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"Jia-Horng Kao"

Correspondence

SAFE Score in Chronic Liver Diseases: A Tool for Risk Enrichment and Personalized Surveillance
Tung-Hung Su, Jia-Horng Kao
Received August 25, 2025  Accepted August 29, 2025  Published online September 1, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0940    [Accepted]
  • 1,354 View
  • 19 Download

Editorial

Breaking the Chain of Perinatal Hepatitis B Transmission
Shang-Chin Huang, Jia-Horng Kao
Received July 20, 2025  Accepted July 24, 2025  Published online July 28, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0801    [Accepted]
  • 1,378 View
  • 11 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
  • 3,479 View
  • 183 Download
  • Crossref

Reply to Correspondence

Advancing metabolic risk profiling in chronic hepatitis B: Reply to correspondence on “Metabolic health in antiviral era of chronic hepatitis B”
Shang-Chin Huang, Jia-Horng Kao
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]
  • 2,769 View
  • 19 Download

Editorial

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]
  • 3,186 View
  • 34 Download

Correspondence

HCC predictors in routine practice for patients with chronic liver diseases: Correspondence to editorial on “High SAFE scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic dysfunction associated steatotic liver disease”
Tung-Hung Su, Jia-Horng Kao
Received February 18, 2025  Accepted February 22, 2025  Published online February 26, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0187    [Epub ahead of print]
  • 2,926 View
  • 15 Download

Original Article

Direct-acting antiviral therapy for patients with hepatitis C virus-related hepatocellular carcinoma: A nationwide cohort study
Shou-Wu Lee, Sheng-Shun Yang, Pei-Chien Tsai, Chung-Feng Huang, Chi-Yi Chen, Chao-Hung Hung, Chien-Hung Chen, Chi-Ming Tai, Pin-Nan Cheng, Hsing-Tao Kuo, Kuo-Chih Tseng, Lein-Ray Mo, Ching-Chu Lo, Yi-Hsiang Huang, Han-Chieh Lin, Pei-Lun Lee, Ming-Jong Bair, Te-Sheng Chang, Chun-Yen Lin, Szu-Jen Wang, Tsai-Yuan Hsieh, Tzeng-Hue Yang, Cheng-Yuan Peng, Chi-Chieh Yang, Lee-Won Chong, Chien-Wei Huang, Chih-Wen Lin, Cheng-Hsin Chu, Ming-Chang Tsai, Jia-Horng Kao, Chun-Jen Liu, Wan-Long Chuang, Teng-Yu Lee, Ming-Lung Yu, on behalf of TACR investigators
Clin Mol Hepatol 2025;31(3):899-913.
Published online February 5, 2025
DOI: https://doi.org/10.3350/cmh.2024.1015
Background/Aims
The survival benefit of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection in patients with hepatocellular carcinoma (HCC), particularly in Barcelona Clinic Liver Cancer (BCLC) stages B/C, remains largely uncertain. We aimed to explore the impact of DAA therapy on overall survival (OS) in HCC patients using a nationwide cohort study.
Methods
We utilized the nationwide Taiwan Association for the Study of the Liver (TASL) HCV Registry (TACR) database to include all adults receiving a DAA therapy for HCV, excluding those with other viral infections, liver transplantation, non-HCC malignancies, and terminal-staged HCC. We respectively analyzed the adjusted odds ratio (aOR) for sustained virological response (SVR) and adjusted hazard ratio (aHR) for OS.
Results
Between December 2013 and December 2020, 2,205 (9.3%) patients with HCC and 21,569 (90.7%) patients without HCC were include. The SVR rates were 96.6% in the HCC group and 98.8% in the non-HCC group (P<0.001), with HCC being an independent risk factor affecting SVR (aOR 0.41; 95% CI 0.31–0.54; P<0.001). In the whole patient cohort, SVR was independently associated with improved OS (aHR 0.46; 95% CI 0.35–0.60; P<0.001). Among patients with baseline HCC, SVR remained an independent factor related to OS (aHR 0.41; 95% CI 0.28–0.59; P<0.001). The impact of SVR on OS persisted significantly across BCLC stages 0/A and stages B/C.
Conclusions
High SVR rates among HCC patients underscore the importance of DAA therapy in enhancing OS, reaffirming its efficacy across various HCC stages.

