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"Chronic hepatitis B"

Reviews

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.
  • 1,049 View
  • 175 Download
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

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  • 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
  • 4,155 View
  • 204 Download
  • Crossref

Reply to Correspondence

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
  • 3,567 View
  • 25 Download

Correspondences

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

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
  • 2,806 View
  • 10 Download
  • Crossref
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
  • 2,171 View
  • 11 Download

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
  • 8,019 View
  • 70 Download

Editorials

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

Citations

Citations to this article as recorded by  Crossref logo
  • 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
  • 2,667 View
  • 44 Download
  • 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
Clin Mol Hepatol 2026;32(1):423-425.
Published online April 11, 2025
DOI: https://doi.org/10.3350/cmh.2025.0369

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
  • 4,190 View
  • 39 Download
  • Crossref

Original Articles

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
  • 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
  • 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
  • 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.2025;[Epub]     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
  • 11,923 View
  • 209 Download
  • 12 Web of Science
  • 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

Citations to this article as recorded by  Crossref logo
  • 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
  • Correspondence to editorial 2 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): e62.     CrossRef
  • Correspondence to editorial 3 on “Baveno VI-SSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis”
    Haiyu Wang, Jinjun Chen
    Clinical and Molecular Hepatology.2026; 32(1): e65.     CrossRef
  • Reply to correspondence on “Baveno VI-SSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis”
    Mathias Jachs, Mattias Mandorfer
    Clinical and Molecular Hepatology.2026; 32(1): e106.     CrossRef
  • Ammonia‐to‐Urea Ratio: A Noninvasive First‐Line Tool for Detecting Clinically Significant Portal Hypertension
    Hatime Ouahbi, Vincent Haghnejad, Alexia Audouy, Maël Silva Rodriguez, Françoise Barbé, Jean‐Louis Guéant, Jean‐Pierre Bronowicki, Abderrahim Oussalah
    JGH Open.2025;[Epub]     CrossRef
  • 9,766 View
  • 208 Download
  • 8 Web of Science
  • Crossref

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.

Citations

Citations to this article as recorded by  Crossref logo
  • Correspondence to editorial on “Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial”
    Hyung Joon Yim, Seong Hee Kang, Young Kul Jung, Jin Mo Yang
    Clinical and Molecular Hepatology.2026; 32(1): e55.     CrossRef
  • Residual viral expression in siRNA-treated HBV-replicating cell and mouse models
    Mingzhu Xu, Yuyan Qian, Ziyang Song, Haiyu Wang, Lei Yue, Jiangxia Liu, Yaming Li, Wenjing Zai, Zhenghong Yuan, Jieliang Chen
    Antiviral Research.2025; 240: 106210.     CrossRef
  • Anti-HBV treatment partially restores the dysfunction of innate immune cells and unconventional T cells during chronic HBV infection
    Yiwen Shu, Sumeng Li, Yanqin Du, Xin Zheng
    Frontiers in Immunology.2025;[Epub]     CrossRef
  • Quantitatively Evaluate the Improvement of Functional Cure for the Quality of Life of Chronic Hepatitis B Cases: Evidence from a Cross-Sectional Study in China
    Sihui Zhang, Zhiliang Gao, Hui Li, Yi Kang, Lei Fu, Xuebing Chen, Xiaoyuan Xu, Xinyue Chen, Hui Zhuang, Hui Zheng, Fuqiang Cui
    Healthcare.2025; 13(20): 2590.     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
  • An RNA interference therapeutic potentially achieves functional cure of chronic hepatitis B virus infection
    Ze-Ao Huang, Yang Yang, Shuo Yang, Guang-Shen Ji, Rui Fu, Zhi-Kang Tian, Yu-Cheng Wu, Geng-Shen Song
    Nature Communications.2025;[Epub]     CrossRef
  • A Study on Serum Protein Tracking in Patients with Low Levels of HBsAg Undergoing Treatment for Chronic Hepatitis B with a Combination of Tenofovir Disoproxil Fumarate and Pegylated Interferon
    Yimin Chen, Min Deng, Mingkai Tong, Peixia Lin, Hua Xuan, Dahai Wei
    Hepatitis Monthly.2025;[Epub]     CrossRef
  • Machine learning model for HBsAg seroclearance after 48-week pegylated interferon therapy in inactive HBsAg carriers: a retrospective study
    Jianxia Dong, Shan Ren, Jing Zhao, Pengxuan Wu, Haitian Yu, Yao Xie, Junliang Fu, Xiaorong Mao, Zhiliang Gao, Bingliang Lin, Qingfa Ruan, Yongfang Jiang, Xiulan Xue, Yueyong Zhu, Haidong Zhao, Haifang Cao, Xinyue Chen, Sujun Zheng
    Virology Journal.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
  • 14,348 View
  • 583 Download
  • 10 Web of Science
  • Crossref

Correspondence

Viral hepatitis

Expanding treatment eligibility for chronic hepatitis B: Balancing benefits, limitations, and healthcare access: Correspondence to editorial on “Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TORCH-B trial”
Yao-Chun Hsu, Chi-Yi Chen, Jaw-Town Lin
Clin Mol Hepatol 2025;31(2):e169-e172.
Published online December 23, 2024
DOI: https://doi.org/10.3350/cmh.2024.1138
  • 5,655 View
  • 31 Download

Letter to the Editor

Viral hepatitis

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

Citations

Citations to this article as recorded by  Crossref logo
  • 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
  • 6,078 View
  • 37 Download
  • 1 Web of Science
  • Crossref

