBV RNA destabilizing drugs: Drugs of the future or compounds from the past?
    Timothy M. Block, Dimitar Gotchev, Yanming Du
    Antiviral Research.2025; 244: 106288.     CrossRef
  • Global strategies and actions to eliminate hepatitis B virus infection
    Chih-Lin Lin, Jia-Horng Kao
    Clinical and Molecular Hepatology.2025; 31(4): 1197.     CrossRef
  • Morphometric and structural dynamic parameters of hepatitis viruses: implications for therapeutic and vaccine failure
    Saganuwan Alhaji Saganuwan
    Discover Viruses.2025;[Epub]     CrossRef
  • Functional cure of chronic hepatitis B virus infection: current therapeutic regimens
    Yi-Wei Shi, Rui Pu, Yi-Bo Ding, Wen-Bin Liu, Zi-Shuai Li, Jia-Yi Zhao, Yi-Fan Chen, Guang-Wen Cao
    Hepatoma Research.2025;[Epub]     CrossRef
  • 16,732 View
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Reply to Correspondence

Editorial

Viral hepatitis

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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
  • 6,627 View
  • 35 Download
  • 1 Web of Science
  • Crossref

Letter to the Editor

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
  • 6,860 View
  • 43 Download

Original Article

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.
  • 9,039 View
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  • 6 Web of Science

Correspondence

Viral hepatitis

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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
  • 5,945 View
  • 32 Download
  • 1 Web of Science
  • Crossref

Editorials

Viral hepatitis

Citations

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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
  • 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
  • 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
  • 8,249 View
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  • 3 Web of Science
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  • Understanding liver and digestive diseases: a paved road to improve diagnosis, management, and treatment
    Ina Bergheim, Jean Francois Cadranel, Jianguo Chen, Wenxing Ding, Robert Eferl, Carmen Garcia-Ruiz, Hartmut Jaeschke, Firouzeh Kazerouni, Amedeo Lonardo, Derek A. Mann, Nahum Méndez-Sánchez, Camelia Mokhtari, Han Moshage, Chiara Raggi, Pavel Strnad, Oren
    Exploration of Digestive Diseases.2026;[Epub]     CrossRef
  • Optimizing hepatitis C micro-elimination in forensic psychiatric settings: Cost-effectiveness of screening strategies in Korea
    Gyeongseon Shin, Sang Hoon Ahn, Hankil Lee, Beom Kyung Kim
    Journal of Infection and Public Health.2026; 19(9): 103331.     CrossRef
  • 9,121 View
  • 68 Download
  • Crossref

Letter to the Editor

Viral hepatitis

Citations

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  • Correspondence to letter to the editor on “Non-linear association between liver fibrosis scores and viral load in patients with chronic hepatitis B”
    Gi-Ae Kim, Seung Won Choi, Young-Suk Lim
    Clinical and Molecular Hepatology.2025; 31(1): e108.     CrossRef
  • 8,068 View
  • 71 Download
  • Crossref

Original Articles

Viral hepatitis

Vibration-controlled transient elastography for significant fibrosis in treatment-naïve chronic hepatitis B patients: A systematic review and meta-analysis
Mi Na Kim, Jihyun An, Eun Hwa Kim, Hee Yeon Kim, Han Ah Lee, Jung Hwan Yu, Young-Joo Jin, Young Eun Chon, Seung Up Kim, Dae Won Jun, Ji Won Han, Miyoung Choi
Clin Mol Hepatol 2024;30(Suppl):S106-S116.
Published online July 23, 2024
DOI: https://doi.org/10.3350/cmh.2024.0371
Backgrounds/Aims
Accurate diagnosis of significant liver fibrosis in patients with chronic hepatitis B (CHB) is crucial when determining whether to initiate antiviral treatment (AVT). We conduct a meta-analysis to assess the diagnostic performance of vibration-controlled transient elastography (VCTE) for significant liver fibrosis in AVT-naïve CHB patients with serum alanine transaminase (ALT) levels within 5-fold the upper limit of normal (ULN).
Methods
The Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases were searched to identify studies that compared the performance of VCTE and liver biopsy (reference standard) when diagnosing significant liver fibrosis (≥F2) in AVT-naïve CHB patients with ALT within 5-fold the ULN. A hierarchical summary receiver operating characteristic curve (HSROC) and bivariate model were performed to evaluate the diagnostic performance of VCTE in the meta-analysis.
Results
Eight studies (2,003 patients) were included. The summary sensitivity and specificity for diagnosis of significant liver fibrosis were 0.78 (95% confidence interval [CI], 0.66–0.86) and 0.72 (95% CI, 0.60–0.82), respectively. The HSROC for the diagnosis of significant liver fibrosis was 0.81 (95% CI, 0.72–0.86). The optimal cutoff value of VCTE for diagnosis of significant liver fibrosis was 7.7 kPa with a sensitivity of 0.64 (95% CI, 0.50–0.76) and specificity of 0.83 (95% CI, 0.72–0.90).
Conclusions
Our study demonstrated that VCTE has an acceptable diagnostic performance for significant liver fibrosis in AVT-naïve CHB patients with ALT within 5-fold the ULN.