Citations

Citations to this article as recorded by  Crossref logo
  • Survival impact of hepatitis C virus eradication in patients with or without active hepatocellular carcinoma: A nationwide cohort study
    Teng-Yu Lee, Sheng-Shun Yang, Pei-Chien Tsai, Chung-Feng Huang, Chi-Yi Chen, Chao-Hung Hung, Chien-Hung Chen, Chi-Ming Tai, Pin-Nan Cheng, Hsing-Tao Kuo, Kuo-Chih Tseng, Lein-Ray Mo, Ching-Chu Lo, Yi-Hsiang Huang, Han-Chieh Lin, Pei-Lun Lee, Ming-Jong Bai
    European Journal of Cancer.2026; 232: 116109.     CrossRef
  • Revisiting unmet needs in clinical research on direct-acting antiviral therapy for HCC patients
    Teng-Yu Lee, Pei-Chien Tsai, Shou-Wu Lee, Ming- Lung Yu
    Clinical and Molecular Hepatology.2025;[Epub]     CrossRef
  • Emerging evidence supports direct-acting antiviral therapy for HCC patients beyond the early stage
    Teng-Yu Lee, Pei-Chien Tsai, Shou-Wu Lee, Ming- Lung Yu
    Clinical and Molecular Hepatology.2025;[Epub]     CrossRef
  • HIV, Viral Hepatitis, and Schistosomiasis Association with Liver Cancer: A Systematic Review
    Khumbuzile Canham, Pragalathan Naidoo, Sibusiso Senzani, Sayed Shakeel Kader, Zilungile L. Mkhize-Kwitshana
    Microorganisms.2025; 13(12): 2753.     CrossRef
  • 10,050 View
  • 205 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
  • 11,734 View
  • 550 Download
  • 4 Web of Science
  • Crossref

Original Articles

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.
  • 9,631 View
  • 355 Download

Viral hepatitis

Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy
Pei-Chien Tsai, Chung-Feng Huang, Ming-Lun Yeh, Meng-Hsuan Hsieh, Hsing-Tao Kuo, Chao-Hung Hung, Kuo-Chih Tseng, Hsueh-Chou Lai, Cheng-Yuan Peng, Jing-Houng Wang, Jyh-Jou Chen, Pei-Lun Lee, Rong-Nan Chien, Chi-Chieh Yang, Gin-Ho Lo, Jia-Horng Kao, Chun-Jen Liu, Chen-Hua Liu, Sheng-Lei Yan, Chun-Yen Lin, Wei-Wen Su, Cheng-Hsin Chu, Chih-Jen Chen, Shui-Yi Tung, Chi‐Ming Tai, Chih-Wen Lin, Ching-Chu Lo, Pin-Nan Cheng, Yen-Cheng Chiu, Chia-Chi Wang, Jin-Shiung Cheng, Wei-Lun Tsai, Han-Chieh Lin, Yi-Hsiang Huang, Chi-Yi Chen, Jee-Fu Huang, Chia-Yen Dai, Wan-Long Chung, Ming-Jong Bair, Ming-Lung Yu, T-COACH Study Group
Clin Mol Hepatol 2024;30(3):468-486.
Published online April 19, 2024
DOI: https://doi.org/10.3350/cmh.2024.0038
Background/Aims
Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients.
Methods
We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development.
Results
Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients.
Conclusions
Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Citations

Citations to this article as recorded by  Crossref logo
  • Polypyridyl biguanide ruthenium complex induces photodynamic membrane damage, ferroptosis-like bacterial death, and “bubbling cell death”
    Jincan Chen, Jie Gao, Liang Hao, Qing Guo, Xiang Chen, Fengkai Cai, Zhiyi Li, Jia Zheng, Xufeng Zhu, Lanmei Chen
    Journal of Inorganic Biochemistry.2026; 274: 113110.     CrossRef
  • Prevention of liver cancer in the era of next-generation antivirals and obesity epidemic
    Hiroyuki Suzuki, Naoto Fujiwara, Amit G. Singal, Thomas F. Baumert, Raymond T. Chung, Takumi Kawaguchi, Yujin Hoshida
    Hepatology.2025;[Epub]     CrossRef
  • Reply to the comment on “High-normal and abnormal alanine transaminase levels linked to increased risk of hepatoma following treatment for chronic hepatitis C”
    Yen-Chun Chen, Ming-Lung Yu
    Journal of the Formosan Medical Association.2025;[Epub]     CrossRef
  • Beyond the Liver: A Comprehensive Review of Strategies to Prevent Hepatocellular Carcinoma
    Natchaya Polpichai, Sakditad Saowapa, Pojsakorn Danpanichkul, Shu-Yen Chan, Leandro Sierra, Johanna Blagoie, Chitchai Rattananukrom, Pimsiri Sripongpun, Apichat Kaewdech
    Journal of Clinical Medicine.2024; 13(22): 6770.     CrossRef
  • Metabolic Dysfunction-Associated Steatotic Liver Disease in Chronic Hepatitis C Virus Infection: From Basics to Clinical and Nutritional Management
    Karina Gonzalez-Aldaco, Luis A. Torres-Reyes, Claudia Ojeda-Granados, Leonardo Leal-Mercado, Sonia Roman, Arturo Panduro
    Clinics and Practice.2024; 14(6): 2542.     CrossRef
  • Diverting hepatic lipid fluxes with lifestyles revision and pharmacological interventions as a strategy to tackle steatotic liver disease (SLD) and hepatocellular carcinoma (HCC)
    Davide Misceo, Gabriele Mocciaro, Simona D’Amore, Michele Vacca
    Nutrition & Metabolism.2024;[Epub]     CrossRef
  • 8,992 View
  • 217 Download
  • 11 Web of Science
  • Crossref