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

Citations to this article as recorded by  Crossref logo
  • Large-scale profile study on hepatitis B surface antigen levels in chronic hepatitis B: implications for drug development targeting functional cure
    Rex Wan-Hin Hui, Trevor Kwan-Hung Wu, Karen Cheuk-Ying Ho, Ryan Hin-Man Leung, Matthew Shing-Hin Chung, Danny Ka-Ho Wong, James Fung, Wai-Kay Seto, Lung Yi Mak, Man-Fung Yuen
    Gut.2026; 75(1): 119.     CrossRef
  • Correspondence to editorial on “Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial”
    Hyung Joon Yim, Seong Hee Kang, Young Kul Jung, Jin Mo Yang
    Clinical and Molecular Hepatology.2026; 32(1): e55.     CrossRef
  • Viral manipulation of host cell glutamine metabolism and glutamine rewiring in hepatic diseases: Editorial on “Glutamate dehydrogenase 1-dependent α-ketoglutarate promotes hepatitis B virus transcription by modulating histone methylations on the covalentl
    Mehrangiz Dezhbord, Kyun-Hwan Kim
    Clinical and Molecular Hepatology.2026; 32(1): 385.     CrossRef
  • 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
    Clinical and Molecular Hepatology.2026; 32(1): 184.     CrossRef
  • Large-scale screening of HBV epitopes restricted by multiple prevalent HLA-B/C allotypes and routine detection of HBV-specific T cells in CHB patients
    Yandan Wu, Yu Zhao, Ruixue Ji, Pinqing Li, Huijuan Chen, Fangping Yue, Yi Wu, Jie Qiu, Chuanlai Shen
    Frontiers in Immunology.2026;[Epub]     CrossRef
  • Reply to: “ALT to qHBsAg ratio predicts HBsAg seroclearance in HBeAg-negative patients receiving Peg-IFNα based therapy”
    Rex Wan-Hin Hui, Lung-Yi Mak, Man-Fung Yuen
    Journal of Hepatology.2025; 82(5): e228.     CrossRef
  • Expanding treatment indications in chronic hepatitis B: Should we treat all patients?
    Rex Wan-Hin Hui, Lung-Yi Mak, James Fung, Wai-Kay Seto, Man-Fung Yuen
    Hepatology International.2025; 19(2): 304.     CrossRef
  • Combining therapeutic agents to target the immune systems of hepatitis B patients: what do we need to consider?
    Shang-Chin Huang, Jia-Horng Kao
    Expert Review of Gastroenterology & Hepatology.2025; 19(4): 371.     CrossRef
  • Efficacy of Antiviral Therapy in Chronic Hepatitis B Patients With Normal Alanine Aminotransferase: A Systematic Review and Meta‐Analysis
    Yuting Diao, Yueying Zeng, Zhihao Huang, Chunfang You, Kevork M. Peltekian
    Canadian Journal of Gastroenterology and Hepatology.2025;[Epub]     CrossRef
  • Hepatitis B: Neue therapeutische Ansätze für eine funktionelle Heilung
    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
  • 9,867 View
  • 489 Download
  • 12 Web of Science
  • Crossref

Reply to Correspondence

Viral hepatitis

Reply to correspondence on “Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using vibration-controlled transient elastography: Systematic review and meta-analysis”
Mirko Zoncapè, Emmanuel A. Tsochatzis
Clin Mol Hepatol 2025;31(1):e117-e118.
Published online November 11, 2024
DOI: https://doi.org/10.3350/cmh.2024.0994
  • 4,987 View
  • 26 Download

Editorial

Viral hepatitis

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

Citations

Citations to this article as recorded by  Crossref logo
  • 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
  • 5,524 View
  • 32 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
  • 5,765 View
  • 41 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.
  • 6,790 View
  • 189 Download
  • 5 Web of Science

Correspondence

Viral hepatitis

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

Citations

Citations to this article as recorded by  Crossref logo
  • 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
  • 5,041 View
  • 30 Download
  • 1 Web of Science
  • Crossref

Editorial

Viral hepatitis

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

Citations

Citations to this article as recorded by  Crossref logo
  • 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
  • 6,827 View
  • 60 Download
  • 3 Web of Science
  • Crossref

Letter to the Editor

Viral hepatitis

Presence of liver fibrosis in chronic hepatitis B patients with varying serum hepatitis B virus DNA levels: Letter to the editor on “Non-linear association between liver fibrosis scores and viral load in patients with chronic hepatitis B”
Jian Wang, Shaoqiu Zhang, Chuanwu Zhu, Yuanwang Qiu, Chao Wu, Rui Huang
Clin Mol Hepatol 2025;31(1):e27-e30.
Published online August 7, 2024
DOI: https://doi.org/10.3350/cmh.2024.0602

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
  • 6,564 View
  • 65 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
  • 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
  • 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.2025;[Epub]     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
  • 5,914 View
  • 130 Download
  • 6 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

Citations to this article as recorded by  Crossref logo
  • 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
  • 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
  • The Evolving Application of Ultrasound in the Precision Management of Small Hepatocellular Carcinoma
    Xin Guan, Xinyuan Hu, Hong Han, Dezhi Zhang, Huixiong Xu
    Advanced Ultrasound in Diagnosis and Therapy.2025; 9(4): 375.     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.2025;[Epub]     CrossRef
  • Transient Elastography and Fibroscan: Stethoscope of a Hepatologist in Today’s World
    Sajid Jalil, Mangesh Pagadala, Nicholas Dunn, Hanna Blaney, Mohamed Elfeki, Nimish Thakral, Ashwani K. Singal
    Current Hepatology Reports.2025;[Epub]     CrossRef
  • 6,351 View
  • 139 Download
  • 11 Web of Science
  • Crossref