Citations

Citations to this article as recorded by  Crossref logo
  • Chronic Hepatitis B Infection: Patient Guidance
    Lung‐Yi Mak, Jimmy Che‐To Lai, Ken Liu, Rashid Lui, Sakkarin Chirapongsathorn, Kuo Chao Yew, Mara Teresa Panlilio, Cosmas Rinaldi Adithya Lesmana, Ruveena Bhavani Rajaram, Liang Shen, Desmond Cheung, Lung‐Fai Wong, Hye Won Lee, Madhumita Premkumar, Anand 
    Journal of Gastroenterology and Hepatology.2026; 41(1): 61.     CrossRef
  • APASL clinical practice guidelines on the management of chronic hepatitis B infection: a 2026 update
    Hong You, Rakhi Maiwall, Jing Chen, Sang Hoon Ahn, Kadir Dokmeci, Xiaoguang Dou, Manal El-Sayed, Jian-Gao Fan, Rino Gani, Zhiliang Gao, Jacob George, Hasmik Ghazinian, George Goh, Saeed Hamid, Jinlin Hou, Shang-Chin Huang, Dong Ji, Jidong Jia, Tatsuo Kand
    Hepatology International.2026;[Epub]     CrossRef
  • Unraveling Demographic Patterns in Hepatitis B Clinical and Laboratory Profiles: Insights From a Ghanaian Cohort: A Retrospective Study
    Napoleon Bellua Sam, Saeed Folorunsho Majeed, Adams Dramani
    Health Science Reports.2025;[Epub]     CrossRef
  • Head‐to‐Head Comparison of Long‐Term HCC Risk of Antivirals‐Treated Versus Untreated Low‐Level Viremia in HBV‐Compensated Cirrhosis
    Nobuharu Tamaki, Daniel Q. Huang, Hyung Woong Lee, Soo Young Park, Yu Rim Lee, Dong Hyun Sinn, Tae Seop Lim, Hiroyuki Marusawa, Seng Gee Lim, Hironori Ochi, Masahiko Kondo, Yasushi Uchida, Haruhiko Kobashi, Koichiro Furuta, Masayuki Kurosaki, Beom Kyung K
    Journal of Gastroenterology and Hepatology.2025; 40(6): 1595.     CrossRef
  • Assessing Liver Fibrosis in Chronic Hepatitis B: Liver Biopsy or Non-Invasive Fibrosis Markers?
    Deniz Borcak, Zuhal Yesilbag, Yusuf Emre Ozdemir, Adile Sevde Demir, Esra Salim Dogdas, Aysegul Inci Sezen, Esra Canbolat Unlu, Sevtap Senoglu, Hayat Kumbasar Karaosmanoglu, Kadriye Kart Yasar
    Journal of Clinical Medicine.2025; 14(22): 8164.     CrossRef
  • Vibration-Controlled Transient Elastography in Chronic Liver Disease: Current Research Insights
    Ho Soo Chun
    Clinical Ultrasound.2025; 10(2): 69.     CrossRef
  • Recent Trends in Noninvasive Tests for Assessing Hepatic Fibrosis in Patients with Chronic Liver Disease
    Jung Hwan Yu
    The Korean Journal of Medicine.2024; 99(5): 232.     CrossRef
  • Noninvasive Imaging Test to Assess Liver Fibrosis: Vibration-controlled Transient Elastography
    Mi Na Kim
    The Korean Journal of Gastroenterology.2024; 84(5): 201.     CrossRef
  • Liver Fibrosis Assessment in Chronic Liver Diseases Using Elastography: A Comprehensive Review of Vibration-Controlled Transient Elastography and Shear Wave Elastography
    Han Ah Lee
    Clinical Ultrasound.2024; 9(2): 70.     CrossRef
  • 7,749 View
  • 153 Download
  • 7 Web of Science
  • Crossref

Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using vibration-controlled transient elastography: Systematic review and meta-analysis
Young-Joo Jin, Hee Yeon Kim, Young Ju Suh, Chae Hyeon Lee, Jung Hwan Yu, Mi Na Kim, Ji Won Han, Han Ah Lee, Jihyun An, Young Eun Chon, Dae Won Jun, Miyoung Choi, Seung Up Kim
Clin Mol Hepatol 2024;30(Suppl):S159-S171.
Published online July 23, 2024
DOI: https://doi.org/10.3350/cmh.2024.0163
Backgrounds/Aims
Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) can assess fibrotic burden in chronic liver diseases. The systematic review and meta-analysis was conducted to determine whether LSM using VCTE can predict the risk of development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients.
Methods
A systematic literature search of the Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases (from January 2010 to June 2023) was conducted. Of the 1,345 individual studies identified, 10 studies that used VCTE were finally registered. Hazard ratios (HRs) and the 95% confidence intervals (CIs) were considered summary estimates of treatment effect sizes of ≥11 kilopascal (kPa) standard for HCC development. Meta-analysis was performed using the restricted Maximum Likelihood random effects model.
Results
Among the ten studies, data for risk ratios for HCC development could be obtained from nine studies. When analyzed for the nine studies, the HR for HCC development was high at 3.33 (95% CI, 2.45–4.54) in CHB patients with a baseline LSM of ≥11 kPa compared to patients who did not. In ten studies included, LSM of ≥11 kPa showed the sensitivity and specificity for predicting HCC development were 61% (95% CI, 50–71%) and 78% (95% CI, 66–86%), respectively, and the diagnostic accuracy was 0.74 (95% CI, 0.70–0.77).
Conclusions
The risk of HCC development was elevated in CHB patients with VCTE-determined LSM of ≥11 kPa. This finding suggests that VCTE-determined LSM values may aid the risk prediction of HCC development in CHB patients.