Viral hepatitis

Artificial intelligence predicts direct-acting antivirals failure among hepatitis C virus patients: A nationwide hepatitis C virus registry program
Ming-Ying Lu, Chung-Feng Huang, Chao-Hung Hung, Chi‐Ming Tai, Lein-Ray Mo, Hsing-Tao Kuo, Kuo-Chih Tseng, Ching-Chu Lo, Ming-Jong Bair, Szu-Jen Wang, Jee-Fu Huang, Ming-Lun Yeh, Chun-Ting Chen, Ming-Chang Tsai, Chien-Wei Huang, Pei-Lun Lee, Tzeng-Hue Yang, Yi-Hsiang Huang, Lee-Won Chong, Chien-Lin Chen, Chi-Chieh Yang, Sheng‐Shun Yang, Pin-Nan Cheng, Tsai-Yuan Hsieh, Jui-Ting Hu, Wen-Chih Wu, Chien-Yu Cheng, Guei-Ying Chen, Guo-Xiong Zhou, Wei-Lun Tsai, Chien-Neng Kao, Chih-Lang Lin, Chia-Chi Wang, Ta-Ya Lin, Chih‐Lin Lin, Wei-Wen Su, Tzong-Hsi Lee, Te-Sheng Chang, Chun-Jen Liu, Chia-Yen Dai, Jia-Horng Kao, Han-Chieh Lin, Wan-Long Chuang, Cheng-Yuan Peng, Chun-Wei- Tsai, Chi-Yi Chen, Ming-Lung Yu, TACR Study Group
Clin Mol Hepatol 2024;30(1):64-79.
Published online November 21, 2023
DOI: https://doi.org/10.3350/cmh.2023.0287
Background/Aims
Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy.
Methods
We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment.
Results
The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset.
Conclusions
Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Citations