Editorial

Viral hepatitis

Nucleos(t)ide analog therapy of chronic hepatitis B and extrahepatic cancer risk: Is tenofovir better than entecavir?: Editorial on “Extrahepatic malignancies and antiviral drugs for chronic hepatitis B: A nationwide cohort study”
Yewan Park, Dong Hyun Sinn
Clin Mol Hepatol 2024;30(4):718-720.
Published online July 8, 2024
DOI: https://doi.org/10.3350/cmh.2024.0519
  • 4,050 View
  • 76 Download

Reply to Correspondence

Viral hepatitis

Reply to correspondence on “Cardiovascular risk in chronic hepatitis B patients treated with tenofovir disoproxil fumarate or tenofovir alafenamide”
Pin-Nan Cheng, Ming-Lung Yu
Clin Mol Hepatol 2024;30(4):1031-1032.
Published online April 11, 2024
DOI: https://doi.org/10.3350/cmh.2024.0228
  • 5,107 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
  • 5,257 View
  • 47 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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  • 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
  • Mise à jour concernant le traitement des hépatites virales
    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
  • 7,935 View
  • 157 Download
  • 3 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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  • Hepatitis B virus infection and its treatment in Eastern Ethiopia
    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
  • 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
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    Yujia Zhu, Hongxiao Song, Fengchao Xu, Mian Huang, Guangyun Tan
    Frontiers in Immunology.2025;[Epub]     CrossRef
  • Multisite Occupancy and Multidimensional Optimization: Design and Evaluation of Piperazine-Thioureidobenzamide Derivatives as Potent HBV Capsid Assembly Modulators
    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
    Journal of Medicinal Chemistry.2025; 68(22): 24358.     CrossRef
  • Linvencovir: Paving the way for functional cure in hepatitis B
    Jiwon Yang, Jonggi Choi
    Clinical and Molecular Hepatology.2024; 30(2): 164.     CrossRef
  • Novel role of MHC class II transactivator in hepatitis B virus replication and viral counteraction
    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
  • 9,188 View
  • 256 Download
  • 7 Web of Science
  • Crossref

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

Citations to this article as recorded by  Crossref logo
  • 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
  • Achieving chronic hepatitis B functional cure: Factors and potential mechanisms
    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
  • 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.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
  • 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.2025; : 102175.     CrossRef
  • Clinical Significance and Remaining Issues of Anti-HBc Antibody and HBV Core-Related Antigen
    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
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    Jean-Michel Pawlotsky
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  • 6,839 View
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  • 9 Web of Science
  • Crossref

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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  • Reply to: “A machine learning model to predict liver-related outcomes after the functional cure of chronic hepatitis B: Is cirrhosis driving the performance?”
    Moon Haeng Hur, Jeong-Hoon Lee
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    Abdominal Radiology.2025;[Epub]     CrossRef
  • Correspondence to editorial on “Hepatocellular carcinoma prediction model performance decreases with long-term antiviral therapy in chronic hepatitis B patients”
    Xiaoqian Xu, Hong You, Jidong Jia, Yuanyuan Kong
    Clinical and Molecular Hepatology.2024; 30(4): 994.     CrossRef
  • Deep learning assisted biomarker development in patients with chronic hepatitis B: Editorial on “Prognostic role of computed tomography analysis using deep learning algorithm in patients with chronic hepatitis B viral infection”
    Yong Eun Chung
    Clinical and Molecular Hepatology.2024; 30(4): 669.     CrossRef
  • Decreasing performance of HCC prediction models during antiviral therapy for hepatitis B: what else to keep in mind: Editorial on “Hepatocellular carcinoma prediction model performance decreases with long-term antiviral therapy in chronic hepatitis B pati
    Beom Kyung Kim
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    Bingyao Huang, Yi Gao, Lina Wu
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  • Crossref

Letter to the Editor

Viral hepatitis

Letter regarding “Is liver biopsy essential to identifying the immune tolerant phase of chronic hepatitis B?”
Halil Haldun Emiroglu
Clin Mol Hepatol 2023;29(3):812-812.
Published online May 8, 2023
DOI: https://doi.org/10.3350/cmh.2023.0132
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.
  • 5,591 View
  • 33 Download

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

Correspondence on Letter regarding “Long-term prognosis and the need for histologic assessment of chronic hepatitis B in the serological immune tolerant phase”
Jeong-Ju Yoo, Sang Gyune Kim
Clin Mol Hepatol 2023;29(2):513-515.
Published online February 15, 2023
DOI: https://doi.org/10.3350/cmh.2023.0044
  • 5,690 View
  • 58 Download

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

Letter regarding “Long-term prognosis and the need for histologic assessment of chronic hepatitis B in the serological immune-tolerant phase”
Chia-Ming Chu, Yun-Fan Liaw
Clin Mol Hepatol 2023;29(2):510-512.
Published online January 30, 2023
DOI: https://doi.org/10.3350/cmh.2023.0018

Citations

Citations to this article as recorded by  Crossref logo
  • Correspondence on Letter regarding “Long-term prognosis and the need for histologic assessment of chronic hepatitis B in the serological immune tolerant phase”
    Jeong-Ju Yoo, Sang Gyune Kim
    Clinical and Molecular Hepatology.2023; 29(2): 513.     CrossRef
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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.