Citations

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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
    Clinical and Molecular Hepatology.2026; 32(1): e58.     CrossRef
  • Enhanced Prediction of Hepatitis B Virus-Related Hepatocellular Carcinoma Using Age-Male-Albumin-Bilirubin-Platelet (aMAP) and Liver Stiffness Assessed by Vibration-Controlled Transient Elastography
    Hye Yeon Chon, Hyung Joon Yim, Seok-Jae Heo, Su Jong Yu, Ja Kyung Kim, Sang Hoon Ahn, Grace Lai-Hung Wong, Jimmy Che-To Lai, Terry Cheuk-Fung Yip, Sang Gyune Kim, Yeon Seok Seo, Seung Up Kim
    Clinical Gastroenterology and Hepatology.2026; 24(7): 1897.     CrossRef
  • Toward Precise Risk Stratification after the Functional Cure of Chronic Hepatitis B
    Moon Haeng Hur
    The Korean Journal of Gastroenterology.2026; 86(2): 71.     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
  • Hepatitis B Virus and Hepatocellular Carcinoma: Risk-Based Surveillance Strategies
    Abdelrahman M. Attia, Jessica Liu, Walid S Ayoub, Yun Wang, Aarshi Vipani, Paul Martin, Hyunseok Kim, Ju Dong Yang
    Current Hepatology Reports.2026;[Epub]     CrossRef
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    Xiaohuan Li, Yuhan Zhang, Zhiyuan Chen, Ke Wei, Yan Zhang, Xiying Zhao, Shuping Zhang, Ruhang Huang, Yupin Liu, Dongjing Zhou
    Insights into Imaging.2026;[Epub]     CrossRef
  • 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: S
    Mirko Zoncapè, Emmanuel A. Tsochatzis
    Clinical and Molecular Hepatology.2025; 31(1): 268.     CrossRef
  • Unraveling Demographic Patterns in Hepatitis B Clinical and Laboratory Profiles: Insights From a Ghanaian Cohort: A Retrospective Study
    Napoleon Bellua Sam, Saeed Folorunsho Majeed, Adams Dramani
    Health Science Reports.2025;[Epub]     CrossRef
  • A Review of Risk Prediction Model for Hepatocellular Carcinoma in Chronic Hepatitis B
    Jiwon Yang, Mark D. Muthiah, Won-Mook Choi
    Current Hepatology Reports.2025;[Epub]     CrossRef
  • Head‐to‐Head Comparison of Long‐Term HCC Risk of Antivirals‐Treated Versus Untreated Low‐Level Viremia in HBV‐Compensated Cirrhosis
    Nobuharu Tamaki, Daniel Q. Huang, Hyung Woong Lee, Soo Young Park, Yu Rim Lee, Dong Hyun Sinn, Tae Seop Lim, Hiroyuki Marusawa, Seng Gee Lim, Hironori Ochi, Masahiko Kondo, Yasushi Uchida, Haruhiko Kobashi, Koichiro Furuta, Masayuki Kurosaki, Beom Kyung K
    Journal of Gastroenterology and Hepatology.2025; 40(6): 1595.     CrossRef
  • Discovering the metabolic pathway of liver disease by breath mass spectrometry combined with machine learning
    Xuanzhu Li, Wenbo Zhang, Tongtong Yang, Ying Zhang, Rui Su
    Journal of Pharmaceutical and Biomedical Analysis.2025; 265: 116988.     CrossRef
  • Future Perspectives of Liver Research in the Asia‐Pacific Region: Focus on Hepatitis B and C
    Beom Kyung Kim
    Journal of Gastroenterology and Hepatology.2025; 40(8): 1855.     CrossRef
  • EASL 2025 indications revisited: phase-specific outcomes with and without nucleos(t)ide analogue therapy in chronic hepatitis B virus infection
    Shichuan Tang, Tingfeng Huang, Ruijing Tang, Kongying Lin, Cong Luo, Yubing Shen, Kailing Zhang, Yidan Tang, Jie Kong, Zhenwei Chen, Jun Fu, Qizhu Lin, Luobin Guo, Yeye Wu, Yuntong Li, Jianxi Zhang, Zhenghong Sun, Penghui You, Daichang Zhang, Yanxin Chen,
    Gut.2025; : gutjnl-2025-335449.     CrossRef
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    Xin Guan, Xinyuan Hu, Hong Han, Dezhi Zhang, Huixiong Xu
    Advanced Ultrasound in Diagnosis and Therapy.2025; 9(4): 375.     CrossRef
  • Transient Elastography and Fibroscan: Stethoscope of a Hepatologist in Today’s World
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    Current Hepatology Reports.2025;[Epub]     CrossRef
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  • 152 Download
  • 18 Web of Science
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Editorial