Citations to this article as recorded by  Crossref logo
  • AI-Safe-C score: Assessing liver-related event risks in patients without cirrhosis after successful direct-acting antiviral treatment
    Huapeng Lin, Terry Cheuk-Fung Yip, Hye Won Lee, Xiangjun Meng, Jimmy Che-To Lai, Sang Hoon Ahn, Wenjing Pang, Grace Lai-Hung Wong, Lingfeng Zeng, Vincent Wai-Sun Wong, Victor de Lédinghen, Seung Up Kim
    Journal of Hepatology.2025; 82(3): 456.     CrossRef
  • Real‐world efficacy and safety of universal 8‐week glecaprevir/pibrentasvir in patients with chronic hepatitis C with early chronic kidney disease or pre‐end‐stage renal disease: Insights from a nationwide hepatisis C virus registry in Taiwan
    Szu‐Jen Wang, Chung‐Feng Huang, Te‐Sheng Chang, Ching‐Chu Lo, Chao‐Hung Hung, Chien‐Wei Huang, Lee‐Won Chong, Pin‐Nan Cheng, Ming‐Lun Yeh, Cheng‐Yuan Peng, Chien‐Yu Cheng, Jee‐Fu Huang, Ming‐Jong Bair, Chih‐Lang Lin, Chi‐Chieh Yang, Hsing‐Tao Kuo, Tsai‐Yu
    The Kaohsiung Journal of Medical Sciences.2025;[Epub]     CrossRef
  • Mitochondrial mt12361A>G increased risk of metabolic dysfunction-associated steatotic liver disease among non-diabetes
    Ming-Ying Lu, Yu-Ju Wei, Chih-Wen Wang, Po-Cheng Liang, Ming-Lun Yeh, Yi-Shan Tsai, Pei-Chien Tsai, Yu-Min Ko, Ching-Chih Lin, Kuan-Yu Chen, Yi-Hung Lin, Tyng-Yuan Jang, Ming-Yen Hsieh, Zu-Yau Lin, Chung-Feng Huang, Jee-Fu Huang, Chia-Yen Dai, Wan-Long Ch
    World Journal of Gastroenterology.2025;[Epub]     CrossRef
  • Explainable machine learning for the assessment of donor grafts in liver transplantation
    Liang Zhixing, Ye Linsen, Jiang Peng, Dong Siyi, Yu Haoyuan, Li Kun, Li Siqi, Hu Yongwei, Zhang Mingshen, Liu Wei, Li Hua, Yi Shuhong, Chen Guihua, Xu Xiao, Zheng Shusen, Yang Yang
    Hepatology Research.2025; 55(6): 908.     CrossRef
  • Role of risk factors and their variable types in predicting noise-induced hearing loss using artificial intelligence algorithms
    Zhengheng Zhang, Longteng Jiang, Meibian Zhang, Yuan Pan, Jinnan Zheng, Anqi Liu, Weijiang Hu, Xin Jin
    Hearing Research.2025; 465: 109353.     CrossRef
  • Artificial Intelligence and Machine Learning Applications in Liver Disease
    Bhargav Vemulapalli, Meghana Ghattu, Kavya Atluri, James Lee, Vinod Rustgi
    Clinics in Liver Disease.2025; 29(4): 755.     CrossRef
  • Unveiling the nexus between direct-acting antivirals in hepatitis C virus elimination and immune response
    Aya I. Abdelaziz, Eman Abdelsameea, Sara A. Wahdan, Doaa Elsherbiny, Zeinab Zakaria, Samar S. Azab
    Clinical and Experimental Medicine.2025;[Epub]     CrossRef
  • Hepatitis C Virus: Epidemiological Challenges and Global Strategies for Elimination
    Daniela Toma, Lucreția Anghel, Diana Patraș, Anamaria Ciubară
    Viruses.2025; 17(8): 1069.     CrossRef
  • Nationwide hepatitis C virus microelimination in uremic patients undergoing maintenance hemodialysis in Taiwan
    Chung-Feng Huang, Po-Cheng Liang, Yu-Ju Wei, Chao-Chun Wu, Shi-Lun Wei, Li-Ju Lin, Pei-Chun Hsieh, Tsui-Hsia Hsu, Maggie Shu-Mei Hsu, Ya-Xin Luo, Hsi-Chieh Chen, Tsu-Yun Ho, Shao-Hsuan Lin, Chia-Ling Liu, Kuo-Pen Cheng, John W. Ward, Ming-Lung Yu
    Journal of the Formosan Medical Association.2025;[Epub]     CrossRef
  • Identifying new strategies to combat cytomegalovirus by integrating existing and innovative approaches in diagnosis and treatment
    Nargiz Imamova, Ayten Feteliyeva, Adil M. Allahverdiyev
    Future Virology.2025; 20(10): 379.     CrossRef
  • Artificial intelligence in hepatology: A comprehensive scoping review of clinical applications, challenges, and future directions
    Kirolos Eskandar
    iLIVER.2025; 4(4): 100205.     CrossRef
  • Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan
    Chin-Wei Chang, Wei-Fan Hsu, Kuo-Chih Tseng, Chi-Yi Chen, Pin-Nan Cheng, Chao-Hung Hung, Ching-Chu Lo, Ming-Jong Bair, Chien-Hung Chen, Pei-Lun Lee, Chun-Yen Lin, Hsing-Tao Kuo, Chun-Ting Chen, Chi-Chieh Yang, Jee-Fu Huang, Chi-Ming Tai, Jui-Ting Hu, Chih
    Digestive Diseases and Sciences.2024; 69(9): 3501.     CrossRef
  • Bridging Real-World Data Gaps: Connecting Dots Across 10 Asian Countries
    Guilherme Silva Julian, Wen-Yi Shau, Hsu-Wen Chou, Sajita Setia
    JMIR Medical Informatics.2024; 12: e58548.     CrossRef
  • The role of artificial intelligence in the management of liver diseases
    Ming‐Ying Lu, Wan‐Long Chuang, Ming‐Lung Yu
    The Kaohsiung Journal of Medical Sciences.2024; 40(11): 962.     CrossRef
  • Real-World Experience, Effectiveness, and Safety of Direct-Acting Antivirals for the Treatment of Hepatitis C in Oman: A Cross-Sectional, Multicenter Study
    Khalid M. Al-Naamani, Heba Omar, Said A. Al Busafi, Halima H. Al Shuaili, Zakariya Al-Naamani, Murtadha Al-Khabori, Elias A. Said, Abdullah H. AlKalbani, B. R. Kamath, Bashar Emad, Shahina Daar, Lolo Alhajri, Alya AlKalbani, Zainab AlFarsi, Haifa Alzuhaib
    Journal of Clinical Medicine.2024; 13(23): 7411.     CrossRef
  • 11,262 View
  • 197 Download
  • 17 Web of Science
  • Crossref

Reviews

Steatotic liver disease

Taiwan Association for the Study of the Liver-Taiwan Society of Cardiology Taiwan position statement for the management of metabolic dysfunction- associated fatty liver disease and cardiovascular diseases
Pin-Nan Cheng, Wen-Jone Chen, Charles Jia-Yin Hou, Chih-Lin Lin, Ming-Ling Chang, Chia-Chi Wang, Wei-Ting Chang, Chao-Yung Wang, Chun-Yen Lin, Chung-Lieh Hung, Cheng-Yuan Peng, Ming-Lung Yu, Ting-Hsing Chao, Jee-Fu Huang, Yi-Hsiang Huang, Chi-Yi Chen, Chern-En Chiang, Han-Chieh Lin, Yi-Heng Li, Tsung-Hsien Lin, Jia-Horng Kao, Tzung-Dau Wang, Ping-Yen Liu, Yen-Wen Wu, Chun-Jen Liu
Clin Mol Hepatol 2024;30(1):16-36.
Published online October 4, 2023
DOI: https://doi.org/10.3350/cmh.2023.0315
Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.

