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Correspondence

Correspondence to editorial on “Factors associated with hepatitis B mother-to-child transmission in a national prevention program”: Redefining MTCT prevention strategies toward HBV elimination
Moran Ki, Jong-Hyun Kim
Received July 21, 2025  Accepted July 24, 2025  Published online July 28, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0805    [Accepted]
  • 1,323 View
  • 30 Download

Research Letter

Contemporary Trends in Extrahepatic Mortality of Chronic Liver Disease in the United States from 2014 to 2023
Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, Aijaz Ahmed
Received July 23, 2025  Accepted July 23, 2025  Published online July 28, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0802    [Accepted]
  • 1,972 View
  • 41 Download

Review

Global strategies and actions to eliminate hepatitis B virus infection
Chih-Lin Lin, Jia-Horng Kao
Clin Mol Hepatol 2025;31(4):1197-1212.
Published online July 28, 2025
DOI: https://doi.org/10.3350/cmh.2025.0492
Through the implementation of hepatitis B vaccination and effective antiviral treatment over the past four decades, the hepatitis B surface antigen (HBsAg) seroprevalence of the vaccinated generation dramatically decline. The incidence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) also decreases. However, the elimination of HBV is still a challenge to achieve. Novel HBV biomarkers, including quantitative HBsAg, hepatitis B virus core-related antigen and HBV RNA are promising in predicting clinical phases, risks of disease progression and HBV functional cure. Current antiviral therapies, nucleoside/nucleotide and pegylated alpha-interferon, effectively decrease HCC incidence in chronic hepatitis B (CHB) patients and minimize the recurrence of HCC in patients receiving curative therapy. Novel agents under development to achieve HBV cure include direct-acting antivirals that target various stages of the HBV lifecycle and host targeting agents that enhance HBV-specific immunity. The action plans for eliminating hepatitis B in the future are universal HBV screening, early and simplified treatment as well as precision lifelong management for CHB patients. This narrative review will summarize and discuss global strategies and initiatives aimed at eliminating HBV infection.

Citations

Citations to this article as recorded by  Crossref logo
  • 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
  • 3,481 View
  • 183 Download
  • Crossref

Editorial

Redefining MTCT prevention strategies toward HBV elimination: Editorial on “Factors associated with hepatitis B mother-to-child transmission in a national prevention program”
Eunho Choi, Ji Hoon Kim, Young-Sun Lee
Received July 8, 2025  Accepted July 11, 2025  Published online July 14, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0747    [Epub ahead of print]
  • 2,016 View
  • 22 Download

Original Article

Factors associated with hepatitis B mother-to-child transmission in a national prevention program
Moran Ki, Byung-Woo Kim, Dahye Baik, Jong-Hyun Kim
Clin Mol Hepatol 2025;31(4):1298-1315.
Published online June 24, 2025
DOI: https://doi.org/10.3350/cmh.2025.0214
Background/Aims
Hepatitis B virus (HBV) mother-to-child transmission (MTCT) remains a global health concern, with over 90% of perinatal infections leading to chronic HBV. To evaluate long-term trends in MTCT rates and associated factors within Korea’s national program.
Methods
Population-based cohort study using linked data from the Perinatal Hepatitis B Prevention Program (PHBPP) and National Health Insurance Service in Korea. The study included HBsAg-positive mother-infant pairs with post-vaccination serologic results from 2002 to 2021.
Results
Among the 154,478 mother-infant pairs, the overall MTCT rate after prophylaxis was 2.3%. Antiviral use lowered MTCT rates (0.9% vs. 2.4%) particularly in HBeAg-positivity (1.0% vs. 5.9%; adjusted odds ratio [aOR] 0.21; 95% confidence interval [CI] 0.14–0.32). Lower MTCT rates were observed for cesarean section vs. vaginal delivery (1.9% vs. 2.6%; aOR 0.78; 95% CI 0.73–0.84) and breastfeeding vs. formula feeding (1.8% vs. 2.8%; aOR 0.65; 95% CI 0.56–0.76). Annual MTCT rates decreased from 3.6% (2002–2005) to 1.3% (2018–2021). Antivirals reduced MTCT rates; initiation at 14–27 weeks (0.39%), or 28–32 weeks (0.44%) vs. ≥33 weeks (1.47%); postpartum continuation (0.55%) vs. antepartum discontinuation (1.44%); use ≥61 days (0.51%) vs. 1–60 days (1.67%). Lower MTCT risk was associated with maternal (old age, high income) and infant (female sex, preterm birth) factors.
Conclusions
This comprehensive analysis of the PHBPP in Korea demonstrates that the use of antivirals, breastfeeding, and cesarean section, combined with conventional immunoprophylaxis, has significantly reduced MTCT rates. These results are crucial for global HBV elimination and can help to guide HBV MTCT prevention strategies.
  • 2,713 View
  • 137 Download
  • 1 Web of Science

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
Received May 4, 2025  Accepted May 8, 2025  Published online May 13, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0500    [Epub ahead of print]
  • 2,771 View
  • 19 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
  • 6,210 View
  • 64 Download

Correspondence

Correspondence to editorial on “Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial”
Hyung Joon Yim, Seong Hee Kang, Young Kul Jung, Jin Mo Yang
Received April 7, 2025  Accepted April 8, 2025  Published online April 15, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0379    [Epub ahead of print]
  • 2,970 View
  • 24 Download

Editorials

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
Received April 3, 2025  Accepted April 8, 2025  Published online April 11, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0369    [Epub ahead of print]
  • 3,187 View
  • 34 Download
Viral manipulation of host cell glutamine metabolism and glutamine rewiring in hepatic diseases: Editorial on “Glutamate dehydrogenase 1-dependent α-ketoglutarate promotes hepatitis B virus transcription by modulating histone methylations on the covalently closed circular DNA minichromosome”
Mehrangiz Dezhbord, Kyun-Hwan Kim
Received April 2, 2025  Accepted April 8, 2025  Published online April 11, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0366    [Epub ahead of print]
  • 2,728 View
  • 70 Download

Original Article

Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues
Rui Huang, Dae Won Jun, Hidenori Toyoda, Yao-Chun Hsu, Huy Trinh, Akito Nozaki, Toru Ishikawa, Tsunamasa Watanabe, Haruki Uojima, Daniel Q. Huang, Takashi Honda, Yasuhito Tanaka, Philip Vutien, Sebastián Marciano, Hiroshi Abe, Masaru Enomoto, Masanori Atsukawa, Hirokazu Takahashi, Kunihiko Tsuji, Koichi Takaguchi, Pei-Chien Tsai, Chia-Yen Dai, Jee-Fu Huang, Chung-Feng Huang, Ming-Lun Yeh, Eileen Yoon, Sung Eun Kim, Sang Bong Ahn, Gi-Ae Kim, Jang Han Jung, Soung Won Jeong, Hyunwoo Oh, Cheng-Hao Tseng, Masatoshi Ishigami, Angela Chau, Mayumi Maeda, Satoshi Yasuda, Makoto Chuma, Takanori Ito, Keigo Kawashima, Joanne Kimiko Liu, Adrian Gadano, Ritsuzo Kozuka, Norio Itokawa, Kaori Inoue, Tomonori Senoh, Jie Li, Wan-Long Chuang, Ramsey Cheung, Chao Wu, Ming-Lung Yu, Mindie H. Nguyen
Clin Mol Hepatol 2025;31(3):1003-1017.
Published online March 17, 2025
DOI: https://doi.org/10.3350/cmh.2024.1070
Background/Aims
Given the increase in prevalence of metabolic diseases, we investigated their long-term impacts on the outcomes of chronic hepatitis B (CHB) patients receiving nucleos(t)ide analogue (NA) treatment.
Methods
We analyzed data from CHB patients for whom initiated NA treatment from 30 centers. We balanced patient characteristics with and without metabolic disease (diabetes, obesity, dyslipidemia, and hypertension) via propensity-score matching (PSM) to evaluate adverse outcomes.
Results
The study included 4,500 patients. PSM yielded 909 pairs of patients with balanced characteristics. When stratified by the number of metabolic diseases, only patients with ≥2 metabolic diseases had an increased cumulative incidence of cirrhosis and overall death. However, when stratified by the presence of diabetes (regardless of the presence or number of other metabolic diseases), patients with diabetes (versus those without) had a significantly higher cumulative incidence of all outcomes: cirrhosis (P=0.009), hepatocellular carcinoma (HCC, P=0.023), and overall, liver-related, and non-liver-related death (P<0.001, P=0.026 and P<0.001, respectively). Having ≥2 metabolic diseases was associated with cirrhosis, overall death, and non-liver-related death but not HCC or liver-related death, while diabetes was significantly associated with a higher risk of all outcomes: cirrhosis (hazard ratio [HR]=3.75, P=0.004), HCC (HR=2.02, P=0.020), and overall, liver-related, and non-liver-related death (HR=2.53, P<0.001; HR=2.65, P=0.016; HR=2.38, P<0.001).
Conclusions
Having two or more metabolic diseases was associated with a higher risk of cirrhosis, overall death, and non-liver-related death, but having diabetes as a single metabolic disease was significantly associated with all adverse outcomes including cirrhosis, HCC, and overall, liver-related, and non-liver-related death.