Reply to Correspondence

Viral hepatitis

  • 5,944 View
  • 64 Download

Correspondence

Viral hepatitis

Optimizing off-treatment outcome predictions: The potential of time-varying HBcrAg and the need for more research
Ying-Nan Tsai, Jia-Ling Wu, Yao-Chun Hsu
Clin Mol Hepatol 2024;30(2):276-278.
Published online April 1, 2024
DOI: https://doi.org/10.3350/cmh.2024.0220
  • 6,080 View
  • 51 Download

Original Articles

Viral hepatitis

Phase 1 trial of the safety, pharmacokinetics, and antiviral activity of EDP-514 in untreated viremic chronic hepatitis B patients
Man-Fung Yuen, Wan-Long Chuang, Cheng-Yuan Peng, Wen-Juei Jeng, Wei-Wen Su, Ting-Tsung Chang, Chi-Yi Chen, Yao-Chun Hsu, Guy De La Rosa, Alaa Ahmad, Ed Luo, Annie L. Conery
Clin Mol Hepatol 2024;30(3):375-387.
Published online March 26, 2024
DOI: https://doi.org/10.3350/cmh.2023.0535
Background/Aims
Oral EDP-514 is a potent core protein inhibitor of hepatitis B virus (HBV) replication, which produced a >4-log viral load reduction in HBV-infected chimeric mice with human liver cells. This study evaluated the safety, pharmacokinetics, and antiviral activity of three doses of EDP-514 in treatment-naive viremic patients with HBeAgpositive or -negative chronic HBV infection.
Methods
Patients with HBsAg detectable at screening and at least 6 months previously were eligible. HBeAg-positive and -negative patients had a serum/plasma HBV DNA level ≥20,000 and ≥2,000 IU/mL, respectively. Twenty-five patients were randomized to EDP-514 200 (n=6), 400 (n=6) or 800 mg (n=7) or placebo (n=6) once daily for 28 days.
Results
A dose-related increase in EDP-514 exposure (AUClast and Cmax) was observed across doses. At Day 28, mean reductions in HBV DNA were –2.9, –3.3, –3.5 and –0.2 log10 IU/mL with EDP-514 200 mg, 400 mg, 800 mg, and placebo groups, respectively. The corresponding mean change from baseline for HBV RNA levels was –2.9, –2.4, –2.0, and –0.02 log10 U/mL. No virologic failures were observed. No clinically meaningful changes from baseline were observed for HBsAg, HBeAg or HBcrAg. Nine patients reported treatment emergent adverse events of mild or moderate severity with no discontinuations, serious AEs or deaths.
Conclusions
In treatment-naïve viremic patients, oral EDP-514 was generally safe and well-tolerated, displayed PK profile supportive of once-daily dosing, and markedly reduced HBV DNA and HBV RNA.

Citations

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  • Navigating the Viral Hepatitis Drug Landscape: New Discoveries and Enduring Challenges. A Narrative Review
    He-ming Sun, Xing-yu Wang, Hong-qin Xu, Yan-hang Gao
    Infectious Diseases and Therapy.2026; 15(4): 959.     CrossRef
  • Emerging antiviral drugs and immunotherapy for chronic hepatitis B and associated liver disease
    Chunting Zhu, Jie Yang, Yu Sheng, Min Fang
    Frontiers in Immunology.2026;[Epub]     CrossRef
  • Functional cure with new antiviral therapy for hepatitis B virus: a systematic review and meta-analysis
    Jing Chen, Dong Ji, Jidong Jia, Hui Zhuang, Xinxin Zhang, Fu-Sheng Wang, Wenhong Zhang, Xiaoguang Dou, Tawesak Tanwandee, Shiv Kumar Sarin, Rakhi Maiwall, Manoj Kumar, George Boon-Bee Goh, Hasmik Ghazinyan, Anuchit Chutaputti, Pei-Jer Chen, Hong You, Ming
    Hepatology International.2025; 19(4): 773.     CrossRef
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    Marie Ongaro, Francesco Negro
    Schweizer Gastroenterologie.2025; 6(2): 46.     CrossRef
  • Advances in the computational development of hepatitis B virus capsid assembly modulators
    Ke Liu, Shaoqing Du, Weiqiao Deng, Zongjin Qu, Xueping Hu
    Drug Discovery Today.2025; 30(10): 104458.     CrossRef
  • Core protein inhibitors: Opportunities and challenges at the forefront of hepatitis B cure: Editorial on “Phase 1 trial of the safety, pharmacokinetics, and antiviral activity of EDP-514 in untreated viremic chronic hepatitis B patients”
    Hae Lim Lee, Jeong Won Jang
    Clinical and Molecular Hepatology.2024; 30(4): 692.     CrossRef
  • 10,348 View
  • 169 Download
  • 5 Web of Science
  • Crossref