Citations

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  • A machine learning model to predict liver-related outcomes after the functional cure of chronic hepatitis B
    Moon Haeng Hur, Terry Cheuk-Fung Yip, Seung Up Kim, Hyun Woong Lee, Han Ah Lee, Hyung-Chul Lee, Grace Lai-Hung Wong, Vincent Wai-Sun Wong, Jun Yong Park, Sang Hoon Ahn, Beom Kyung Kim, Hwi Young Kim, Yeon Seok Seo, Hyunjae Shin, Jeayeon Park, Yunmi Ko, Yo
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  • Reply to: “A machine learning model to predict liver-related outcomes after the functional cure of chronic hepatitis B: Is cirrhosis driving the performance?”
    Moon Haeng Hur, Jeong-Hoon Lee
    Journal of Hepatology.2025; 82(3): e143.     CrossRef
  • Metabolic dysfunction‐associated steatotic liver disease is associated with increased risks of heart failure
    Kai‐Chun Chang, Tung‐Hung Su, Cho‐Kai Wu, Shang‐Chin Huang, Tai‐Chung Tseng, Chun‐Ming Hong, Shih‐Jer Hsu, Chen‐Hua Liu, Hung‐Chih Yang, Chun‐Jen Liu, Jia‐Horng Kao
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  • Metabolic dysfunction-associated steatotic liver disease and its associated health risks
    Xia-Rong Liu, Szu-Ching Yin, Yi-Ting Chen, Mei-Hsuan Lee
    Journal of the Chinese Medical Association.2025; 88(5): 343.     CrossRef
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    Jui-Hua Huang, Ren-Hau Li, Hon-Ke Sia, Feng-Cheng Tang
    Metabolites.2025; 15(5): 318.     CrossRef
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    Shaojie Duan, Mengdie Chen, Jie Chen, Yaojian Shao, Xiaolong Jin, Chaohui Wang, Ping Feng, Xiaosheng Teng, Zhenjun Yu
    European Journal of Gastroenterology & Hepatology.2025; 37(10): 1155.     CrossRef
  • The role of Bergamot Polyphenolic Fraction (BPF) in MASLD-Induced HFpEF: Mitigate diastolic dysfunction by targeting chronic low-grade inflammation
    Cristina Carresi, Antonio Cardamone, Vincenzo Musolino, Rocco Mollace, Annamaria Tavernese, Anna Rita Coppoletta, Micaela Gliozzi, Vincenzo Mollace
    Biomedicine & Pharmacotherapy.2025; 190: 118375.     CrossRef
  • FIB‐4 Serves as a Referral Index for Coronary Artery Calcification in Patients With MASLD
    Ya‐Chin Huang, Chih‐Wen Wang, Jiun‐Chi Huang, Po‐Cheng Liang, Ming‐Lun Yeh, Yi‐Yu Chen, Yi‐Hung Lin, Tyng‐Yuan Jang, Yu‐Ju Wei, Ming‐Yen Hsieh, Chao‐Kuan Huang, Hsu‐Han Chien, Chia‐Jen Wu, Jee‐Fu Huang, Chia‐Yen Dai, Wan‐Long Chuang, Chia‐I Lin, Chung‐Fen
    Journal of Gastroenterology and Hepatology.2025;[Epub]     CrossRef
  • Cardiovascular risk of tenofovir disoproxil fumarate or tenofovir alafenamide in patients with chronic hepatitis B: More questions than an answer
    Pin-Nan Cheng, Ming-Lung Yu
    Clinical and Molecular Hepatology.2024; 30(2): 144.     CrossRef
  • MAFLD: from a disease framework to patient care
    Mohammed Eslam, Jacob George
    Hepatology International.2024; 18(S2): 823.     CrossRef
  • Effect of metabolic dysfunction on the risk of liver-related events in patients cured of hepatitis C virus
    Wei-Fan Hsu
    American Journal of Cancer Research.2024; 14(4): 1914.     CrossRef
  • The unfolded features on the synchronized fashion of gut microbiota and Drynaria rhizome against obesity via integrated pharmacology
    Ki-Kwang Oh, Sang-Jun Yoon, Seol Hee Song, Jeong Ha Park, Jeong Su Kim, Min Ju Kim, Dong Joon Kim, Ki-Tae Suk
    Food Chemistry.2024; 460: 140616.     CrossRef
  • High sensitivity troponins and mortality in the population with metabolic dysfunction-associated steatotic liver disease
    Jingjing Hu, Yuteng Du, Yidan Zhou, Huiying Wang
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    Zong-Long Li, Jia-Lu Chen, Yue Tang, De-Long Qin, Zhao-Hui Tang
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  • Metabolic dysfunction-associated fatty liver disease: bridging cardiology and hepatology
    Xiao-Dong Zhou, Giovanni Targher, Christopher D. Byrne, Michael D. Shapiro, Li-Li Chen, Ming-Hua Zheng
    Cardiology Plus.2024; 9(4): 275.     CrossRef
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  • 375 Download
  • 19 Web of Science
  • Crossref