Citations

Citations to this article as recorded by  Crossref logo
  • 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
  • 9,814 View
  • 205 Download
  • 6 Web of Science
  • Crossref

Editorials

Regulation of hepatitis B virus cccDNA by metabolic pathways: Editorial on “GDH1-dependent α-ketoglutarate promotes HBV transcription by modulating histone methylations on the cccDNA minichromosome”
Hyeong-Jin Cho, Sung-Gyoo Park
Received March 4, 2025  Accepted March 9, 2025  Published online March 12, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0255    [Epub ahead of print]

Citations

Citations to this article as recorded by  Crossref logo
  • Establishment and evaluation of an immortalized dzo kidney cell line
    Wenkai Liu, Cong Xu, Jiamin Wang, Na Sun, Zhongren Ma, Jin Zhao, Jianguo Chen, You Li, Zilin Qiao
    Scientific Reports.2025;[Epub]     CrossRef
  • 3,515 View
  • 79 Download
  • Crossref
Can SAFE score be utilized as a universal hepatocellular carcinoma prediction score?: Editorial on “High Steatosis-Associated Fibrosis Estimator scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic dysfunction-associated steatotic liver disease”
Michael Kwan-Lung Ko, Loey Lung-Yi Mak
Received February 3, 2025  Accepted February 7, 2025  Published online February 11, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0118    [Epub ahead of print]
  • 3,135 View
  • 33 Download

Original Article

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.2025;[Epub]     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.2025;[Epub]     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.2025;[Epub]     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
  • 7,929 View
  • 198 Download
  • 1 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
  • 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
  • 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.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
  • 11,746 View
  • 551 Download
  • 4 Web of Science
  • Crossref

Original Articles

Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial
Hyung Joon Yim, Yeon Seok Seo, Ji Hoon Kim, Won Kim, Young Kul Jung, Jae Young Jang, Sae Hwan Lee, Yun Soo Kim, Chang Wook Kim, Hyoung Su Kim, Jae-Jun Shim, Eun-Young Cho, In Hee Kim, Byung Seok Lee, Jeong-Hoon Lee, Byung Seok Kim, Jeong Won Jang, Hyun Woong Lee, Jung Hyun Kwon, Moon Young Kim, Do Seon Song, Jung Gil Park, Yoon Seok Lee, Eileen L. Yoon, Han Ah Lee, Seong Hee Kang, Jin Mo Yang
Clin Mol Hepatol 2025;31(3):810-822.
Published online January 17, 2025
DOI: https://doi.org/10.3350/cmh.2024.0819
Background/Aims
Besifovir (BSV) showed comparable antiviral activity and superior safety profiles to tenofovir disoproxil fumarate (TDF) in treatment-naïve chronic hepatitis B (CHB). However, no data are available regarding the antiviral efficacy and safety of BSV in patients with CHB who switched from long-term TDF to BSV. This study aimed to evaluate the outcome of a 48-week BSV therapy in patients with CHB who switched from long-term TDF treatment.
Methods
In this non-inferiority trial, 153 CHB patients treated with TDF for ≥48 weeks who had hepatitis B virus (HBV) DNA <20 IU/mL were randomized to receive either BSV 150 mg or TDF 300 mg for 48 weeks.
Results
The per-protocol analysis included 130 patients (BSV group, 64; TDF group, 66). The median duration of TDF use before enrollment was 4.14 years. After 48 weeks, 100.0% and 98.5% patients in the BSV and TDF groups, respectively, met the primary endpoint (HBV DNA <20 IU/mL), demonstrating the non-inferior antiviral efficacy of BSV to TDF (95% confidence interval –0.01 to 0.04; P>0.999), with a predefined margin of –0.18. The mean percentage changes in estimated glomerular filtration rates were slightly better in the BSV group (1.67±11.73%) than in the TDF group (–1.24±11.02%). The BSV group showed a significant improvement in bone turnover biomarkers compared to the TDF group; accordingly, hip and spine bone mineral density increased in the BSV group.
Conclusions
In patients with CHB receiving long-term TDF, switching to BSV may improve renal and bone safety with non-inferior antiviral efficacy compared to that of maintaining TDF.

Citations

Citations to this article as recorded by  Crossref logo
  • Tenofovir amibufenamide in chronic hepatitis B: Lipid changes and 144-week safety with tenofovir disoproxil fumarate-to-tenofovir amibufenamide switch
    Zhi-Hao Zeng, Jin-Qing Liu, Min Zhang, Cai-Liang Qiu, Zhen-Yu Xu
    World Journal of Gastroenterology.2025;[Epub]     CrossRef
  • 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.2025;[Epub]     CrossRef
  • 8,684 View
  • 157 Download
  • Crossref
High Steatosis-Associated Fibrosis Estimator scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic dysfunction-associated steatotic liver disease
Tung-Hung Su, Sheng-Shun Yang, Mei-Hsuan Lee, Wei-Yu Kao, Shang-Chin Huang, Fen-Fang Chen, Francis SK Poon, Lung-Wen Tsai, Yi-Ting Chen, Che Lin, Weichung Wang, W Ray Kim, Jia-Horng Kao
Clin Mol Hepatol 2025;31(3):796-809.
Published online January 6, 2025
DOI: https://doi.org/10.3350/cmh.2024.0822
Background/Aims
There are no hepatocellular carcinoma (HCC) surveillance recommendations for non-viral chronic liver diseases (CLD), such as metabolic dysfunction-associated steatotic liver disease (MASLD). We explored the Steatosis-Associated Fibrosis Estimator (SAFE) score to predict HCC in MASLD and other CLD etiologies.
Methods
Patients with various CLDs were included from medical centers in Taiwan. The SAFE score, consisting of age, body mass index, diabetes, and laboratory data, was calculated at baseline, and patients were traced for new development of HCC. The predictability of the SAFE score for HCC was analyzed using the sub-distribution hazard model with adjustments for competing risks.
Results
Among 12,963 CLD patients with a median follow-up of 4 years, 258 developed HCC. The SAFE score classifies 1-, 3-, and 5-year HCC risk regardless of CLD etiologies. High (≥100) and intermediate (0–100) SAFE scores increased 11 and 2 folds HCC risks compared to low (<0) SAFE scores. Combining two lower risk tiers (SAFE<100), a high SAFE score (≥100) was associated with a 7.5-fold risk of HCC (adjusted sub-distributional hazard ratio [aSHR] 7.54; 95% confidence interval (CI) 5.38–10.60). A high SAFE score increased the risks of HCC in subgroups of viral hepatitis, non-viral hepatitis (aSHR 11.10; 95% CI 3.97–31.30) and MASLD (aSHR 4.23; 95% CI 1.43–12.50). A hospital cohort (n=8,103) and a community MASLD cohort (n=120,166) validated the high SAFE score (≥100) for HCC risk prediction.
Conclusions
The SAFE score stratifies high risks for HCC in CLD patients regardless of etiologies and helps to select at-risk candidates for HCC surveillance.
  • 9,645 View
  • 356 Download