Citations

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Original Articles

Viral hepatitis

Hepatitis B virus pre-genomic RNA and hepatitis B core-related antigen reductions at week 4 predict favourable hepatitis B surface antigen response upon long-term nucleos(t)ide analogue in chronic hepatitis B
Lung-Yi Mak, Danny Wong, Alison Kuchta, Martina Hilfiker, Aaron Hamilton, Ning Chow, XianHua Mao, Wai Kay Seto, Man-Fung Yuen
Clin Mol Hepatol 2023;29(1):146-162.
Published online August 19, 2022
DOI: https://doi.org/10.3350/cmh.2022.0172
Background/Aims
We investigated the dynamics of serum HBV pre-genomic RNA (pgRNA) and hepatitis B core-related antigen (HBcrAg) in patients receiving nucleos(t)ide analogues (NAs) and their predictability for favourable suppression of serum hepatitis B surface antigen (HBsAg).
Methods
Serum viral biomarkers were measured at baseline, weeks 4, 12, 24, 36, and 48 of treatment. Patients were followed up thereafter and serum HBsAg level was measured at end of follow-up (EOFU). Favourable HBsAg response (FHR) was defined as ≤100 IU/mL or HBsAg seroclearance upon EOFU.
Results
Twenty-eight hepatitis B e antigen (HBeAg)-positive and 36 HBeAg-negative patients (median, 38.2 years old; 71.9% male) were recruited with median follow-up duration of 17.1 years (interquartile range, 12.8–18.2). For the entire cohort, 22/64 (34.4%) achieved FHR. For HBeAg-positive patients, serum HBV pgRNA decline at week 4 was significantly greater for patients with FHR compared to non-FHR (5.49 vs. 4.32 log copies/mL, respectively; P=0.016). The area under the receiver-operating-characteristic curve (AUROC) for week 4 HBV pgRNA reduction to predict FHR in HBeAg-positive patients was 0.825 (95% confidence interval [CI], 0.661–0.989). For HBeAg-negative patients, instead of increase in serum HBcrAg in non-FHR patients, FHR patients had median reduction in HBcrAg at week 4 (increment of 1.75 vs. reduction of 2.98 log U/mL; P=0.023). The AUROC for week 4 change of HBcrAg to predict FHR in HBeAg-negative patients was 0.789 (95% CI, 0.596–0.982).
Conclusions
Early on-treatment changes of serum HBV pgRNA and HBcrAg at 4 weeks predict HBsAg seroclearance or ≤100 IU/mL in NA-treated CHB patients upon long-term FU.

Citations

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    Yue Qiu, Qiao Tang, Xiao-Qing Liu, Yun-Ling Xue, Yi Zeng, Peng Hu
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COVID-19 vaccine immunogenicity among chronic liver disease patients and liver transplant recipients: A meta-analysis
Ka Shing Cheung, Chiu Hang Mok, Xianhua Mao, Ruiqi Zhang, Ivan FN Hung, Wai Kay Seto, Man Fung Yuen
Clin Mol Hepatol 2022;28(4):890-911.
Published online June 3, 2022
DOI: https://doi.org/10.3350/cmh.2022.0087
Background/Aims
Data of coronavirus disease 2019 (COVID-19) vaccine immunogenicity among chronic liver disease (CLD) and liver transplant (LT) patients are conflicting. We performed meta-analysis to examine vaccine immunogenicity regarding etiology, cirrhosis status, vaccine platform and type of antibody.
Methods
We collected data via three databases from inception to February 16, 2022, and reported pooled seroconversion rate, T cell response and safety data after two vaccine doses.
Results
Twenty-eight (CLD only: 5; LT only: 18; both: 2; LT with third dose: 3) observational studies of 3,945 patients were included. For CLD patients, seroconversion rate ranged between 84% (95% confidence interval [CI], 76–90%) and 91% (95% CI, 83–95%), based predominantly on neutralizing antibody and anti-spike antibody, respectively. Seroconversion rate was 81% (95% CI, 76–86%) in chronic hepatitis B, 96% (95% CI, 93–97%) in non-alcoholic fatty liver disease, 85% (95% CI, 75–91%) in cirrhosis and 85% (95% CI, 78–90%) in non-cirrhosis, 86% (95% CI, 78–92%) for inactivated vaccine and 89% (95% CI, 71–96%) for mRNA vaccine. The pooled seroconversion rate of anti-spike antibody was 66% (95% CI, 55–75%) after two doses of mRNA vaccines and 88% (95% CI, 58–98%) after third dose among LT recipients. T cell response rate was 65% (95% CI, 30–89%). Prevalence of adverse events was 27% (95% CI, 18–38%) and 63% (95% CI, 39–82%) among CLD and LT groups, respectively.
Conclusions
CLD patients had good humoral response to COVID-19 vaccine, while LT recipients had lower response.