Viral hepatitis

Safety considerations for withdrawal of nucleos(t)ide analogues in patients with chronic hepatitis B: First, do no harm
Yao-Chun Hsu, Cheng-Hao Tseng, Jia-Horng Kao
Clin Mol Hepatol 2023;29(4):869-890.
Published online March 14, 2023
DOI: https://doi.org/10.3350/cmh.2022.0420
Nucleos(t)ide analogues (NA) are widely used to treat hepatitis B virus (HBV) infection, but they cannot eradicate the virus and treatment duration can be lifelong if the endpoint is set at seroclearance of the hepatitis B surface antigen (HBsAg). As an alternative strategy, finite NA therapy without the prerequisite of HBsAg seroclearance has been proposed to allow treatment cessation in patients with sustained undetectable HBV viremia for two to three years. However, reactivation of viral replication almost always follows NA withdrawal. Whereas HBV reactivation might facilitate HBsAg seroclearance in some, it could lead to serious acute flare-ups in a certain proportion of patients. Occurrence and consequences of NA withdrawal flares are complicated with various factors involving the virus, host, and treatment. Accurate risk prediction for severe flares following NA cessation is essential to ensure patient safety. The risks of life-threatening flares in patients who discontinued NA according to the stopping rules of current guidelines or local reimbursement policies have recently been quantitatively estimated in large-scale studies, which also provided empirical evidence to help identify vulnerable patients at risk of devastating outcomes. Moreover, risk predictors were further explored and validated to hopefully aid in patient selection and management. In this narrative review with a focus on patient safety, we summarize and discuss current literature on the incidence of severe flares following NA cessation, risk stratification for candidate selection, rules of posttreatment monitoring, and indications for treatment resumption. We also share our thoughts on the limitations of existing knowledge and suggestions for future research.

Citations

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  • Nucleos(t)ide Analog Treatment Discontinuation in Chronic Hepatitis B Virus Infection: A Systematic Literature Review
    Robert Gish, Kosh Agarwal, Anadi Mahajan, Supriya Desai, Saifuddin Kharawala, Rob Elston, Joyeta Das, Stuart Kendrick, Vera Gielen
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  • Editorial: The Relevance of Hepatic Flares and Quantitative Hepatitis B Surface Antigen After Stopping HBV Polymerase Inhibitors—Authors' Reply
    Ying‐Nan Tsai, Jia‐Ling Wu, Yao‐Chun Hsu
    Alimentary Pharmacology & Therapeutics.2025; 61(7): 1244.     CrossRef
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    Ying‐Nan Tsai, Jia‐Ling Wu, Cheng‐Hao Tseng, Shang‐Chen Tseng, Chih‐Lung Hung, Mindie H. Nguyen, Jaw‐Town Lin, Yao‐Chun Hsu
    Alimentary Pharmacology & Therapeutics.2025; 61(7): 1208.     CrossRef
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    Ying‐Nan Tsai, Yao‐Chun Hsu
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    Chih-Lin Lin, Jia-Horng Kao
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    Ying‐Nan Tsai, Jia‐Ling Wu, Yao‐Chun Hsu
    Alimentary Pharmacology & Therapeutics.2024; 59(1): 136.     CrossRef
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    Ying-Nan Tsai, Jia-Ling Wu, Yao-Chun Hsu
    Clinical and Molecular Hepatology.2024; 30(2): 276.     CrossRef
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    Chen-Te Huang, Tai-Chung Tseng
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    Yao-Chun Hsu
    Clinical Liver Disease.2024;[Epub]     CrossRef
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    Daisuke Usuda, Yuki Kaneoka, Rikuo Ono, Masashi Kato, Yuto Sugawara, Runa Shimizu, Tomotari Inami, Eri Nakajima, Shiho Tsuge, Riki Sakurai, Kenji Kawai, Shun Matsubara, Risa Tanaka, Makoto Suzuki, Shintaro Shimozawa, Yuta Hotchi, Ippei Osugi, Risa Katou,
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    Marina Manea, Ion Mărunțelu, Ileana Constantinescu
    Frontiers in Medicine.2024;[Epub]     CrossRef
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    Stephen Sinclair, Sean Shearen, Youssef Ghobrial, George Trad, Syed Abdul Basit, David Shih, John K. Ryan
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    Jie Wang, He Jiang, Guoqi Zhang, Xiahong Dai, Hainv Gao, Lanjuan Li
    Journal of Medical Virology.2024;[Epub]     CrossRef
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    Yao‐Chun Hsu, Yi‐Hsian Lin, Teng‐Yu Lee, Mindie H. Nguyen, Cheng‐Hao Tseng, Hsiu J. Ho, Feng‐Yu Kao, Jaw‐Town Lin, Chen‐Yi Wu, Chun‐Ying Wu
    Alimentary Pharmacology & Therapeutics.2023; 58(4): 463.     CrossRef
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    Yao‐Chun Hsu, Chun‐Ying Wu
    Alimentary Pharmacology & Therapeutics.2023; 58(5): 550.     CrossRef
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    Yao‐Chun Hsu, Mindie H. Nguyen, Chun‐Ying Wu
    Alimentary Pharmacology & Therapeutics.2023; 58(7): 733.     CrossRef
  • 8,545 View
  • 242 Download
  • 21 Web of Science
  • Crossref