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
  • 4,574 View
  • 31 Download

Letter to the Editor

Viral hepatitis

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

Citations

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  • The burden of Parkinson’s disease, 1990–2021: a systematic analysis of the Global Burden of Disease study 2021
    Xi-Chen Wu, Yi-Yue Dong, Yu-Chen Ying, Guang-Yan Chen, Qian Fan, Ping Yin, Yue-Lai Chen
    Frontiers in Aging Neuroscience.2025;[Epub]     CrossRef
  • 5,558 View
  • 88 Download
  • 1 Web of Science
  • Crossref

Editorial

Viral hepatitis

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

Citations

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  • Expanding treatment eligibility for chronic hepatitis B: Balancing benefits, limitations, and healthcare access: Correspondence to editorial on “Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TOR
    Yao-Chun Hsu, Chi-Yi Chen, Jaw-Town Lin
    Clinical and Molecular Hepatology.2025; 31(2): e169.     CrossRef
  • 4,774 View
  • 39 Download
  • 1 Web of Science
  • Crossref

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

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  • Expanding treatment eligibility for chronic hepatitis B: Balancing benefits, limitations, and healthcare access: Correspondence to editorial on “Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TOR
    Yao-Chun Hsu, Chi-Yi Chen, Jaw-Town Lin
    Clinical and Molecular Hepatology.2025; 31(2): e169.     CrossRef
  • 4,763 View
  • 35 Download
  • 1 Web of Science
  • Crossref

Reviews

Viral hepatitis

Mechanisms of hepatocellular carcinoma and cirrhosis development in concurrent steatotic liver disease and chronic hepatitis B
Saisai Zhang, Lung-Yi Mak, Man-Fung Yuen, Wai-Kay Seto
Clin Mol Hepatol 2025;31(Suppl):S182-S195.
Published online November 21, 2024
DOI: https://doi.org/10.3350/cmh.2024.0837
Chronic hepatitis B (CHB) poses a major global public health challenge and is a leading cause of cirrhosis and liver cancer. Hepatic steatosis is common in individuals with CHB compared to the non-CHB population and is particularly prevalent in hepatitis B virus (HBV)-endemic regions, affecting about one-third of CHB patients. The interaction between hepatic steatosis and CHB-related disease progression is complex and still under debate. Evidence demonstrates that co-existing steatosis may worsen liver fibrosis while paradoxically increasing the likelihood of achieving better HBV control. In particular, despite the association of steatotic liver disease (SLD) with lower HBV viral loads and higher rates of HBsAg seroclearance, the coexistence of CHB and SLD can potentially accelerate liver disease progression. Factors such as fat deposition, lipotoxicity, oxidative stress, and chronic inflammation in SLD may foster a pro-fibrotic and pro-carcinogenic environment, accelerating the disease progression. Additionally, loss of global DNA methylation, changes in the immune microenvironment, and genetic susceptibility further contribute to the development of CHB-related cirrhosis and hepatocellular carcinoma (HCC). This review examines the mechanisms driving liver disease progression and the heightened risk of cirrhosis and HCC in patients with concurrent CHB and steatotic liver disease, underscoring the importance of prioritizing antiviral therapy for CHB in addition to addressing SLD.

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  • Evaluation of PNPLA3 genetic variants in Egyptian HBV-infected patients concomitant with metabolic-associated steatotic liver disease (MASLD)
    Mai Abd El-Meguid, Ghada M. Salum, Basma E. Fotouh, Naglaa Zayed, Shereen Abdel Alem, Ayman Yosry, Reham M. Dawood
    Diagnostic Microbiology and Infectious Disease.2026; 114(2): 117105.     CrossRef
  • Diagnostic Performance of Ultrasound-Derived Fat Fraction and Automated Point Shear Wave Elastography for Hepatic Steatosis and Fibrosis in Suspected Steatotic Liver Disease: A Prospective Multicenter Study
    Jing Liang, Xueqi Li, Guangwen Cheng, Huixiong Xu, Yuli Zhu, Zhe Ma, Dong Jiang, Hao Han, Lin Chen, Liyun Xue, Xiaohui Qiao, Hong Ding
    Ultrasound in Medicine & Biology.2026; 52(1): 227.     CrossRef
  • Pollutants in Microenvironmental Cellular Interactions During Liver Inflammation Cancer Transition and the Application of Multi-Omics Analysis
    Yulun Jian, Yuhan Li, Yanfeng Zhou, Wei Mu
    Toxics.2025; 13(3): 163.     CrossRef
  • Identification and evaluation of biomarkers for diagnosis of chronic hepatitis B using RNA-seq
    Hong Hong, Xintong Han, Qiuxiang Hu, Huafeng Song, Bing Han
    Virus Research.2025; 358: 199589.     CrossRef
  • Unraveling the metabolic thread: Type 2 diabetes and fibrosis in chronic hepatitis B with steatosis
    Won-Mook Choi, Wai-Kay Seto
    Hepatology.2025;[Epub]     CrossRef
  • Exosome in HBV infection: current concepts and future perspectives
    XueLan Yuan, ChunXia Huang, Yan Ran
    Frontiers in Cellular and Infection Microbiology.2025;[Epub]     CrossRef
  • Letter to the Editor on “Current Burden of Steatotic Liver Disease and Fibrosis among Adults in the United States, 2017-2023”
    Sisi Yang, Zhenxuan Ma
    Clinical and Molecular Hepatology.2025;[Epub]     CrossRef
  • Impact of Concurrent Steatotic Liver Disease and Chronic Hepatitis B on Treatment Response to Nucleos(t)ide Analogs
    Angela Chau, Jie Li, Dae Won Jun, Yao‐Chun Hsu, Hidenori Toyoda, Ming‐Lun Yeh, Tsunamasa Watanabe, Takashi Honda, Huy Trinh, Akito Nozaki, Haruki Uojima, Toru Ishikawa, Daniel Q. Huang, Philip Vutien, Sebastián Marciano, Hiroshi Abe, Masanori Atsukawa, Ma
    Journal of Viral Hepatitis.2025;[Epub]     CrossRef
  • Preoperative HBsAg seroclearance affects long-term outcomes for hepatitis B virus-related hepatocellular carcinoma after liver resection: a multicenter analysis
    Si-Yu Liu, Lin Zhu, Wen-Feng Lu, Gui-Lin Xie, Lei Liang, Jun-Wei Liu, Bin Ye, Mu-Gen Dai
    BMC Cancer.2025;[Epub]     CrossRef
  • Efficacy and safety of bifidobacterium triple viable capsules combined with entecavir in the treatment of Hepatitis B cirrhosis
    Rongquan Liu, Yun Ji, Jie Zhang
    Biomedical Papers.2025;[Epub]     CrossRef
  • EMP1 + hepatic stellate cells drive hepatic fibrosis progression to hepatocellular carcinoma and predict prognosis
    Jie You, Yihuan Huang, Chenhao Jiang, Jiaqi Xiao, Jiebin Zhang, Yasong Liu, Xin Sui, Yingcai Zhang, Jia Yao, Tongyu Lu
    Journal of Translational Medicine.2025;[Epub]     CrossRef
  • 7,256 View
  • 230 Download
  • 9 Web of Science
  • Crossref

Viral hepatitis

Prospect of emerging treatments for hepatitis B virus functional cure
Rex Wan-Hin Hui, Lung-Yi Mak, James Fung, Wai-Kay Seto, Man-Fung Yuen
Clin Mol Hepatol 2025;31(Suppl):S165-181.
Published online November 14, 2024
DOI: https://doi.org/10.3350/cmh.2024.0855
Functional cure, defined as sustained hepatitis B surface antigen (HBsAg) seroclearance with unquantifiable hepatitis B virus (HBV) DNA at 24 weeks off treatment, is a favorable treatment endpoint in chronic hepatitis B (CHB). Nonetheless, functional cure is rarely attained with the current treatment modalities of nucleos(t)ide analogues (NUCs) and pegylated interferon alpha. Multiple novel virus-targeting agents and immunomodulators are under development for HBV with functional cure as the treatment goal. Among virus-targeting agents, antisense oligonucleotides and small-interfering RNAs are the most advanced in the developmental pipeline, and can induce potent and sustainable HBsAg suppression. The other virus-targeting agents have varying effects on HBsAg and HBV DNA, depending on the drug mechanism. In contrast, immunomodulators have modest effects on HBsAg and have limited roles in monotherapy. Multiple combination regimens incorporating RNA interference agents with immunomodulators have been studied through many ongoing clinical trials. These combination strategies demonstrate synergistic effects in inducing functional cure, and will likely be the future direction of development. Despite the promising results, research is warranted to optimize treatment protocols and to establish criteria for NUC withdrawal after novel therapies. Functional cure is now an attainable target in CHB, and the emerging novel therapeutics will revolutionize CHB management.