Viral hepatitis

Efficacy, safety, and pharmacokinetics of capsid assembly modulator linvencorvir plus standard of care in chronic hepatitis B patients
Jinlin Hou, Edward Gane, Rozalina Balabanska, Wenhong Zhang, Jiming Zhang, Tien Huey Lim, Qing Xie, Chau-Ting Yeh, Sheng-Shun Yang, Xieer Liang, Piyawat Komolmit, Apinya Leerapun, Zenghui Xue, Ethan Chen, Yuchen Zhang, Qiaoqiao Xie, Ting-Tsung Chang, Tsung-Hui Hu, Seng Gee Lim, Wan-Long Chuang, Barbara Leggett, Qingyan Bo, Xue Zhou, Miriam Triyatni, Wen Zhang, Man-Fung Yuen
Clin Mol Hepatol 2024;30(2):191-205.
Published online January 8, 2024
DOI: https://doi.org/10.3350/cmh.2023.0422
Background/Aims
Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients.
Methods
This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks.
Results
68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported.
Conclusions
48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.

Citations

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  • Current status and challenges of therapeutic targets, novel drugs and delivery systems for hepatitis B: how far to our goal?
    Yanmei Liao, Fei Lv, Mei Zhou, Jie Shen, Tianwen Quan
    Frontiers in Cellular and Infection Microbiology.2026;[Epub]     CrossRef
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    Chunting Zhu, Jie Yang, Yu Sheng, Min Fang
    Frontiers in Immunology.2026;[Epub]     CrossRef
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    Zihan Jin, Libo Tang, Yuhao Wang, Shihong Zhong, Yongyin Li
    Clinical and Molecular Hepatology.2026; 32(3): e427.     CrossRef
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    Tatsuo Kanda, Reina Sasaki-Tanaka, Atsunori Tsuchiya, Shuji Terai
    World Journal of Hepatology.2025;[Epub]     CrossRef
  • Functional Cure for Hepatitis B Virus: Challenges and Achievements
    Oren Shechter, Daniel G. Sausen, Harel Dahari, Andrew Vaillant, Scott J. Cotler, Ronen Borenstein
    International Journal of Molecular Sciences.2025; 26(8): 3633.     CrossRef
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    Ke Liu, Shaoqing Du, Weiqiao Deng, Zongjin Qu, Xueping Hu
    Drug Discovery Today.2025; 30(10): 104458.     CrossRef
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    Yujia Zhu, Hongxiao Song, Fengchao Xu, Mian Huang, Guangyun Tan
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    Minghui Liang, Yutong Dou, Jian Zhang, Zechun Yang, Yuanyuan Liu, Mei Wang, Yiyan Mao, Lindan Guan, Aixin Li, Yuqing Cai, Yan Wang, Peng Xue, Lei Zhang, Zhuanchang Wu, Xinyong Liu, Peng Zhan, Haiyong Jia
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    Jiwon Yang, Jonggi Choi
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    Mehrangiz Dezhbord, Seong Ho Kim, Soree Park, Da Rae Lee, Nayeon Kim, Juhee Won, Ah Ram Lee, Dong-Sik Kim, Kyun-Hwan Kim
    Clinical and Molecular Hepatology.2024; 30(3): 539.     CrossRef
  • Novel mechanistic insights – A brand new Era for anti-HBV drugs
    Weiping Lyu, Haoming Qin, Qi Li, Dehua Lu, Cheng Shi, Kangchen Zhao, Shengran Zhang, Ruohan Yu, Huiying Zhang, Xiaonan Zhou, Sitian Xia, Liangren Zhang, Xiaoqian Wang, Xiaowei Chi, Zhenming Liu
    European Journal of Medicinal Chemistry.2024; 279: 116854.     CrossRef
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  • 272 Download
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Viral hepatitis

Hepatitis B core-related antigen dynamics and risk of subsequent clinical relapses after nucleos(t)ide analog cessation
Ying-Nan Tsai, Jia-Ling Wu, Cheng-Hao Tseng, Tzu-Haw Chen, Yi-Ling Wu, Chieh-Chang Chen, Yu-Jen Fang, Tzeng-Huey Yang, Mindie H. Nguyen, Jaw-Town Lin, Yao-Chun Hsu
Clin Mol Hepatol 2024;30(1):98-108.
Published online December 14, 2023
DOI: https://doi.org/10.3350/cmh.2023.0194
Background/Aims
Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB), but biomarkers for post-treatment monitoring are limited. We investigated whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR).
Methods
This retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase > two times the upper limit of normal with recurrent viremia. We applied time-dependent Cox proportional hazard models to clarify the association between HBcrAg levels and subsequent CR.
Results
The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.6% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5–40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7–67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1–62.4%). Time-varying HBcrAg level was a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.53 per log U/mL; 95% CI, 1.12–2.08) with adjustment for EOT HBsAg, EOT anti-HBe, EOT HBcrAg and time-varying HBsAg. During follow-up, HBcrAg <1,000 U/mL predicted a lower risk of CR (aHR, 0.41; 95% CI, 0.21–0.81).
Conclusions
Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be useful to guide post-treatment monitoring.