Viral hepatitis

Acute hepatitis C virus infection: clinical update and remaining challenges
Chen-Hua Liu, Jia-Horng Kao
Clin Mol Hepatol 2023;29(3):623-642.
Published online February 20, 2023
DOI: https://doi.org/10.3350/cmh.2022.0349
Acute hepatitis C virus (HCV) infection is a global health concern with substantial geographical variation in the incidence rate. People who have received unsafe medical procedures, used injection drugs, and lived with human immunodeficiency virus are reported to be most susceptible to acute HCV infection. The diagnosis of acute HCV infection is particularly challenging in immunocompromised, reinfected, and superinfected patients due to difficulty in detecting anti-HCV antibody seroconversion and HCV ribonucleic acid from a previously negative antibody response. With an excellent treatment effect on chronic HCV infection, recently, clinical trials investigating the benefit of direct-acting antivirals (DAAs) treatment for acute HCV infection have been conducted. Based on the results of cost-effectiveness analysis, DAAs should be initiated early in acute HCV infection prior to spontaneous viral clearance. Compared to the standard 8–12 week-course of DAAs for chronic HCV infection, DAAs treatment duration may be shortened to 6–8 weeks in acute HCV infection without compromising the efficacy. Standard DAA regimens provide comparable efficacy in treating HCV-reinfected patients and DAA-naïve ones. For cases contracting acute HCV infection from HCV-viremic liver transplant, a 12-week course of pangenotypic DAAs is suggested. While for cases contracting acute HCV infection from HCV-viremic non-liver solid organ transplants, a short course of prophylactic or pre-emptive DAAs is suggested. Currently, prophylactic HCV vaccines are unavailable. In addition to treatment scale-up for acute HCV infection, practice of universal precaution, harm reduction, safe sex, and vigilant surveillance after viral clearance remain critical in reducing HCV transmission.

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Viral hepatitis

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

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Original Article

Viral hepatitis

Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis
Chen-Hua Liu, Chi-Yi Chen, Wei-Wen Su, Chun-Jen Liu, Ching-Chu Lo, Ke-Jhang Huang, Jyh-Jou Chen, Kuo-Chih Tseng, Chi-Yang Chang, Cheng-Yuan Peng, Yu-Lueng Shih, Chia-Sheng Huang, Wei-Yu Kao, Sheng-Shun Yang, Ming-Chang Tsai, Jo-Hsuan Wu, Po-Yueh Chen, Pei-Yuan Su, Jow-Jyh Hwang, Yu-Jen Fang, Pei-Lun Lee, Chi-Wei Tseng, Fu-Jen Lee, Hsueh-Chou Lai, Tsai-Yuan Hsieh, Chun-Chao Chang, Chung-Hsin Chang, Yi-Jie Huang, Jia-Horng Kao
Clin Mol Hepatol 2021;27(4):575-588.
Published online July 13, 2021
DOI: https://doi.org/10.3350/cmh.2021.0155
Background/Aims
Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited.
Methods
We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported.
Results
The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001).
Conclusions
SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.

Citations

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Review

Viral hepatitis

Three heads are better than two: Hepatitis B core-related antigen as a new predictor of hepatitis B virus-related hepatocellular carcinoma
Jer-Wei Wu, Jia-Horng Kao, Tai-Chung Tseng
Clin Mol Hepatol 2021;27(4):524-534.
Published online February 23, 2021
DOI: https://doi.org/10.3350/cmh.2021.0012
Patients with chronic hepatitis B virus (HBV) infection are at risk of developing hepatocellular carcinoma (HCC), and serum markers reflecting viral replication are potential predictors for HCC development. Besides the levels of serum HBV DNA and hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg) quantification is an emerging serological marker for viral replication. Unlike HBV DNA and HBsAg, HBcrAg is a covalently closed circular DNA-derived protein marker, consisting of hepatitis B e antigen (HBeAg), p22cr, and hepatitis B core antigen. In treatment-naïve HBV patients, higher HBcrAg levels are shown to be associated with an increased risk of HCC in several studies. More importantly, HBcrAg may complement HBV DNA level to predict HCC development. For example, an Asian treatmentnaïve cohort study’s data showed that HBcrAg level of 4 log U/mL was effective to stratify HCC risk in HBeAg-negative patients with intermediate viral loads, who may not need antiviral therapy because of the low to moderate risk of HCC. In patients receiving prolonged nucleos(t)ide analogue with profound viral suppression, most data indicated that HBV DNA and HBsAg levels no longer serve as HCC predictors. However, several studies suggested on-treatment HBcrAg levels may remain as an HCC predictor. In summary, HBcrAg level can be a useful biomarker for treatment-naïve patients, but its value in on-treatment patients needs validation. The next challenge is how to combine HBcrAg with the other viral markers to construct a better HCC prediction model, optimizing the management of HBV patients.