Citations

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  • 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
  • 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
  • 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.2025;[Epub]     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
  • 8,286 View
  • 467 Download
  • 9 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
  • 4,072 View
  • 26 Download

Correspondence

Viral hepatitis

Correspondence to letter to the editor on “Contemporary awareness of viral hepatitis between 2012 and 2022 among Korean adults”
Chang Hun Lee, In Hee Kim, Sook-Hyang Jeong
Clin Mol Hepatol 2025;31(2):e149-e151.
Published online November 6, 2024
DOI: https://doi.org/10.3350/cmh.2024.0944
  • 4,716 View
  • 24 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

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  • Expanding treatment eligibility for chronic hepatitis B: Balancing benefits, limitations, and healthcare access: Correspondence to editorial on “Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TOR
    Yao-Chun Hsu, Chi-Yi Chen, Jaw-Town Lin
    Clinical and Molecular Hepatology.2025; 31(2): e169.     CrossRef
  • 4,393 View
  • 31 Download
  • 1 Web of Science
  • Crossref

Correspondence

Hepatic neoplasm

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

Citations

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  • Reply to correspondence on “Genetically-modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcinoma lesions in a clinical setting”
    Antonio Bertoletti, Anthony T Tan
    Clinical and Molecular Hepatology.2025; 31(1): e113.     CrossRef
  • 3,770 View
  • 56 Download
  • 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
  • 4,583 View
  • 40 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.
  • 5,793 View
  • 186 Download
  • 5 Web of Science

Reply to Correspondence

Hepatic neoplasm

Reply to correspondence on “Genetically-modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcinoma lesions in a clinical setting”
Antonio Bertoletti, Anthony T Tan
Clin Mol Hepatol 2025;31(1):e113-e116.
Published online October 11, 2024
DOI: https://doi.org/10.3350/cmh.2024.0867
  • 3,659 View
  • 37 Download

Letter to the Editor

Viral hepatitis

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

Citations

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  • Correspondence to letter to the editor on “Contemporary awareness of viral hepatitis between 2012 and 2022 among Korean adults”
    Chang Hun Lee, In Hee Kim, Sook-Hyang Jeong
    Clinical and Molecular Hepatology.2025; 31(2): e149.     CrossRef
  • 5,213 View
  • 53 Download
  • 1 Web of Science
  • Crossref

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
  • 4,140 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

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  • Reply to correspondence on “Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using vibration-controlled transient elastography: Systematic review and meta-analysis”
    Mirko Zoncapè, Emmanuel A. Tsochatzis
    Clinical and Molecular Hepatology.2025; 31(1): e117.     CrossRef
  • Correspondence to editorial on “Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using vibration-controlled transient elastography: Systematic review and meta-analysis”
    Young-Joo Jin, Seung Up Kim
    Clinical and Molecular Hepatology.2025; 31(1): e55.     CrossRef
  • Aspirin Use and Risk of HCC and Gastrointestinal Bleeding in Patients With HBV‐Related Cirrhosis: A Landmark Analysis
    Mi Na Kim, Geun U. Park, Seng Chan You, Jae Seung Lee, Hye Won Lee, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn
    Journal of Gastroenterology and Hepatology.2025; 40(11): 2750.     CrossRef
  • 5,759 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
  • 5,264 View
  • 62 Download
  • Crossref

Correspondences

Viral hepatitis

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
Clin Mol Hepatol 2025;31(1):e108-e109.
Published online August 5, 2024
DOI: https://doi.org/10.3350/cmh.2024.0619
  • 4,260 View
  • 40 Download

Viral hepatitis

Correspondence to editorial on “Core indicators related to the elimination of hepatitis B and C virus infection in South Korea: A nationwide study”
Chang Hun Lee, In Hee Kim, Sook-Hyang Jeong
Clin Mol Hepatol 2024;30(4):997-999.
Published online July 29, 2024
DOI: https://doi.org/10.3350/cmh.2024.0588
  • 4,251 View
  • 55 Download

Reply to Correspondence

Viral hepatitis

Reply to correspondence on “Hepatocellular carcinoma prediction model performance decreases with long-term antiviral therapy in chronic hepatitis B patients”
Beom Kyung Kim
Clin Mol Hepatol 2024;30(4):1044-1046.
Published online July 29, 2024
DOI: https://doi.org/10.3350/cmh.2024.0584

Citations

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  • Prediction Model for Familial Aggregated HBV‐Associated Hepatocellular Carcinoma Based on Serum Biomarkers
    Linmei Zhong, Guole Nie, Qiaoping Wu, Honglong Zhang, Haiping Wang, Jun Yan
    Cancer Reports.2025;[Epub]     CrossRef
  • 3,805 View
  • 31 Download
  • 1 Web of Science
  • 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

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    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
  • 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
  • 5,176 View
  • 128 Download
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Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using vibration-controlled transient elastography: Systematic review and meta-analysis
Young-Joo Jin, Hee Yeon Kim, Young Ju Suh, Chae Hyeon Lee, Jung Hwan Yu, Mi Na Kim, Ji Won Han, Han Ah Lee, Jihyun An, Young Eun Chon, Dae Won Jun, Miyoung Choi, Seung Up Kim
Clin Mol Hepatol 2024;30(Suppl):S159-S171.
Published online July 23, 2024
DOI: https://doi.org/10.3350/cmh.2024.0163
Backgrounds/Aims
Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) can assess fibrotic burden in chronic liver diseases. The systematic review and meta-analysis was conducted to determine whether LSM using VCTE can predict the risk of development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients.
Methods
A systematic literature search of the Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases (from January 2010 to June 2023) was conducted. Of the 1,345 individual studies identified, 10 studies that used VCTE were finally registered. Hazard ratios (HRs) and the 95% confidence intervals (CIs) were considered summary estimates of treatment effect sizes of ≥11 kilopascal (kPa) standard for HCC development. Meta-analysis was performed using the restricted Maximum Likelihood random effects model.
Results
Among the ten studies, data for risk ratios for HCC development could be obtained from nine studies. When analyzed for the nine studies, the HR for HCC development was high at 3.33 (95% CI, 2.45–4.54) in CHB patients with a baseline LSM of ≥11 kPa compared to patients who did not. In ten studies included, LSM of ≥11 kPa showed the sensitivity and specificity for predicting HCC development were 61% (95% CI, 50–71%) and 78% (95% CI, 66–86%), respectively, and the diagnostic accuracy was 0.74 (95% CI, 0.70–0.77).
Conclusions
The risk of HCC development was elevated in CHB patients with VCTE-determined LSM of ≥11 kPa. This finding suggests that VCTE-determined LSM values may aid the risk prediction of HCC development in CHB patients.

