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"Ming-Lung Yu"

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.
Result
s: The study included 4,500 patients. PSM yielded 909 pairs of patients with balanced characteristics. When stratified by the number of metabolic diseases, only patients with ≥2 metabolic diseases had an increased cumulative incidence of cirrhosis and overall death. However, when stratified by the presence of diabetes (regardless of the presence or number of other metabolic diseases), patients with diabetes (versus those without) had a significantly higher cumulative incidence of all outcomes: cirrhosis (P=0.009), hepatocellular carcinoma (HCC, P=0.023), and overall, liver-related, and non-liver-related death (P<0.001, P=0.026 and P<0.001, respectively). Having ≥2 metabolic diseases was associated with cirrhosis, overall death, and non-liver-related death but not HCC or liver-related death, while diabetes was significantly associated with a higher risk of all outcomes: cirrhosis (hazard ratio [HR]=3.75, P=0.004), HCC (HR=2.02, P=0.020), and overall, liver-related, and non-liver-related death (HR=2.53, P<0.001; HR=2.65, P=0.016; HR=2.38, P<0.001).
Conclusions
Having two or more metabolic diseases was associated with a higher risk of cirrhosis, overall death, and non-liver-related death, but having diabetes as a single metabolic disease was significantly associated with all adverse outcomes including cirrhosis, HCC, and overall, liver-related, and non-liver-related death.

Citations

Citations to this article as recorded by  Crossref logo
  • Advancing metabolic risk profiling in chronic hepatitis B: Reply to correspondence on “Metabolic health in antiviral era of chronic hepatitis B”
    Shang-Chin Huang, Jia-Horng Kao
    Clinical and Molecular Hepatology.2026; 32(1): e117.     CrossRef
  • Metabolic health in antiviral era of chronic hepatitis B: Editorial on “Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues”
    Shang-Chin Huang, Jia-Horng Kao
    Clinical and Molecular Hepatology.2026; 32(1): 423.     CrossRef
  • Differential HCC risk among HBV indeterminate types at baseline and by phase transition
    Rui Huang, Huy N Trinh, Satoshi Yasuda, Angela Chau, Mayumi Maeda, Ai-Thien Do, Daniel Q Huang, Takanori Ito, Takashi Honda, Masatoshi Ishigami, Ritsuzo Kozuka, Carmen Monica Preda, Cheng-Hao Tseng, Sebastián Marciano, Pei-Chien Tsai, Dong Hyun Lee, Chris
    Gut.2025; 74(11): 1873.     CrossRef
  • Type 2 diabetes mellitus as an independent predictor of significant fibrosis in treatment-naïve chronic hepatitis B patients with concurrent hepatic steatosis
    Jie Li, Liang Xu, Fajuan Rui, Sally Tran, Pei-Chien Tsai, Youwen Tan, Hidenori Toyoda, Qing-Lei Zeng, Huy Trinh, Yao-Chun Hsu, Tsunamasa Watanabe, Hiroshi Abe, Hiroyuki Motoyama, Yoko Yoshimaru, Takanori Suzuki, Taeang Arai, Masanori Atsukawa, Phillip Vut
    Hepatology.2025;[Epub]     CrossRef
  • Incidence and determinants of achieving HBsAg <100 IU/mL in HBeAg-negative CHB patients with nucleos(t)ide analogue treatment
    Jian Wang, Tao Fan, Zhiyi Zhang, Li Zhu, Shaoqiu Zhang, Ye Xiong, Chun Shan, Chao Jiang, Shengxia Yin, Xin Tong, Renling Yao, Juan Xia, Xiaomin Yan, Yu Shi, Yuxin Chen, Xingxiang Liu, Huali Wang, Haixia Zhang, Chuanwu Zhu, Qun Zhang, Chao Wu, Rui Huang
    Emerging Microbes & Infections.2025;[Epub]     CrossRef
  • Impact of metabolic dysfunction on treatment responses to nucleos(t)ide analogues in chronic hepatitis B: a retrospective multi-center REAL-B cohort study
    Rui Huang, Dae Won Jun, Hidenori Toyoda, Yao-Chun Hsu, Huy Trinh, Akito Nozaki, Toru Ishikawa, Tsunamasa Watanabe, Haruki Uojima, Daniel Q. Huang, Takashi Honda, Yasuhito Tanaka, Philip Vutien, Sebastián Marciano, Hiroshi Abe, Masaru Enomoto, Masanori Ats
    eClinicalMedicine.2025; 87: 103407.     CrossRef
  • Aspirin Use and Risk of HCC and Gastrointestinal Bleeding in Patients With HBV‐Related Cirrhosis: A Landmark Analysis
    Mi Na Kim, Geun U. Park, Seng Chan You, Jae Seung Lee, Hye Won Lee, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn
    Journal of Gastroenterology and Hepatology.2025; 40(11): 2750.     CrossRef
  • Multifunctional Metal Composite Hydrogels for Diabetic Wound Therapy
    Shengnan Zhang, Hui Gao, Kevin H. Mayo, Jingang Mo, Le Deng
    Gels.2025; 11(12): 960.     CrossRef
  • 12,479 View
  • 216 Download
  • 12 Web of Science
  • Crossref