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Original Article

Hepatic neoplasm

Direct comparison of biopsy techniques for hepatic malignancies
Shang-Chin Huang, Ja-Der Liang, Shih-Jer Hsu, Tzu-Chan Hong, Hung-Chih Yang, Jia-Horng Kao
Clin Mol Hepatol 2021;27(2):305-312.
Published online December 3, 2020
DOI: https://doi.org/10.3350/cmh.2020.0301
Background/Aims
The core needle biopsy (CNB), fine needle aspiration cytology (FNAC) and touch imprint cytology (TIC) are commonly used tools for the diagnosis of hepatic malignancies. However, little is known about the benefits and criteria for selecting appropriate technique among them in clinical practice. We aimed to compare the sensitivity of ultrasound-guided CNB, FNAC, TIC as well as combinations for the diagnosis of hepatic malignancies, and to determine the factors associated with better sensitivity in each technique.
Methods
From January 2018 to December 2019, a total of 634 consecutive patients who received ultrasound-guided liver biopsies at the National Taiwan University Hospital was collected, of whom 235 with confirmed malignant hepatic lesions receiving CNB, FNAC and TIC simultaneously were enrolled for analysis. The clinical and procedural data were compared.
Results
The sensitivity of CNB, FNAC and TIC for the diagnosis of malignant hepatic lesions were 93.6%, 71.9%, and 85.1%, respectively. Add-on use of FNAC or TIC to CNB provided additional sensitivity of 2.1% and 0.4%, respectively. FNAC exhibited a significantly higher diagnostic rate in the metastatic cancers (P=0.011), hyperechoic lesions on ultrasound (P=0.028), and those with depth less than 4.5 cm from the site of needle insertion (P=0.036).
Conclusions
The sensitivity of CNB is superior to that of FNAC and TIC for the diagnosis of hepatic malignancies. Nevertheless, for shallow (depth <4.5 cm) and hyperechoic lesions not typical for primary liver cancers, FNAC alone provides excellent sensitivity.

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Reviews

Viral hepatitis

New perspectives of biomarkers for the management of chronic hepatitis B
Chih-Lin Lin, Jia-Horng Kao
Clin Mol Hepatol 2016;22(4):423-431.
Published online December 25, 2016
DOI: https://doi.org/10.3350/cmh.2016.0069
With recent advances in molecular and genomic investigations, the impact of hepatitis B viral and host factors on the progression of chronic HBV infection has been explored. For viral factors, hepatitis B viral load is a strong predictor for liver disease progression. Hepatitis B viral kinetics appear to be important for successful anti-viral therapy. Serum HBsAg level serves as a complementary marker to viral load for the prediction of HBV-related adverse outcomes in patients with low viral load. In those with low viral load, high serum HBsAg level is associated with higher risks of cirrhosis and HCC. Hepatitis B core-related antigen (HBcrAg) induces host immune responses, and the reduction of the HBcrAg level as well as the increment of total anti-HBc level are significantly associated with favorable outcomes. HBV genotypes (genotype C/D) and mutants (basal core promoter and deletion mutation in pre-S genes) are well known viral genetic markers to predict disease progression. For host factors, serum inflammatory biomarkers have been developed to evaluate the HBV-associated hepatic necroinflammation and fibrosis. Host single nucleotide polymorphism on sodium taurocholate cotransporting polypeptide (NTCP, an HBV entry receptor) may be associated with a decreased risk for cirrhosis and HCC. In conclusion, patients with chronic hepatitis B should be evaluated with relevant viral and host markers to identify those who are at a higher risk of liver disease progression and then receive timely antiviral therapy.

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Viral hepatitis

Risk stratification of HBV infection in Asia-Pacific region
Jia-Horng Kao
Clin Mol Hepatol 2014;20(3):223-227.
Published online September 25, 2014
DOI: https://doi.org/10.3350/cmh.2014.20.3.223

Hepatitis B virus (HBV) infection is the major etiology of chronic liver disease worldwide and thus a global health problem, especially in Asia-Pacific region. The long-term outcomes of Asian HBV carriers vary widely; however, a significant proportion of them will finally develop end-stage liver disease. Over the past decade, several host and HBV factors predictive of clinical outcomes in Asian HBV carriers have been identified. The community-based REVEAL-HBV study illustrated the strong association between HBV-DNA level at study entry and risk of HCC over time, and male gender, older age, high serum alanine aminotransferase (ALT) level, positive HBeAg, higher HBV-DNA level, HBV genotype C infection and core promoter mutation are independently associated with a higher hepatocellular carcinoma (HCC) risk. Another hospital-based ERADICATE-B cohort further validated the HCC risk started to increase when HBV-DNA level was higher than 2,000 IU/mL. Of particular note, in patients with low viral load (HBV-DNA level <2,000 IU/mL), HBsAg level ≥1,000 IU/mL was a new independent risk factor for HCC. With the results from REVEAL-HBV study, a risk calculator for predicting HCC in adult non-cirrhotic patients has been developed and validated by independent international cohorts (REACH-B). With the combination of HBV-DNA, HBsAg, and ALT levels, ERADICATE-B study proposed an algorithm to predict disease progression and categorize risk levels of HCC as well as corresponding management in Asian HBV carriers. The introduction of transient elastography may further enhance the predictive power. In conclusion, HBsAg level can complement HBV-DNA level for the risk stratification of disease progression in Asian adult patients with chronic HBV infection.

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