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Guideline

Viral hepatitis

KASL clinical practice guidelines for management of chronic hepatitis B
The Korean Association for the Study of the Liver (KASL)
Clin Mol Hepatol 2022;28(2):276-331.
Published online April 1, 2022
DOI: https://doi.org/10.3350/cmh.2022.0084

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Original Article

Viral hepatitis

Tenofovir alafenamide treatment may not worsen the lipid profile of chronic hepatitis B patients: A propensity score-matched analysis
Joonho Jeong, Jung Woo Shin, Seok Won Jung, Eun Ji Park, Neung Hwa Park
Clin Mol Hepatol 2022;28(2):254-264.
Published online December 28, 2021
DOI: https://doi.org/10.3350/cmh.2021.0314
Background/Aims
Tenofovir alafenamide (TAF) has shown less favorable effect on lipids compared to tenofovir disoproxil fumarate (TDF) in clinical trials. However, data regarding these outcomes in patients with chronic hepatitis B (CHB) are scarce. Therefore, this study aimed to evaluate the effect of TAF on the lipid in patients with CHB.
Methods
A total of 237 TAF-treated CHB patients compared with TDF, inactive CHB, and non-hepatitis B virus (HBV)-infected control groups using propensity score matching (PSM).
Results
Following PSM, each analysis was conducted on cohorts via the matching of 70:140 (TAF:TDF), 89:89 (TAF:inactive CHB), 140:560 (TAF:non-HBV infected control), and 368:1,472 (TDF:non-HBV-infected control). A significant decrease in the total cholesterol (TC) level was noted at 48 weeks in the TDF group compared to the TAF group (176.3±32.9 vs. 156.7±27.7, P<0.001) and the non-HBV-infected control group (175.0±29.5 vs. 156.2±28.3, P<0.001). However, no significant change in TC was observed in the TAF group and inactive CHB or non-HBV-infected control groups at 48 weeks. For the subgroup analyses of TAF vs. non-HBV-infected control subjects and inactive CHB patients whose detailed lipid profile information were available, no between-group differences in TC, low-density lipoprotein (LDL)-cholesterol, highdensity lipoprotein (HDL)-cholesterol, TC/HDL ratio, and LDL/HDL ratio were observed at 48 weeks.
Conclusions
TDF seems to have a lipid-lowering effect compared to the non-HBV-infected control and TAF-treated groups. However, in real practice, TAF might not worsen the lipid profiles of subjects compared to non-HBV-infected controls and patients with inactive CHB.

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Review

The best predictive model for hepatocellular carcinoma in patients with chronic hepatitis B infection
Jung Hwan Yu, Soon Gu Cho, Young-Joo Jin, Jin-Woo Lee
Clin Mol Hepatol 2022;28(3):351-361.
Published online November 26, 2021
DOI: https://doi.org/10.3350/cmh.2021.0281
Chronic hepatitis B (CHB) seriously threatens human health. About 820,000 deaths annually are due to related complications such as hepatitis B and hepatocellular carcinoma (HCC). Recently, the use of oral antiviral agents has significantly improved the prognosis of patients with CHB infection and reduced the risk of HCC. However, hepatitis B virus still remains a major factor in the development of HCC, raising many concerns. Therefore, numerous studies have been conducted to assess the risk of HCC in patients with CHB infection and many models have been proposed to predict the risk of developing HCC. However, as each study has different models for predicting HCC development that can be applied depending on the use of antiviral agents or the type of antiviral agents, it is necessary to properly understand characteristics of each model when using it for the evaluation of HCC in patients with CHB infection. In addition, because different variables such as host factor, viral activity, and cirrhosis are used to evaluate the risk of HCC development, it is necessary to assess the risk by carefully verifying which variables are used. Recently, studies have also evaluated the risk of HCC using risk prediction models through transient elastography and artificial intelligence (AI) system. These HCC risk predication models are also noteworthy. In this review, we aimed to compare HCC risk prediction models in patients with CHB infection reported to date to confirm variables used and specificity between each model to determine an appropriate HCC risk prediction method.

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Editorial

Viral hepatitis

Is tenofovir and entecavir combination therapy still the optimal treatment for chronic hepatitis B patients with prior suboptimal response?
Byoung Kuk Jang
Clin Mol Hepatol 2020;26(3):312-314.
Published online July 1, 2020
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Review

Viral hepatitis

KASL clinical practice guidelines for management of chronic hepatitis B
Korean Association for the Study of the Liver (KASL)
Clin Mol Hepatol 2019;25(2):93-159.
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Original Article

Viral hepatitis

Characterization and evaluation of liver fibrosis grade in patients with chronic hepatitis B virus infection and normal transaminases
San Juan López Cristina, Casado Martín Marta, González Sánchez Mercedes, Porcel Martín Almudena, Hernández Martínez Álvaro, Vega Sáenz Jose Luis, Parrón Carreño Tesifón
Clin Mol Hepatol 2018;24(4):384-391.
Published online July 4, 2018
DOI: https://doi.org/10.3350/cmh.2018.0004
Backgrounds/Aims
The
objective
of our study was to determine the epidemiological, laboratory, and serological characteristics of patients with chronic hepatitis B virus (HBV) infection and normal transaminases. The study also aimed to evaluate liver damage by measuring the liver fibrosis (LF) grade and to identify possible factors associated with the presence of fibrosis.
Methods
A retrospective observational study was conducted in patients with chronic HBV infection and classified as inactive carriers or immune-tolerant. Epidemiological variables of age, sex, immigrant, alcohol consumption, and body mass index (BMI), as well as virological variables (HBV DNA) and transaminase level were collected throughout the follow-up. The LF grade was evaluated by transient elastography. The cutoff value for significant fibrosis (SF) was liver stiffness ≥7.9 kPa.
Results
A total of 214 patients were included in the analysis, and 62% of them had a BMI ≥25 kg/m2 . During follow-up, 4% of patients showed transaminase elevation (<1.5 times normal). Most patients had a viral DNA level <2,000 IU/mL (83%). Data on LF were available in 160 patients; of these, 14% had SF, 9% F3, and 6% F4. The variables associated with the presence of SF were transaminase alteration during follow-up, as 23% of patients with SF had elevated transaminases versus 3% of patients without SF (P<0.005), and BMI, as the vast majority of patients with SF (88%) had a BMI ≥25 kg/m2 versus 56% of patients without SF (P<0.05).
Conclusions
In patients with chronic HBV infection and normal transaminases, liver damage does not seem to be related to DNA levels, alcohol consumption, or immigrant status. SF seems to be associated with transaminase alteration during follow-up and elevated BMI. It is therefore recommended to measure LF grade with validated non-invasive methods in such patients.