Correspondence

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

Citations

Citations to this article as recorded by  Crossref logo
  • Revisiting unmet needs in clinical research on direct-acting antiviral therapy for HCC patients: Correspondence to letter to the editor on “Direct-acting antiviral therapy for patients with HCV-related hepatocellular carcinoma: A nationwide cohort study”
    Teng-Yu Lee, Pei-Chien Tsai, Shou-Wu Lee, Ming- Lung Yu
    Clinical and Molecular Hepatology.2026; 32(1): e99.     CrossRef
  • Should direct-acting antiviral be considered for all patients with HCV-related hepatocellular carcinoma?: Reply to correspondence on “Direct-acting antiviral therapy for patients with HCV-related hepatocellular carcinoma: A nationwide cohort study”
    Yan Ling Ong, Apichat Kaewdech, Yu Jun Wong
    Clinical and Molecular Hepatology.2026; 32(1): e109.     CrossRef
  • 4,726 View
  • 38 Download
  • 1 Web of Science
  • Crossref

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.
Result
s: 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
  • Revisiting unmet needs in clinical research on direct-acting antiviral therapy for HCC patients: Correspondence to letter to the editor on “Direct-acting antiviral therapy for patients with HCV-related hepatocellular carcinoma: A nationwide cohort study”
    Teng-Yu Lee, Pei-Chien Tsai, Shou-Wu Lee, Ming- Lung Yu
    Clinical and Molecular Hepatology.2026; 32(1): e99.     CrossRef
  • Emerging evidence supports direct-acting antiviral therapy for HCC patients beyond the early stage: Correspondence to editorial on “Direct-acting antiviral therapy for patients with HCV-related hepatocellular carcinoma: A nationwide cohort study”
    Teng-Yu Lee, Pei-Chien Tsai, Shou-Wu Lee, Ming-Lung Yu
    Clinical and Molecular Hepatology.2026; 32(1): e68.     CrossRef
  • 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
  • Letter to the editor on “Direct-acting antiviral therapy for patients with HCV-related hepatocellular carcinoma: a nationwide cohort study”
    Qiong Wang, Zhongqing Qian, Xiaodi Yang, Deyan Chen, Xiaojing Wang, Fuliang Chen
    Clinical and Molecular Hepatology.2026; 32(1): e7.     CrossRef
  • Setting the Record Straight: Utility and Outcomes in Patients With HCV Related HCC
    María Fernanda Guerra‐Veloz, Sital Shah, Beatrice Emmanouil, Mia Olsen, Renita George, Sarah Selemani, Paul J. Ross, Ivana Carey, Neha Mehta, Mark Gillyon‐Powell, Kosh Agarwal
    Journal of Viral Hepatitis.2026;[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
  • 12,673 View
  • 215 Download
  • 8 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

Citations to this article as recorded by  Crossref logo
  • Expanding treatment eligibility for chronic hepatitis B: Balancing benefits, limitations, and healthcare access: Correspondence to editorial on “Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TOR
    Yao-Chun Hsu, Chi-Yi Chen, Jaw-Town Lin
    Clinical and Molecular Hepatology.2025; 31(2): e169.     CrossRef
  • 6,243 View
  • 40 Download
  • 1 Web of Science
  • Crossref

Correspondence

Viral hepatitis

Steatotic liver disease in chronic hepatitis C related hepatocellular carcinoma: Inflictor or bystander?: Correspondence to editorial on “Dynamic change of metabolic dysfunction-associated steatotic liver disease in chronic hepatitis C patients after viral eradication: A nationwide registry study in Taiwan”
Chung-Feng Huang, Ming-Lun Yeh, Chia-Yen Dai, Jee-Fu Huang, Wan-Long Chuang, Ming-Lung Yu
Clin Mol Hepatol 2025;31(1):e64-e66.
Published online August 19, 2024
DOI: https://doi.org/10.3350/cmh.2024.0638