Citations

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  • Novel HBV Biomarkers-Guided NAs Withdrawal Strategy Promotes HBsAg Clearance in Asian CHB Patients: A Randomized Controlled Trial
    Rong Fan, Rui Deng, Qing Xie, Fang Wang, Xieer Liang, Hong Ma, Huiying Rao, Yanhang Gao, Chunxiu Zhong, Qing Guo, Sheng Shen, Ya Xu, Xingyu Lu, Hongbo Gao, Honglian Bai, Xiaoguang Dou, Jian Sun
    Clinical Gastroenterology and Hepatology.2026; 24(6): 1611.     CrossRef
  • Similar hepatic outcome by SGLT2i vs. DPP4i for at-risk cohort with CHB & T2DM: A nationwide target trial emulation study
    Byungyoon Yun, Juyeon Oh, Heejoo Park, Jian Lee, Beom Kyung Kim, Jin-Ha Yoon
    Annals of Hepatology.2026; 31(1): 102175.     CrossRef
  • Mitochondrial metabolic remodeling predicts therapeutic response to PegIFN-α in chronic hepatitis B
    Yingying Zhang, Xiu Han, Chengyu Xu, Yahui Song, Jinghan Zhu, Ruoran Zhou, Yiling Chen, Mingming Liu, Junchi Xu, Xiangwei Wu, Qingzhen Han, Zutao Chen
    Frontiers in Cellular and Infection Microbiology.2026;[Epub]     CrossRef
  • Risk factors and predicted model for clinical relapse after antiviral therapy cessation in chronic hepatitis B patients: a retrospective real-world data analysis
    Xiaoli Zhang, Meiyan Mao, Yunxia Zhang, Xiuxi Li
    BioMedical Engineering OnLine.2026;[Epub]     CrossRef
  • Clinical utility of hepatitis B core-related antigen in chronic hepatitis B infection: diagnostic, prognostic, and therapeutic implications
    Bukhari Isah Shuaib, Usman Linda Itunu, Aminat Daud
    Egyptian Liver Journal.2026;[Epub]     CrossRef
  • Dynamics of Circulatory HBcrAg and HBsAg After Nucleos(t)ide Analogue Cessation Using iTACT Assays to Predict Clinical Flares and HBsAg Loss
    Ying‐Nan Tsai, Jia‐Ling Wu, Cheng‐Hao Tseng, Tzu‐Haw Chen, Ying‐Chu Chung, Mindie H. Nguyen, Jaw‐Town Lin, Katsuya Nagaoka, Yasuhito Tanaka, Yao‐Chun Hsu
    Alimentary Pharmacology & Therapeutics.2026; 64(1): 89.     CrossRef
  • Low-level hepatitis B surface antigen by ECLIA stratifies early relapse risk in patients with interferon-based HBV functional cure
    Xiangyong Li, Baoer Wu, Huaping Xie, Hao Hu, Ting Liu, Xu You, Yanhua Bi, Yurong Gu
    Frontiers in Immunology.2026;[Epub]     CrossRef
  • Hepatitis B core-related antigen as a multifaceted biomarker in chronic hepatitis B: implications for immune activity and hepatocellular carcinoma prediction
    Kwon Yong Tak, Seok Hwan Kim, Myeong Jun Song
    The Korean Journal of Internal Medicine.2026; 41(4): 636.     CrossRef
  • Early HBcrAg and Anti‐HBc Levels Identify Patients at High Risk for Severe Flares After Nucleos(t)ide Analogue Cessation—A Pooled Analysis of Two Clinical Trials
    Edo J. Dongelmans, Jordan J. Feld, André Boonstra, Sylvia M. Brakenhoff, David Wong, Colina Yim, Mark Claassen, Pieter Honkoop, Bettina E. Hansen, Robert A. de Man, Scott Fung, Thomas Berg, Florian van Bömmel, Harry L. A. Janssen, Milan J. Sonneveld
    Alimentary Pharmacology & Therapeutics.2025; 61(3): 570.     CrossRef
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    Jiarui Zheng, Zilong Wang, Linxiang Huang, Zixuan Qiu, Yandi Xie, Suzhen Jiang, Bo Feng
    Virus Research.2025; 351: 199507.     CrossRef
  • Hepatitis B core-related antigen as a promising serological marker for monitoring hepatitis B virus cure
    Yue Qiu, Qiao Tang, Xiao-Qing Liu, Yun-Ling Xue, Yi Zeng, Peng Hu
    World Journal of Hepatology.2025;[Epub]     CrossRef
  • Comparative Hepatic Outcomes of SGLT2i or DPP4i Compared to GLP‐1RA in CHB and T2DM Patients
    Byungyoon Yun, Juyeon Oh, Heejoo Park, Jian Lee, Beom Kyung Kim, Jin‐Ha Yoon
    Liver International.2025;[Epub]     CrossRef
  • Discontinuation of nucleos(t)ide analogues after NA-induced HBsAg seroclearance: a single-center 48-week retrospective study
    Yong-Hong Wang, Ya-Chao Tao, Meng-Lan Wang, Cheng-Run Song, Jiang-Nan Peng, En-Qiang Chen
    Journal of Virus Eradication.2025; 11(4): 100617.     CrossRef
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    Yoshihiko Yano, Itsuko Sato, Takamitsu Imanishi, Ryutaro Yoshida, Takanori Matsuura, Yoshihide Ueda, Yuzo Kodama
    Diagnostics.2024; 14(7): 728.     CrossRef
  • Letter regarding “Hepatitis B core-related antigen dynamics and risk of subsequent clinical relapses after nucleos(t)ide analog cessation”
    Yun-Fan Liaw
    Clinical and Molecular Hepatology.2024; 30(2): 269.     CrossRef
  • Enhancing off-nucleos(t)ide analogue outcome predictions in chronic hepatitis B with time-varying hepatitis B core-related antigen
    Chen-Te Huang, Tai-Chung Tseng
    Clinical and Molecular Hepatology.2024; 30(2): 154.     CrossRef
  • Optimizing off-treatment outcome predictions: The potential of time-varying HBcrAg and the need for more research
    Ying-Nan Tsai, Jia-Ling Wu, Yao-Chun Hsu
    Clinical and Molecular Hepatology.2024; 30(2): 276.     CrossRef
  • Harnessing hepatitis B core-related antigen measurement to optimize posttreatment monitoring
    Ying-Nan Tsai, Jia-Ling Wu, Yao-Chun Hsu
    Clinical and Molecular Hepatology.2024; 30(2): 293.     CrossRef
  • A critical review of diagnostic and prognostic markers of chronic hepatitis B infection
    Shuaibu Abdullahi Hudu, Sa’adatu Haruna Shinkafi, Abdulgafar Olayiwola Jimoh
    Medical Review.2024; 4(3): 225.     CrossRef
  • Virological markers for clinical trials in chronic viral hepatitis
    Jean-Michel Pawlotsky
    JHEP Reports.2024; 6(11): 101214.     CrossRef
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Viral hepatitis