Citations

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Review

Viral hepatitis

Management of chronic hepatitis B patients in immunetolerant phase: what latest guidelines recommend
Grace Lai-Hung Wong
Clin Mol Hepatol 2018;24(2):108-113.
Published online January 22, 2018
DOI: https://doi.org/10.3350/cmh.2017.0068
The natural history of chronic hepatitis B (CHB) is complex and may run through different immune phases that may overlap. In particulars, the immune-tolerant phase is the most interesting and not as well understood as we thought. The concept of true immune tolerance have been under challenged from immunology points of view. The major international guidelines have not yet reached a consensus on the definition of the immune-tolerant phase. While positive hepatitis B e antigen (HBeAg), high serum hepatitis B virus (HBV) DNA and normal serum alanine aminotransferase (ALT) levels are the three key features of this phase, some guidelines also put age into consideration. A new nomenclature, Phase 1 or HBeAg-positive chronic HBV infection, is given by the latest European Association for the Study of the Liver (EASL) published in April 2017. While current guidelines advise against starting antiviral treatment for immune-tolerant CHB patients, some new data suggest treating such patients may reduce the risk of liver fibrosis progression and hepatocellular carcinoma.

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Editorial

Viral hepatitis

Is it possible to predict the development of an entecavir resistance mutation in patients with chronic hepatitis B in clinical practice?
Joon Yeul Nam, Jeong-Hoon Lee
Clin Mol Hepatol 2017;23(4):311-313.
Published online December 4, 2017
DOI: https://doi.org/10.3350/cmh.2017.0069

Citations

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  • Hepatitis B virus resistance to nucleos(t)ide analogue therapy: WHO consultation on questions, challenges, and a roadmap for the field
    Sheila F Lumley, Jolynne Mokaya, Tongai G Maponga, Anna Kramvis, Geoffrey Dusheiko, William Irving, Marion Delphin, Khadija Said Mohammed, Louise O Downs, Elizabeth Waddilove, Motswedi Anderson, Collins Iwuji, Nokukhanya Msomi, Ponsiano Ocama, Saeed Hamid
    The Lancet Microbe.2025; 6(8): 101076.     CrossRef
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  • 148 Download
  • 1 Web of Science
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Case Report

Viral hepatitis

Favorable effect of corticosteroids in treating acute-on-chronic liver failure underlying chronic hepatitis B
Hyeji Kim, Jung Hyun Kwon, Yong Hee Kim, Soon Woo Nam, Jong Yul Lee, Jeong Won Jang
Clin Mol Hepatol 2018;24(4):430-435.
Published online November 27, 2017
DOI: https://doi.org/10.3350/cmh.2017.0016
Acute-on-chronic liver failure (ACLF) occurs in the presence of a chronic liver disease or cirrhosis, and often results from exacerbation of chronic hepatitis B (CHB). The efficacy of corticosteroid treatment in ACLF patients with underlying CHB remains unclear. We report the case of a 50-year-old woman who experienced ACLF due to CHB exacerbation and was treated with a combination of corticosteroids and nucleot(s)ide analogue (NUC). The patient showed rapid decompensation due to CHB exacerbation. Three months of antiviral therapy produced no improvement in liver function. Combination therapy with corticosteroids and NUC was started, which did result in improvement of liver function. This case shows that the combined therapy of corticosteroids and NUC can be effective in treating ACLF due to CHB exacerbation.

Citations

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  • Metabolic dysfunction-associated steatotic liver disease (MASLD): Exploring systemic impacts and innovative therapies
    Parag Jain, Akanksha Jain, Rohitas Deshmukh, Pradeep Samal, Trilochan Satapathy, Ajazuddin
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  • Hypomethylation of thymosin β4 promoter is associated with glucocorticoid therapy in patients with acute-on-chronic hepatitis B-induced liver failure
    He Wang, Yu Qian, Jing-Wen Wang, Yu Fang, Yu-Chen Fan, Hui-Hui Liu, Kai Wang
    International Health.2023; 15(1): 19.     CrossRef
  • Critically Ill COVID-19 Patient with Chronic Liver Disease - Insights into a Comprehensive Liver Intensive Care
    Cyriac Abby Philips, Kamna Kakkar, Moby Joseph, Praveen Kumar Yerol, Rizwan Ahamed, Sasidharan Rajesh, Philip Augustine
    Journal of Clinical and Translational Hepatology.2021; 000(000): 000.     CrossRef
  • 14,060 View
  • 262 Download
  • 3 Web of Science
  • Crossref

Editorial

Viral hepatitis

Is tenofovir monotherapy a sufficient defense line against multi-drug resistant hepatitis B virus?
Yun Bin Lee, Jeong-Hoon Lee
Clin Mol Hepatol 2017;23(3):219-221.
Published online September 19, 2017
DOI: https://doi.org/10.3350/cmh.2017.0045