Citations

Citations to this article as recorded by  Crossref logo
  • 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
  • Hepatitis C virus and cardiovascular disease: Current knowledge and unmet needs
    Chih-Wen Wang, Jee-Fu Huang, Ming-Lung Yu, Wan-Long Chuang
    Tzu Chi Medical Journal.2025; 37(4): 371.     CrossRef
  • Metabolic Dysfunction‐Associated Steatotic Liver Disease After Hepatitis C Virus Cure
    Chung‐Feng Huang, Jee‐Fu Huang, Ming‐Lung Yu, Wan‐Long Chuang
    The Kaohsiung Journal of Medical Sciences.2025;[Epub]     CrossRef
  • 5,435 View
  • 63 Download
  • 3 Web of Science
  • Crossref

Original Article

Steatotic liver disease

Dynamic change of metabolic dysfunction-associated steatotic liver disease in chronic hepatitis C patients after viral eradication: A nationwide registry study in Taiwan
Chung-Feng Huang, Chia-Yen Dai, Yi-Hung Lin, Chih-Wen Wang, Tyng-Yuan Jang, Po-Cheng Liang, Tzu-Chun Lin, Pei-Chien Tsai, Yu-Ju Wei, Ming-Lun Yeh, Ming-Yen Hsieh, Chao-Kuan Huang, Jee-Fu Huang, Wan-Long Chuang, Ming-Lung Yu
Clin Mol Hepatol 2024;30(4):883-894.
Published online July 29, 2024
DOI: https://doi.org/10.3350/cmh.2024.0414
Background/Aims
Steatotic liver disease (SLD) is a common manifestation in chronic hepatitis C (CHC). Metabolic alterations in CHC are associated with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to elucidate whether hepatitis C virus (HCV) eradication mitigates MASLD occurrence or resolution.
Methods
We enrolled 5,840 CHC patients whose HCV was eradicated by direct-acting antivirals in a nationwide HCV registry. MASLD and the associated cardiometabolic risk factors (CMRFs) were evaluated at baseline and 6 months after HCV cure.
Result
s: There were 2,147 (36.8%) patients with SLD, and 1,986 (34.0%) of them met the MASLD criteria before treatment. After treatment, HbA1c (6.0% vs. 5.9%, P<0.001) and BMI (24.8 kg/m2 vs. 24.7 kg/m2, P<0.001) decreased, whereas HDL-C (49.1 mg/dL vs. 51.9 mg/dL, P<0.001) and triglycerides (102.8 mg/dL vs. 111.9 mg/dL, P<0.001) increased significantly. The proportion of patients with SLD was 37.5% after HCV eradication, which did not change significantly compared with the pretreatment status. The percentage of the patients who had post-treatment MASLD was 34.8%, which did not differ significantly from the pretreatment status (P=0.17). Body mass index (BMI) (odds ratio [OR] 0.89; 95% confidence intervals [CI] 0.85–0.92; P<0.001) was the only factor associated with MASLD resolution. In contrast, unfavorable CMRFs, including BMI (OR 1.10; 95% CI 1.06–1.14; P<0.001) and HbA1c (OR 1.19; 95% CI 1.04–1.35; P=0.01), were independently associated with MASLD development after HCV cure.
Conclusions
HCV eradication mitigates MASLD in CHC patients. CMRF surveillance is mandatory for CHC patients with metabolic alterations, which are altered after HCV eradication and predict the evolution of MASLD.