Citations

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  • 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
  • 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.2025;[Epub]     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
  • 5,531 View
  • 136 Download
  • 10 Web of Science
  • Crossref

Viral hepatitis

Non-linear association between liver fibrosis scores and viral load in patients with chronic hepatitis B
Gi-Ae Kim, Seung Won Choi, Seungbong Han, Young-Suk Lim
Clin Mol Hepatol 2024;30(4):793-806.
Published online July 19, 2024
DOI: https://doi.org/10.3350/cmh.2024.0252
Background/Aims
Serum hepatitis B virus (HBV) DNA levels and non-invasive liver fibrosis scores are significantly associated with hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients. Nonetheless, the relationship between HBV DNA levels and liver fibrosis scores is unclear.
Methods
A historical cohort comprising 6,949 non-cirrhotic Korean CHB patients without significant alanine aminotransferase elevation was investigated. The association of HBV DNA levels with the aspartate aminotransferase to platelet ratio index (APRI) and fibrosis (FIB)-4 score at baseline was analyzed using general linear models.
Results
In HBeAg-negative patients (n=4,868), HBV DNA levels correlated linearly with both APRI and FIB-4 scores. In contrast, in HBeAg-positive patients (n=2,081), HBV DNA levels correlated inversely with both APRI and FIB-4 scores. Across the entire cohort, a significant non-linear parabolic relationship was identified between HBV DNA levels and fibrosis scores, independent of age and other covariates. Notably, moderate viral loads (6–7 log10 IU/mL) corresponded to the highest APRI and FIB-4 scores (p<0.001). Over a median 10-year follow-up, 435 patients (6.3%) developed HCC. Higher APRI scores ≥0.5 and FIB-4 scores ≥1.45 were significantly associated with elevated HCC risk (p<0.001 for both). HBV DNA level remained a significant predictive factor for HCC development, even after adjusting for APRI or FIB-4 scores.
Conclusions
HBV viral load is significantly correlated with APRI and FIB-4 scores, and is also associated with HCC risk independent of those scores in CHB patients. These findings suggest that HBV DNA level is associated with hepatocarcinogenesis through both direct and indirect pathways.

Citations

Citations to this article as recorded by  Crossref logo
  • 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
    Clinical and Molecular Hepatology.2025; 31(1): e27.     CrossRef
  • 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
  • Early antiviral treatment with tenofovir alafenamide to prevent serious clinical adverse events in adults with chronic hepatitis B and moderate or high viraemia (ATTENTION): interim results from a randomised controlled trial
    Young-Suk Lim, Ming-Lung Yu, Jonggi Choi, Chi-Yi Chen, Won-Mook Choi, Wonseok Kang, Gi-Ae Kim, Hyung Joon Kim, Yun Bin Lee, Jeong-Hoon Lee, Neung Hwa Park, So Young Kwon, Soo Young Park, Ji Hoon Kim, Gwang Hyeon Choi, Eun Sun Jang, Chien-Hung Chen, Yao-Ch
    The Lancet Gastroenterology & Hepatology.2025; 10(4): 295.     CrossRef
  • Aspartate aminotransferase-to-platelet ratio index as a novel predictor of early mortality in heat stroke patients: a multi-centre retrospective study
    Min Wang, Yun Li, Yuan Cao, Meng-Meng Yang, Fu-Jing Liu, Jie Jiao, Sheng-Yuan Wang, Bin Song, Lu Wang, Yi-Qi Wu, Hong-Jun Kang
    Annals of Medicine.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
  • HBV activates hepatic stellate cells through RUNX2/ITGBL1 axis
    Fengchun Shi, Wei Tan, Wei Huang, Fei Ye, Mingjie Wang, Yongxiang Wang, Xinxin Zhang, Demin Yu
    Virology Journal.2025;[Epub]     CrossRef
  • EASL Clinical Practice Guidelines on the management of hepatitis B virus infection
    Markus Cornberg, Lisa Sandmann, Jerzy Jaroszewicz, Patrick Kennedy, Pietro Lampertico, Maud Lemoine, Sabela Lens, Barbara Testoni, Grace Lai-Hung Wong, Francesco Paolo Russo
    Journal of Hepatology.2025; 83(2): 502.     CrossRef
  • Geospatial patterns and socioeconomic determinants of the global acute viral hepatitis burden
    Ke-Jie He, Guoyu Gong
    Frontiers in Public Health.2025;[Epub]     CrossRef
  • Reevaluating antiviral thresholds in HBV DNA-negative inactive HBsAg carriers: a multicenter histopathological analysis
    Shan Ren, Sujun Zheng, Xinyang Zhang, Junliang Fu, Rongshan Fan, Qingfa Ruan, Wenqi Huang, Haibing Gao, Xiulan Xue, Fang Yang, Yao Xie, Minghui Li, Xinyue Chen
    Virology Journal.2025;[Epub]     CrossRef
  • Evaluating Non-Invasive Biomarkers and Composite Scores for Liver Fibrosis Diagnosis in Hepatitis B and C Infections
    Tamer A. Addissouky, Ibrahim El Tantawy El Sayed, Ayman E. El Agroudy, Yuliang Wang
    SN Comprehensive Clinical Medicine.2025;[Epub]     CrossRef
  • Viral Load–Based Prediction of Hepatocellular Carcinoma Risk in Noncirrhotic Patients With Chronic Hepatitis B
    Gi-Ae Kim, Young-Suk Lim
    Annals of Internal Medicine.2025; 178(9): 1365.     CrossRef
  • Revised REACH-B Model for Hepatocellular Carcinoma Risk Prediction in Patients With Chronic Hepatitis B
    Ju Dong Yang, Patrick S. Kamath
    Annals of Internal Medicine.2024; 177(10): 1435.     CrossRef
  • Decrease in HBsAg After TAF Switching from Entecavir During Long-Term Treatment of Chronic Hepatitis B Virus Infection
    Kazuto Tajiri, Yuka Hayashi, Aiko Murayama, Nozomu Muraishi, Masami Minemura, Ichiro Yasuda
    Viruses.2024; 17(1): 44.     CrossRef
  • 6,993 View
  • 246 Download
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Reply to Correspondence

Viral hepatitis

Reply to correspondence on “Novel role of MHC class II transactivator in hepatitis B virus replication and viral counteraction”
Cho-Rong Lee, Sung-Gyoo Park
Clin Mol Hepatol 2024;30(4):1053-1054.
Published online July 17, 2024
DOI: https://doi.org/10.3350/cmh.2024.0572

Citations

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  • Reply to correspondence on “Novel role of MHC class II transactivator in hepatitis B virus replication and viral counteraction”
    Cho-Rong Lee, Sung-Gyoo Park
    Clinical and Molecular Hepatology.2024; 30(4): 1053.     CrossRef
  • 4,264 View
  • 57 Download
  • 1 Web of Science
  • Crossref

Original Article

Liver fibrosis, cirrhosis, and portal hypertension

Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)
Chuan Liu, Hong You, Qing-Lei Zeng, Yu Jun Wong, Bingqiong Wang, Ivica Grgurevic, Chenghai Liu, Hyung Joon Yim, Wei Gou, Bingtian Dong, Shenghong Ju, Yanan Guo, Qian Yu, Masashi Hirooka, Hirayuki Enomoto, Amr Shaaban Hanafy, Zhujun Cao, Xiemin Dong, Jing LV, Tae Hyung Kim, Yohei Koizumi, Yoichi Hiasa, Takashi Nishimura, Hiroko Iijima, Chuanjun Xu, Erhei Dai, Xiaoling Lan, Changxiang Lai, Shirong Liu, Fang Wang, Ying Guo, Jiaojian Lv, Liting Zhang, Yuqing Wang, Qing Xie, Chuxiao Shao, Zhensheng Liu, Federico Ravaioli, Antonio Colecchia, Jie Li, Gao-Jun Teng, Xiaolong Qi
Clin Mol Hepatol 2025;31(1):105-118.
Published online July 11, 2024
DOI: https://doi.org/10.3350/cmh.2024.0198
Backgrounds/Aims
Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model.
Methods
Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort.
Results
In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM).
Conclusions
Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Citations