Citations

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  • Hepatitis B virus resistance to tenofovir: fact or fiction? A systematic literature review and structural analysis of drug resistance mechanisms
    Jolynne Mokaya, Anna L. McNaughton, Phillip A Bester, Dominique Goedhals, Eleanor Barnes, Brian D Marsden, Philippa C. Matthews
    Wellcome Open Research.2020; 5: 151.     CrossRef
  • Entecavir+tenofovir vs. lamivudine/telbivudine+adefovir in chronic hepatitis B patients with prior suboptimal response
    Hyun Young Woo, Jun Yong Park, Si Hyun Bae, Chang Wook Kim, Jae Young Jang, Won Young Tak, Dong Joon Kim, In Hee Kim, Jeong Heo, Sang Hoon Ahn
    Clinical and Molecular Hepatology.2020; 26(3): 352.     CrossRef
  • 10,536 View
  • 155 Download
  • 1 Web of Science
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Original Articles

Viral hepatitis

Efficacy of tenofovir-based rescue therapy for chronic hepatitis B patients with resistance to lamivudine and entecavir
Hee-Jeong Jeon, Seok Won Jung, Neung Hwa Park, Yujin Yang, Jin-Hee Noh, Jae-Sung Ahn, Hyung Rae Kim, Jae Ho Lee, Jung Woo Shin
Clin Mol Hepatol 2017;23(3):230-238.
Published online June 30, 2017
DOI: https://doi.org/10.3350/cmh.2017.0003
Background/Aims
Tenofovir disoproxil fumarate (TDF) monotherapy for 48 weeks provided a virological response comparable to that of TDF and entecavir (ETV) combination therapy in patients infected with ETV-resistant hepatitis B virus (HBV). Little long-term data in routine clinical practice are available regarding the optimal treatment of patients with ETV-resistant HBV.
Methods
We investigated the long-term antiviral efficacy of combination therapy of TDF+lamivudine (LAM) or TDF+ETV compared to that of TDF monotherapy in 73 patients with resistance to both LAM and ETV.
Results
Patients were treated with TDF monotherapy (n=12), TDF+LAM (n=19), or TDF+ETV (n=42) for more than 6 months. The median duration of TDF-based rescue therapy was 37 months. Virologic response (VR) was found in 63 patients (86.3%). The rates of VR among the three groups (TDF monotherapy, TDF+LAM, and TDF+ETV) were not statistically different (log-rank P=0.200) at 12 months (59.3%, 78.9%, and 51.8%, respectively) or at 24 months (88.4%, 94.7%, and 84.2%). In addition, treatment efficacy of TDF-based combination or TDF monotherapy was not statistically different with ETV-resistant strains or exposure to other antiviral agents. In multivariate analysis, only lower baseline HBV DNA level was an independent predictor for VR (hazard ratio, 0.723; 95% confidence interval, 0.627-0.834; P<0.001).
Conclusions
TDF monotherapy was as effective as combination therapy of TDF+LAM or TDF+ETV in maintaining long-term viral suppression in chronic hepatitis B patients with resistance to both LAM and ETV. HBV DNA level at the start of TDF rescue therapy was the only independent predictor of subsequent VR.