Prognostic role of computed tomography analysis using deep learning algorithm in patients with chronic hepatitis B viral infection
Jeongin Yoo, Heejin Cho, Dong Ho Lee, Eun Ju Cho, Ijin Joo, Sun Kyung Jeon
Clin Mol Hepatol 2023;29(4):1029-1042.
Published online August 29, 2023
DOI: https://doi.org/10.3350/cmh.2023.0190
Background/Aims
The prediction of clinical outcomes in patients with chronic hepatitis B (CHB) is paramount for effective management. This study aimed to evaluate the prognostic value of computed tomography (CT) analysis using deep learning algorithms in patients with CHB. Methods: This retrospective study included 2,169 patients with CHB without hepatic decompensation who underwent contrast-enhanced abdominal CT for hepatocellular carcinoma (HCC) surveillance between January 2005 and June 2016. Liver and spleen volumes and body composition measurements including subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and skeletal muscle indices were acquired from CT images using deep learning-based fully automated organ segmentation algorithms. We assessed the significant predictors of HCC, hepatic decompensation, diabetes mellitus (DM), and overall survival (OS) using Cox proportional hazard analyses. Results: During a median follow-up period of 103.0 months, HCC (n=134, 6.2%), hepatic decompensation (n=103, 4.7%), DM (n=432, 19.9%), and death (n=120, 5.5%) occurred. According to the multivariate analysis, standardized spleen volume significantly predicted HCC development (hazard ratio [HR]=1.01, P=0.025), along with age, sex, albumin and platelet count. Standardized spleen volume (HR=1.01, P<0.001) and VAT index (HR=0.98, P=0.004) were significantly associated with hepatic decompensation along with age and albumin. Furthermore, VAT index (HR=1.01, P=0.001) and standardized spleen volume (HR=1.01, P=0.001) were significant predictors for DM, along with sex, age, and albumin. SAT index (HR=0.99, P=0.004) was significantly associated with OS, along with age, albumin, and MELD. Conclusions: Deep learning-based automatically measured spleen volume, VAT, and SAT indices may provide various prognostic information in patients with CHB.

Citations

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    Xiaoqian Xu, Hong You, Jidong Jia, Yuanyuan Kong
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    Yong Eun Chung
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Letter to the Editor

Viral hepatitis

Dear Editor, I read with great interest the editorial paper by Oh and Sinn [1] entitled “Is liver biopsy mandatory to identify immunetolerant phase of chronic hepatitis B?” published online ahead of print. In their paper, Oh and Sinn [1] suggested that the status of patients presumed to be in the immune-tolerant phase without histological information should be carefully evaluated. I would like to draw attention to the following printing error related to the normal serum alanine aminotransferase (ALT) levels according to the American Association for the Study of Liver Disease (AASLD) guidelines. The recommended normal serum ALT level for males was incorrectly written as “<33 U/L” in both the text and Table 1. However, according to the AASLD 2018 hepatitis B guidance [2], the upper limit of normal for ALT in males is 35 U/L. I believe that correcting this printing error will prevent any possible confusion in daily practice guiding management decisions.
  • 6,320 View
  • 34 Download
  • 1 Web of Science