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  • Endoscopic variceal ligation combined with carvedilol versus endoscopic variceal ligation combined with propranolol for the treatment of oesophageal variceal bleeding in cirrhosis: study protocol for a multicentre, randomised controlled trial
    Yiling Li, Li Du, Shuairan Zhang, Chuan Liu, Chao Ma, Xiaochao Liu, Huanhai Xu, Zhixu Fan, Shengjuan Hu, Jing Wang, Lichun Shao, Lijun Peng, Huiling Xiang, Xuan Liang, Wenhui Zhang, Hongyun Zhao, Pengyuan He, Jingyi Xu, Qianlong Li, Ling Yang, Yunhai Wu,
    BMJ Open.2025; 15(4): e093866.     CrossRef
  • Relative change rate of liver stiffness measurements predicts the risk of liver decompensation in compensated advanced chronic liver disease
    Yanqiu Li, Zihang Qiao, Jinze Li, Bingbing Zhu, Yu Lu, Ying Feng, Xianbo Wang
    Clinical and Experimental Medicine.2025;[Epub]     CrossRef
  • Revolutionising portal hypertension diagnosis: the rise of non-invasive techniques in liver cirrhosis
    Bocheng Gao, Yumeng Lin, Huimin Zhang, Yulin Li, Shuhua Gou, Peiling Ma, Xueni Zhao, Yue Zhou, Qian Chen, Lan Yuan, Zhongyu Han, Chang Yu
    Frontiers in Medicine.2025;[Epub]     CrossRef
  • Editorial: Non‐selective beta‐blockers: A lifesaving shield for critically ill patients with acute decompensation of cirrhosis?
    Ling Yang, Chuan Liu, Jimmy Che‐To Lai, Xiaolong Qi
    Alimentary Pharmacology & Therapeutics.2024; 60(7): 965.     CrossRef
  • 7,789 View
  • 367 Download
  • 8 Web of Science
  • Crossref

Editorials

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
  • 3,497 View
  • 76 Download

Viral hepatitis

Class II transactivator restricts viral replication, extending its effect to HBV: Editorial on “Novel role of MHC class II transactivator in hepatitis B virus replication and viral counteraction”
Cho-Rong Lee, Sung-Gyoo Park
Clin Mol Hepatol 2024;30(4):724-727.
Published online July 3, 2024
DOI: https://doi.org/10.3350/cmh.2024.0465

Citations

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  • Next-generation T cell immunotherapy: overcoming exhaustion, senescence, and suppression
    Guangmei Li, Dengju Li, Xiaojian Zhu
    Frontiers in Immunology.2025;[Epub]     CrossRef
  • Correspondence on editorial regarding “Novel role of MHC class II transactivator in hepatitis B virus replication and viral counteraction”
    Mehrangiz Dezhbord, Kyun-Hwan Kim
    Clinical and Molecular Hepatology.2024; 30(4): 1028.     CrossRef
  • 4,170 View
  • 80 Download
  • 2 Web of Science
  • Crossref

Original Article

Hepatic neoplasm

Genetically-modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcinoma lesions in a clinical setting
Xueshuai Wan, Karin Wisskirchen, Tao Jin, Lu Yang, Xiaorui Wang, Xiang’an Wu, Fang Liu, Yu Wu, Christy Ma, Yong Pang, Qi Li, Ke Zhang, Ulrike Protzer, Shunda Du
Clin Mol Hepatol 2024;30(4):735-755.
Published online May 29, 2024
DOI: https://doi.org/10.3350/cmh.2024.0058
Background/Aims
Hepatitis B virus (HBV)-DNA integration in HBV-related hepatocellular carcinoma (HBV-HCC) can be targeted by HBV-specific T cells. SCG101 is an autologous, HBV-specific T-cell product expressing a T-cell receptor (TCR) after lentiviral transduction recognizing the envelope-derived peptide (S20-28) on HLA-A2. We here validated its safety and efficacy preclinically and applied it to an HBV-related HCC patient (NCT05339321).
Methods
Good Manufacturing Practice-grade manufactured cells were assessed for off-target reactivity and functionality against hepatoma cells. Subsequently, a patient with advanced HBV-HCC (Child-Pugh class A, Barcelona Clinic Liver Cancer stage B, Eastern Cooperative Oncology Group performance status 0, hepatitis B e antigen-, serum hepatitis B surface antigen [HBsAg]+, HBsAg+ hepatocytes 10%) received 7.9×107 cells/kg after lymphodepletion. Safety, T-cell persistence, and antiviral and antitumor efficacy were evaluated.
Results
SCG101, produced at high numbers in a closed-bag system, showed HBV-specific functionality against HBV-HCC cells in vitro and in vivo. Clinically, treatment was well tolerated, and all adverse events, including transient hepatic damage, were reversible. On day 3, ALT levels increased to 1,404 U/L, and concurrently, serum HBsAg started decreasing by 3.84 log10 and remained <1 IU/mL for over six months. HBsAg-expressing hepatocytes in liver biopsies were undetectable after 73 days. The patient achieved a partial response according to modified RECIST with a >70% reduction in target lesion size. Transferred T cells expanded, developed a stem cell-like memory phenotype, and were still detectable after six months in the patient’s blood.
Conclusions
SCG101 T-cell therapy showed encouraging efficacy and safety in preclinical models and in a patient with primary HBV-HCC and concomitant chronic hepatitis B with the capability to eliminate HBsAg+ cells and achieve sustained tumor control after single dosing.