Citations

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  • Efficacy and Safety of Tenofovir Plus Entecavir Combination Therapy Versus Tenofovir Monotherapy in Chronic Hepatitis B Virus Patients With Resistance or Partial Response to Entecavir: A Systematic Review and Meta-analysis
    Syed H. Ali, Muhammad H. Shah, Sakshi Roy, Hareesha R. Bharadwaj, Joecelyn K. Tan, Medha S. Rao, Muhtasim Fuad, Arjun Ahluwalia, Aditya Gaur, Priyal Dalal, Arkadeep Dhali, Harishankar Gopakumar
    Journal of Clinical and Experimental Hepatology.2025; 15(4): 102541.     CrossRef
  • Tenofovir-Associated Kidney Dysfunction and Bone Fracture: A Case Report and Literature Review
    KK Athish, Shobhana Nayak Rao, Venkat H Marimuthu, Vamsi Krishna, Anwadevi Arun
    Cureus.2024;[Epub]     CrossRef
  • Bilateral atraumatic neck of femur fractures secondary to tenofovir-induced fanconi syndrome
    Vikaesh Moorthy, Kelvin Guoping Tan
    Journal of Orthopaedic Reports.2023; 2(1): 100123.     CrossRef
  • Molecular characterization of hepatitis B virus (HBV) isolated from a pediatric case of acute lymphoid leukemia, with a delayed response to antiviral treatment: a case report
    Chien-Yu Chen, Christina Hajinicolaou, Priya Walabh, Luicer Anne Olubayo Ingasia, Ernest Song, Anna Kramvis
    BMC Pediatrics.2022;[Epub]     CrossRef
  • Tenofovir Alafenamide Fumarate, Tenofovir Disoproxil Fumarate and Entecavir: Which is the Most Effective Drug for Chronic Hepatitis B? A Systematic Review and Meta-analysis
    Xuefeng Ma, Shousheng Liu, Mengke Wang, Yifen Wang, Shuixian Du, Yongning Xin, Shiying Xuan
    Journal of Clinical and Translational Hepatology.2021; 000(000): 000.     CrossRef
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    F. Higuera-de-la-Tijera, G.E. Castro-Narro, J.A. Velarde-Ruiz Velasco, E. Cerda-Reyes, R. Moreno-Alcántar, I. Aiza-Haddad, M. Castillo-Barradas, L.E. Cisneros-Garza, M. Dehesa-Violante, J. Flores-Calderón, M.S. González-Huezo, E. Márquez-Guillén, L.E. Muñ
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  • Asociación Mexicana de Hepatología A.C. Guía Clínica de Hepatitis B
    F. Higuera-de-la-Tijera, G.E. Castro-Narro, J.A. Velarde-Ruiz Velasco, E. Cerda-Reyes, R. Moreno-Alcántar, I. Aiza-Haddad, M. Castillo-Barradas, L.E. Cisneros-Garza, M. Dehesa-Violante, J. Flores-Calderón, M.S. González-Huezo, E. Márquez-Guillén, L.E. Muñ
    Revista de Gastroenterología de México.2021; 86(4): 403.     CrossRef
  • Entecavir+tenofovir vs. lamivudine/telbivudine+adefovir in chronic hepatitis B patients with prior suboptimal response
    Hyun Young Woo, Jun Yong Park, Si Hyun Bae, Chang Wook Kim, Jae Young Jang, Won Young Tak, Dong Joon Kim, In Hee Kim, Jeong Heo, Sang Hoon Ahn
    Clinical and Molecular Hepatology.2020; 26(3): 352.     CrossRef
  • Tenofovir‐based combination therapy or monotherapy for multidrug‐resistant chronic hepatitis B: Long‐term data from a multicenter cohort study
    Hyung Joon Yim, Sang Jun Suh, Young Kul Jung, Seong Gyu Hwang, Yeon Seok Seo, Soon Ho Um, Sae Hwan Lee, Young Seok Kim, Jae Young Jang, In Hee Kim, Hyoung Su Kim, Ji Hoon Kim, Young Sun Lee, Eileen L. Yoon, Myeong Jun Song, Jun Yong Park
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    Si-Si Yang, Cheng-Wei Cai, Xue-Qing Ma, Jia Xu, Cheng-Bo Yu
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    Hye Won Lee, Jun Yong Park, Jin Woo Lee, Ki Tae Yoon, Chang Wook Kim, Hana Park, Young Seok Kim, Soon Ku Paik, Jung Il Lee, Beom Kyung Kim, Kwang-Hyub Han, Sang Hoon Ahn
    Clinical Gastroenterology and Hepatology.2019; 17(7): 1348.     CrossRef
  • Risk factors associated with hypophosphatemia in chronic Hepatitis B patients treated with tenofovir disoproxil fumarate
    Dohyeong Lee, Byung Cheol Yun, Kwang Il Seo, Byung Hoon Han, Sang Uk Lee, Eun Taek Park, Jin Wook Lee, Joonho Jeong
    Medicine.2019; 98(50): e18351.     CrossRef
  • Effect of tenofovir on renal function in patients with chronic hepatitis B
    Woo Jin Jung, Jae Young Jang, Won Young Park, Soung Won Jeong, Hee Jeong Lee, Sang Joon Park, Sae Hwan Lee, Sang Gyune Kim, Sang-Woo Cha, Young Seok Kim, Young Deok Cho, Hong Soo Kim, Boo Sung Kim, Suyeon Park, Baigal Baymbajav
    Medicine.2018; 97(7): e9756.     CrossRef
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    Mauro Viganò, Alessandro Loglio, Pietro Lampertico
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    Yun Bin Lee, Jeong-Hoon Lee
    Clinical and Molecular Hepatology.2017; 23(3): 219.     CrossRef
  • 13,259 View
  • 171 Download
  • 13 Web of Science
  • Crossref

Hepatic neoplasm

Risk score model for the development of hepatocellular carcinoma in treatment-naïve patients receiving oral antiviral treatment for chronic hepatitis B
Won Sohn, Ju-Yeon Cho, Ji Hoon Kim, Jung Il Lee, Hyung Joon Kim, Min-Ah Woo, Sin-Ho Jung, Yong-Han Paik
Clin Mol Hepatol 2017;23(2):170-178.
Published online May 16, 2017
DOI: https://doi.org/10.3350/cmh.2016.0086
Background/Aims
This study aimed to develop and validate a risk prediction model for the development of hepatocellular carcinoma (HCC) in treatment-naïve patients receiving oral antiviral treatment for chronic hepatitis B (CHB).
Methods
We investigated 2,061 Korean treatment-naïve patients with CHB treated with entecavir as an initial therapy. A risk score model for HCC development was developed based on multivariable Cox regression model in a single center (n=990) and was validated using the time-dependent area under the receiver operating characteristic curve (AUROC) in three other centers (n=1,071). The difference of HCC development among risk groups (low, intermediate, and high) categorized by risk score was also investigated.
Results
The cumulative incidence rates of HCC at 5 years were 11.2% and 8.9% in the testing and validation cohorts, respectively. HCC-Risk Estimating Score in CHB patients Under Entecavir (HCC-RESCUE) is formulated as (age+15×gender [female=0 / male=1]+23×cirrhosis [absence=0 / presence=1]). The AUROCs at 1 year, 3 years, and 5 years were 0.82, 0.81, and 0.81, respectively, in the validation cohort. A significant difference of HCC development in each risk group was determined by the 5-year HCC risk score in the validation cohort (low risk group, 2.1%; intermediate risk group, 9.3%; high risk group, 41.2%, p<0.001).
Conclusions
The study presents a new risk score model with a good ability to predict HCC development and determine high risk patients for HCC development consisting of readily available clinical factors in treatment-naïve CHB patients receiving entecavir.

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