Review

Hepatic neoplasm

Overview of Asian clinical practice guidelines for the management of hepatocellular carcinoma: An Asian perspective comparison
Yuri Cho, Bo Hyun Kim, Joong-Won Park
Clin Mol Hepatol 2023;29(2):252-262.
Published online March 10, 2023
DOI: https://doi.org/10.3350/cmh.2023.0099
Hepatocellular carcinoma (HCC) is highly prevalent and the third most common cause of cancer-related death in Asia. In contrast to the West, the main etiology of HCC in many Asian countries except Japan is chronic hepatitis B virus infection. Differences in the major causes of HCC lead to significant clinical and treatment differences. This review summarizes and compares guidelines on managing HCC from China, Hong Kong, Taiwan, Japan, and South Korea. From oncology and socio-economic perspectives, factors such as underlying diseases, staging methods, government policies, insurance coverage, and medical resources contribute to varying treatment strategies among countries. Furthermore, the differences in each guideline are fundamentally caused by the lack of incontrovertible medical evidence, and even existing results of clinical trials can be interpreted differently. This review will provide a complete overview of the current Asian guidelines for HCC in recommendations and in practice.

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Correspondence

Viral hepatitis

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Review

Viral hepatitis

Development of hepatocellular carcinoma in treated and untreated patients with chronic hepatitis B virus infection
Chih-Lin Lin, Jia-Horng Kao
Clin Mol Hepatol 2023;29(3):605-622.
Published online February 15, 2023
DOI: https://doi.org/10.3350/cmh.2022.0342
Hepatitis B virus (HBV) is responsible for more than 50% of hepatocellular carcinoma (HCC) in HBV hyperendemic areas, such as the Asia-Pacific region. Several hepatitis B viral factors are involved in HBV-related hepatocarcinogenesis. Hepatitis B viral load is the most important risk factor of HCC development. In addition, HBV integration, HBV genotype C, and core-promoter mutations are also associated with a risk of HCC development. For untreated chronic hepatitis B (CHB) patients, the estimated HCC incidence rates per 100 patient-years were 0.03–0.17 in inactive carriers, 0.07–0.42 in asymptomatic carriers, 0.12–0.49 in chronic hepatitis, and 2.03–3.37 in cirrhosis. Complementary to HBV DNA, serum levels of the hepatitis B surface antigen and hepatitis B core-related antigen (HBcrAg) can predict the occurrence of HCC for untreated patients with low and intermediate viral loads, respectively. For patients receiving antiviral therapy, the risks of HCC occurrence 40–60% lower than those for untreated patients. Patients treated with residual detectable HBV DNA or intrahepatic cccDNA still have a risk of HCC. Serum levels of HBcrAg, M2BPGi and fibrosis-4 are predictive of the risk of HCC development in treated patients. Several well-developed HCC risk scores can help clinicians identify high-risk CHB patients for HCC surveillance, regardless of treatment status. These strategies can help minimize the threat of HCC and prolong survival in CHB patients.

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Letter to the Editor

Viral hepatitis

Citations

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  • Correspondence on Letter regarding “Long-term prognosis and the need for histologic assessment of chronic hepatitis B in the serological immune tolerant phase”
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  • 7,275 View
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Review

Viral hepatitis

The role of different viral biomarkers on the management of chronic hepatitis B
Lung-Yi Mak, Rex Wan-Hin Hui, James Fung, Wai Kay Seto, Man-Fung Yuen
Clin Mol Hepatol 2023;29(2):263-276.
Published online January 19, 2023
DOI: https://doi.org/10.3350/cmh.2022.0448
Chronic hepatitis B infection is a major public health challenge. With the advancement in technology, various components of the viral cycle can now be measured in the blood to assess viral activity. In this review article, we summarize the relevant data of how antiviral therapies impact viral biomarkers, and discuss their potential implications. Viral nucleic acids including hepatitis B virus (HBV) double-stranded deoxy-ribonucleic acid (DNA) and to a lesser extent, pre-genomic RNA, are readily suppressed by nucleos(t)ide analogues (NUCs). The primary role of these markers include risk prediction for hepatocellular carcinoma (HCC) and risk stratification for partial cure, defined as off-therapy virological control, or functional cure, defined as hepatitis B surface antigen (HBsAg) seroclearance plus undetectable serum HBV DNA for ≥6 months. Viral translational products including hepatitis e antigen, quantitative HBsAg and hepatitis B core-related antigen can be reduced by NUCs and pegylated interferon a. They are important in defining disease phase, delineating treatment endpoints, and predicting clinical outcomes including HCC risk and partial/ functional cure. As the primary outcome of phase III trials in chronic hepatitis B is set as HBsAg seroclearance, appropriate viral biomarkers can potentially inform the efficacy of novel compounds. Early viral biomarker response can help with prioritization of subjects into clinical trials. However, standardization and validation studies would be crucial before viral biomarkers can be broadly implemented in clinical use.

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Correspondence

Hepatic neoplasm

Citations

Citations to this article as recorded by  Crossref logo
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