Citations

Citations to this article as recorded by  Crossref logo
  • Clinical results of an HBV-specific T-cell receptor-T-cell therapy (SCG101) in patients with HBV-related hepatocellular carcinoma treated in an investigator-initiated, interventional trial
    Xiang'an Wu, Dongmei Quan, Wei Li, Karin Wisskirchen, Wei Wu, Yuhong Zhou, Yun-Peng Liu, Xueshuai Wan, Xiaorui Wang, Xuxu Zhang, Lu Yang, Mengyao Zheng, Ke Zhang, Ulrike Protzer, Shunda Du, Xiujuan Qu
    Gut.2026; 75(1): 147.     CrossRef
  • Reply to correspondence on “Genetically-modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcinoma lesions in a clinical setting”
    Antonio Bertoletti, Anthony T Tan
    Clinical and Molecular Hepatology.2025; 31(1): e113.     CrossRef
  • Correspondence to editorial on “Genetically-modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcinoma lesions in a clinical setting”
    Shunda Du, Karin Wisskirchen, Ke Zhang, Ulrike Protzer
    Clinical and Molecular Hepatology.2025; 31(1): e44.     CrossRef
  • T lymphocyte-based immune response and therapy in hepatocellular carcinoma: focus on TILs and CAR-T cells
    Thikra Majid Muhammed, Saade Abdalkareem Jasim, Ahmed Hussein Zwamel, Safia Obaidur Rab, Suhas Ballal, Abhayveer Singh, Anima Nanda, Subhashree Ray, Ahmed Hjazi, Hatif Abdulrazaq Yasin
    Naunyn-Schmiedeberg's Archives of Pharmacology.2025; 398(8): 10007.     CrossRef
  • Hepatitis B: Neue therapeutische Ansätze für eine funktionelle Heilung
    Markus Cornberg, Ulrike Protzer
    Deutsches Ärzteblatt Online.2025;[Epub]     CrossRef
  • Exploration of the role of immune cells and cell therapy in hepatocellular carcinoma
    Tao Zhang, Cong Ren, Zhanyu Yang, Ning Zhang, Haowen Tang
    Frontiers in Immunology.2025;[Epub]     CrossRef
  • Viral oncogenesis in cancer: from mechanisms to therapeutics
    Qing Xiao, Yi Liu, Tingting Li, Chaoyu Wang, Sanxiu He, Liuyue Zhai, Zailin Yang, Xiaomei Zhang, Yongzhong Wu, Yao Liu
    Signal Transduction and Targeted Therapy.2025;[Epub]     CrossRef
  • Unlocking T‐Cell Plasticity in the Tumor Microenvironment: Implications for Cancer Progression and Therapeutic Strategies
    Xiao‐Hong Ding, Xue‐Pei Li, Fenfang Chen, Han Wang, Yi‐Zhou Jiang
    MedComm – Oncology.2025;[Epub]     CrossRef
  • Immunotherapy for hepatocellular carcinoma
    Zhiqi Guan, Guiqi Zhu, Weiren Liu, Yinghong Shi
    Clinical Cancer Bulletin.2025;[Epub]     CrossRef
  • Chimeric antigen receptor (CAR) T-cell therapy: Engineering immune cells to treat liver diseases
    Elmar Jaeckel, Scott L. Friedman, Michael Hudecek, Ulrike Protzer
    Journal of Hepatology.2025; 83(5): 1156.     CrossRef
  • Adoptive T-cell therapy for virus-associated diseases
    Corey Smith, Rajiv Khanna, Graeme N. Forrest
    Clinical Microbiology Reviews.2025;[Epub]     CrossRef
  • CAR-T cell engineered with TCR-like antibody specific for HBV surface antigen epitope E183–91/HLA-A *0201 exhibit potent activity against HBV-HCC
    Fengling Wang, Jiaqian Li, Yong Huang, Feiyang Yan, Haozhan Gao, Weilin Zhou, Xinyu Gu, Dan Li, Yalan Zhang, Jing Li, Yuening Yang, Jiangping Yang, Mengxi Zhang, Jinrong Yang, Shimao Qi, Wei Wang
    OncoImmunology.2025;[Epub]     CrossRef
  • Targeting archetypes of viral-driven cancers with immunotherapy: a perspective on immunogenicity within the tumor microenvironment
    Keene Lee, Seohyun Kim, Junzhe Zhao, Shi Yong Neo
    Frontiers in Immunology.2025;[Epub]     CrossRef
  • T cells engineered to carry a high-affinity HBV-specific T cell receptor: a potent weapon against advanced HBV-related HCC
    Robert Thimme, Christoph Neumann-Haefelin
    Gut.2025; : gutjnl-2025-336452.     CrossRef
  • Do the therapeutic vaccines hold hope for the treatment of hepatitis B?
    Qiujing Yan, Xinghuan Fu, Yan Wang, Guiqiang Wang
    Hepatology International.2025;[Epub]     CrossRef
  • A highly selective TCR-mimic antibody reveals unexpected mechanisms of HBV peptide-MHC recognition and previously unknown target biology
    Shahzada Khan, Jeremy Lum, Heather Stephenson, Pawan Bir Kohli, David Mortenson, Dhivya Ramakrishnan, Magdeleine Hung, Sheng Ding, Elbert Seto, Sabrina Lu, Randy Yen, Debi Jin, Brian Lee, Sheila Clancy, Nicole Schirle Oakdale, Nikolai Novikov, Don Kang, R
    mAbs.2025;[Epub]     CrossRef
  • Combination therapies for chronic hepatitis B in the era of emerging novel drugs
    Dandan Weng, Chenxi Zhang, Qunyan Wei, Lukan Zhang, Xinya Zang, Guancheng Huang, Zhujun Cao, Qing Xie
    Hepatology International.2025;[Epub]     CrossRef
  • Adoptive cell therapy for HBV-associated liver diseases
    Youxi Zhou, Kaizhao Chen, Yang Zhang, Hongwei Cheng, Shuaishuai Zhang
    Biomedical Technology.2025; 12: 100116.     CrossRef
  • Recent Advances in Immune-based Therapy for Hepatocellular Carcinoma
    Kyung Won Park, Tae Hoon Park, Eun Ji Jang, Pil Soo Sung
    Journal of Digestive Cancer Research.2024; 12(2): 115.     CrossRef
  • Engineering HBV-specific T cells for the treatment of HBV-related HCC and HBV infection: Past, Present, and Future. Editorial on “Genetically-modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcin
    Antonio Bertoletti, Anthony T Tan
    Clinical and Molecular Hepatology.2024; 30(4): 728.     CrossRef
  • 8,078 View
  • 447 Download
  • 19 Web of Science
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Editorials

Steatotic liver disease

Metabolic dysfunction-associated fatty liver disease is a ubiquitous latent cofactor in viral- and alcoholic-related hepatocellular carcinoma: Editorial on “Global prevalence of metabolic dysfunction-associated fatty liver disease-related hepatocellular carcinoma: A systematic review and meta-analysis”
Toru Nakamura, Masahito Nakano, Tsubasa Tsutsumi, Keisuke Amano, Takumi Kawaguchi
Clin Mol Hepatol 2024;30(4):705-708.
Published online May 20, 2024
DOI: https://doi.org/10.3350/cmh.2024.0372

Citations

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  • Hepatocellular carcinoma surveillance after sustained virological response in chronic hepatitis C: Editorial on “Non-invasive prediction of post-sustained virological response hepatocellular carcinoma in hepatitis C virus: A systematic review and meta-ana
    Ho Soo Chun, Minjong Lee
    Clinical and Molecular Hepatology.2025; 31(1): 261.     CrossRef
  • Temporal Trends in Cardiovascular Mortality in Underlying Viral Hepatitis: A Retrospective Analysis of Gender, Racial/Ethnic, and Regional Disparities
    Wania Sultan, Haider Ashfaq, Hamza Ashraf, Ahmad Khan, Ayman Omair Hashmi, Muhammad Omar Larik, Maheen Zahid, Yasir Majeed, Pratik Bhattarai, Ashujot K. Dang, Ahmed Ali Aziz, Hafiz Muhammad Sharjeel Arshad
    JGH Open.2025;[Epub]     CrossRef
  • Metabolic dysfunction-associated fatty liver disease related hepatocellular carcinoma in China: An increasing problem: Letter to the edior on “Global prevalence of metabolic dysfunction-associated fatty liver disease-related hepatocellular carcinoma: A sy
    Xiangyu Wu, Wenjing Ni, Qianqian Chen, Junping Shi, Jie Li
    Clinical and Molecular Hepatology.2024; 30(4): 965.     CrossRef
  • Metabolic (dysfunction)-associated fatty liver disease metrics and contributions to liver research
    Maito Suoh, Saeed Esmaili, Mohammed Eslam, Jacob George
    Hepatology International.2024; 18(6): 1740.     CrossRef
  • 4,861 View
  • 77 Download
  • 4 Web of Science
  • Crossref

Viral hepatitis

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
Clin Mol Hepatol 2024;30(4):692-694.
Published online May 14, 2024
DOI: https://doi.org/10.3350/cmh.2024.0346

Citations

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  • 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
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Original Articles

Viral hepatitis

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
Clin Mol Hepatol 2024;30(3):539-560.
Published online May 14, 2024
DOI: https://doi.org/10.3350/cmh.2024.0060
Background/Aims
The major histocompatibility class II (MHC II) transactivator, known as CIITA, is induced by Interferon gamma (IFN-γ) and plays a well-established role in regulating the expression of class II MHC molecules in antigen-presenting cells.
Methods
Primary human hepatocytes (PHH) were isolated via therapeutic hepatectomy from two donors. The hepatocellular carcinoma (HCC) cell lines HepG2 and Huh7 were used for the mechanistic study, and HBV infection was performed in HepG2-NTCP cells. HBV DNA replication intermediates and secreted antigen levels were measured using Southern blotting and ELISA, respectively.
Results
We identified a non-canonical function of CIITA in the inhibition of hepatitis B virus (HBV) replication in both HCC cells and patient-derived PHH. Notably, in vivo experiments demonstrated that HBV DNA and secreted antigen levels were significantly decreased in mice injected with the CIITA construct. Mechanistically, CIITA inhibited HBV transcription and replication by suppressing the activity of HBV-specific enhancers/promoters. Indeed, CIITA exerts antiviral activity in hepatocytes through ERK1/2-mediated down-regulation of the expression of hepatocyte nuclear factor 1α (HNF1α) and HNF4α, which are essential factors for virus replication. In addition, silencing of CIITA significantly abolished the IFN-γ-mediated anti-HBV activity, suggesting that CIITA mediates the anti-HBV activity of IFN-γ to some extent. HBV X protein (HBx) counteracts the antiviral activity of CIITA via direct binding and impairing its function.
Conclusions
Our findings reveal a novel antiviral mechanism of CIITA that involves the modulation of the ERK pathway to restrict HBV transcription. Additionally, our results suggest the possibility of a new immune avoidance mechanism involving HBx.

Citations

Citations to this article as recorded by  Crossref logo
  • Impact of VHSV on CIITA-mediated MHCII expression and antigen presentation in largemouth bass
    Xiaobing Lu, Ziling Qin, Zhe Hu, Hao Huang, Jie Su, Xiaoru Zhang, Meisheng Yi, Kuntong Jia
    Fish & Shellfish Immunology.2025; 162: 110336.     CrossRef
  • Viral oncogenesis in cancer: from mechanisms to therapeutics
    Qing Xiao, Yi Liu, Tingting Li, Chaoyu Wang, Sanxiu He, Liuyue Zhai, Zailin Yang, Xiaomei Zhang, Yongzhong Wu, Yao Liu
    Signal Transduction and Targeted Therapy.2025;[Epub]     CrossRef
  • Bioinformatics and system biology approach to discover the common pathogenetic processes between COVID-19 and chronic hepatitis B
    Xiao Ma, Tengda Huang, Yujia Song, Hongyuan Pan, Ao Du, Xinyi Zhou, Yong Zeng, Kefei Yuan, Xiaosheng Tan
    PLOS One.2025; 20(5): e0323708.     CrossRef
  • Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells
    Enis Kostallari, Robert F. Schwabe, Adrien Guillot
    Cellular & Molecular Immunology.2025; 22(10): 1205.     CrossRef
  • Gender-specific alteration of steroid metabolism and its impact on viral replication in a mouse model of hepatitis B virus infection
    Eun-Sook Park, Juhee Won, Sung Hyun Ahn, Ah Ram Lee, Donghyo Lee, Ju-Yeon Moon, Man Ho Choi, Kyun-Hwan Kim
    Animal Cells and Systems.2024; 28(1): 466.     CrossRef
  • Class II transactivator restricts viral replication, extending its effect to HBV: Editorial on “Novel role of MHC class II transactivator in hepatitis B virus replication and viral counteraction”
    Cho-Rong Lee, Sung-Gyoo Park
    Clinical and Molecular Hepatology.2024; 30(4): 724.     CrossRef
  • Chronic Hepatitis B Genotype C Mouse Model with Persistent Covalently Closed Circular DNA
    Deok-Hwa Seo, Wonhee Hur, Juhee Won, Ji-Won Han, Seung-Kew Yoon, Songmee Bae, Kyun-Hwan Kim, Pil-Soo Sung
    Viruses.2024; 16(12): 1890.     CrossRef
  • 7,077 View
  • 296 Download
  • 10 Web of Science
  • Crossref

Viral hepatitis

Extrahepatic malignancies and antiviral drugs for chronic hepatitis B: A nationwide cohort study
Moon Haeng Hur, Dong Hyeon Lee, Jeong-Hoon Lee, Mi-Sook Kim, Jeayeon Park, Hyunjae Shin, Sung Won Chung, Hee Jin Cho, Min Kyung Park, Heejoon Jang, Yun Bin Lee, Su Jong Yu, Sang Hyub Lee, Yong Jin Jung, Yoon Jun Kim, Jung-Hwan Yoon
Clin Mol Hepatol 2024;30(3):500-514.
Published online May 10, 2024
DOI: https://doi.org/10.3350/cmh.2024.0055
Background/Aims
Chronic hepatitis B (CHB) is related to an increased risk of extrahepatic malignancy (EHM), and antiviral treatment is associated with an incidence of EHM comparable to controls. We compared the risks of EHM and intrahepatic malignancy (IHM) between entecavir (ETV) and tenofovir disoproxil fumarate (TDF) treatment.
Methods
Using data from the National Health Insurance Service of Korea, this nationwide cohort study included treatment-naïve CHB patients who initiated ETV (n=24,287) or TDF (n=29,199) therapy between 2012 and 2014. The primary outcome was the development of any primary EHM. Secondary outcomes included overall IHM development. E-value was calculated to assess the robustness of results to unmeasured confounders.
Results
The median follow-up duration was 5.9 years, and all baseline characteristics were well balanced after propensity score matching. EHM incidence rate differed significantly between within versus beyond 3 years in both groups (P<0.01, Davies test). During the first 3 years, EHM risk was comparable in the propensity score-matched cohort (5.88 versus 5.84/1,000 person-years; subdistribution hazard ratio [SHR]=1.01, 95% confidence interval [CI]=0.88–1.17, P=0.84). After year 3, however, TDF was associated with a significantly lower EHM incidence compared to ETV (4.92 versus 6.91/1,000 person-years; SHR=0.70, 95% CI=0.60–0.81, P<0.01; E-value for SHR=2.21). Regarding IHM, the superiority of TDF over ETV was maintained both within (17.58 versus 20.19/1,000 person-years; SHR=0.88, 95% CI=0.81–0.95, P<0.01) and after year 3 (11.45 versus 16.20/1,000 person-years; SHR=0.68, 95% CI=0.62–0.75, P<0.01; E-value for SHR=2.30).
Conclusions
TDF was associated with approximately 30% lower risks of both EHM and IHM than ETV in CHB patients after 3 years of antiviral therapy.

Citations

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  • Chronic hepatitis B, extrahepatic malignancies and the use of antiviral drugs
    Meng-Che Wu, Shih-Chi Yang, Shuo-Yan Gau
    Clinical and Molecular Hepatology.2025; 31(1): e19.     CrossRef
  • The critical role of ferroptosis in virus-associated hematologic malignancies and its potential value in antiviral-antitumor therapy
    Miao Miao, Yuelei Chen, Xuehan Wang, Shengyang Li, Rong Hu
    Virulence.2025;[Epub]     CrossRef
  • Antiviral Therapy Reduces Dyslipidemia and Cardiovascular Risk in Chronic Hepatitis B: TDF as the Most Effective Agent
    Hyuk Kim, Jae‐Young Kim, Hyun Bin Choi, Ji‐Soo Lee, Yoon E. Shin, Jeong‐Ju Yoo, Sang Gyune Kim, Young‐Seok Kim
    Journal of Medical Virology.2025;[Epub]     CrossRef
  • Characteristics and outcomes in atorvastatin therapy for chronic subdural hematoma: a national, observational real-world study in China, 2019–2024
    Tao Liu, Zhihao Zhao, Jiao Wang, Xiaoying Chen, Jinhao Huang, Weiwei Jiang, Yunhu Yu, Xide Zhu, Kaijie Wang, Kun Lin, Hu Qin, Baixiang Peng, Guohe Zhang, Zhiyong Liu, Weiliang Chen, Jun Shen, Baozhi Chen, Shengjie Li, Mingqi Liu, Wanqiang Su, Wanhai Ding,
    The Lancet Regional Health - Western Pacific.2025; 63: 101688.     CrossRef
  • Association between atherogenic index of plasma and incident aortic disease: a population-based prospective analysis
    Cuihong Tian, Xiao Wang, Liang Tao, Wanyi Wei, Xuan Zhang, Haoxian Tang, Yequn Chen, Xuerui Tan
    Open Heart.2025; 12(2): e003511.     CrossRef
  • 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
    Clinical and Molecular Hepatology.2024; 30(4): 718.     CrossRef
  • Effect of SARS-CoV-2 infection on liver function in patients with hepatitis B
    Tong Sun, Hongbo Chi, Jing Wang, Yufen Zheng, Hongguo Zhu, Jingxian Zhao, Kai Zhou, Mengyuan Chen, Donglian Wang, Tao-Hsin Tung, Jiaqin Xu, Bo Shen
    BMC Infectious Diseases.2024;[Epub]     CrossRef
  • 6,725 View
  • 220 Download
  • 6 Web of Science
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Letter to the Editor

Viral hepatitis

Functional cure of chronic hepatitis B encounters resmetirom
Nai-Bin Yang, Wai-Kay Seto, Ming-Hua Zheng
Clin Mol Hepatol 2024;30(3):580-581.
Published online April 30, 2024
DOI: https://doi.org/10.3350/cmh.2024.0301

Citations

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    Khushi Dahiya, Mahesh Palkar, Sanjay Sharma
    Naunyn-Schmiedeberg's Archives of Pharmacology.2025; 398(8): 9703.     CrossRef
  • Dawn of an era of effective treatments for MAFLD
    Cameron Gofton, Jacob George
    Portal Hypertension & Cirrhosis.2024; 3(4): 206.     CrossRef
  • 5,454 View
  • 124 Download
  • 2 Web of Science
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