Citations

Citations to this article as recorded by  Crossref logo
  • Editorial: Beyond Viral Eradication—Cardiometabolic Risk and Cardiovascular Outcomes After SVR in Chronic Hepatitis C. Authors' Reply
    Pei‐Chien Tsai, Jee‐Fu Huang, Ming‐Lung Yu
    Alimentary Pharmacology & Therapeutics.2026;[Epub]     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
  • Reply to comment on “Posttreatment FIB-4 score change predicts hepatocellular carcinoma in chronic hepatitis C patients: Findings from the Taiwan hepatitis C registry program”
    Hung-Wei Wang, Cheng-Yuan Peng, Ming-Lung Yu
    Journal of the Formosan Medical Association.2025;[Epub]     CrossRef
  • 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
  • Bridging the Gap in Elimination of Hepatitis C Virus among People Who Use Drugs in South Korea
    Beom Kyung Kim
    Gut and Liver.2025; 19(5): 635.     CrossRef
  • Long-term effects of HCV eradication on lipid profiles associated with MASLD among people with HIV with advanced fibrosis or cirrhosis
    Ana Virseda-Berdices, Belen Requena, Juan Berenguer, Juan Gónzalez-García, Carolina Gonzalez-Riano, Cristina Díez, Victor Hontañón, Paula Muñoz-García, Amanda Fernández-Rodríguez, Coral Barbas, Salvador Resino, Rubén Martín-Escolano, María Ángeles Jiménez
    Journal of Infection and Public Health.2025; 18(12): 102981.     CrossRef
  • Metabolic Dysfunction‐Associated Steatotic Liver Disease After Hepatitis C Virus Cure
    Chung‐Feng Huang, Jee‐Fu Huang, Ming‐Lung Yu, Wan‐Long Chuang
    The Kaohsiung Journal of Medical Sciences.2025;[Epub]     CrossRef
  • Advanced Fibrosis and Cardiometabolic Risk Burden Increase Major Cardiovascular Events in Chronic Hepatitis C Patients With Steatotic Liver Disease After Viral Eradication
    Pei‐Chien Tsai, Chung‐Feng Huang, Ming‐Lun Yeh, Yu‐Ju Wei, Chih‐Wen Wang, Tyng‐Yuan Jang, Po‐Cheng Liang, Yi‐Hung Lin, Chia‐Yen Dai, Jee‐Fu Huang, Wan‐Long Chuang, Ming‐Lung Yu
    Alimentary Pharmacology & Therapeutics.2025;[Epub]     CrossRef
  • Steatotic liver disease in patients with chronic hepatitis C
    Jakub Janczura, Michał Brzdęk, Robert Flisiak, Krystyna Dobrowolska, Kinga Brzdęk, Piotr Rzymski, Dorota Zarębska-Michaluk
    World Journal of Hepatology.2025;[Epub]     CrossRef
  • 6,004 View
  • 162 Download
  • 13 Web of Science
  • Crossref

Correspondence

Hepatic neoplasm

Perspective of the risk and molecular mechanisms of hepatocellular carcinoma after HCV eradication in the post-DAA era: Correspondence to editorial on “Unmet needs in the post-direct-acting antivirals era: The risk and molecular mechanisms of hepatocellular carcinoma after hepatitis C virus eradication”
Chung-Feng Huang, Manar Hijaze Awad, Meital Gal-Tanamy, Ming-Lung Yu
Clin Mol Hepatol 2024;30(4):1023-1025.
Published online July 1, 2024
DOI: https://doi.org/10.3350/cmh.2024.0472

Citations

Citations to this article as recorded by  Crossref logo
  • Long-Term Hepatic and Extrahepatic Outcomes of Chronic Hepatitis C Patients After Sofosbuvir-Based Treatment (LONGHEAD Study)
    Chung-Feng Huang, Jeong Heo, Rong-Nan Chien, Yang-Hyun Baek, Jia-Horng Kao, Ju-Hyun Kim, Ting-Tsung Chang, Kwan-Soo Byun, Jyh-Jou Chen, Sook-Hyang Jeong, Tsung-Hui Hu, Young-Seok Kim, Cheng-Yuan Peng, Won-Young Tak, Horng-Yuan Wang, Seung-Kew Yoon, I.-Shy
    Infectious Diseases and Therapy.2025; 14(5): 1089.     CrossRef
  • Genomic biomarkers to predict response to atezolizumab plus bevacizumab immunotherapy in hepatocellular carcinoma: Insights from the IMbrave150 trial
    Sun Young Yim, Sung Hwan Lee, Seung-Woo Baek, Bohwa Sohn, Yun Seong Jeong, Sang-Hee Kang, Kena Park, Hyewon Park, Sunyoung S. Lee, Ahmed O. Kaseb, Young Nyun Park, Sun-Hee Leem, Michael A. Curran, Ji Hoon Kim, Ju-Seog Lee
    Clinical and Molecular Hepatology.2024; 30(4): 807.     CrossRef
  • Reply to correspondence on “Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy”
    Seren M. Gedallovich, Paul Y. Kwo
    Clinical and Molecular Hepatology.2024; 30(4): 1050.     CrossRef
  • 5,044 View
  • 64 Download
  • 1 Web of Science
  • Crossref

Review

Viral hepatitis

Unmet needs in the post-direct-acting antivirals era: The risk and molecular mechanisms of hepatocellular carcinoma after hepatitis C virus eradication
Chung-Feng Huang, Manar Hijaze Awad, Meital Gal-Tanamy, Ming-Lung Yu
Clin Mol Hepatol 2024;30(3):326-344.
Published online April 26, 2024
DOI: https://doi.org/10.3350/cmh.2024.0155
Hepatitis C virus (HCV) infection is one of the major etiologies of hepatocellular carcinoma (HCC) with approximately 30% of HCC being due to HCV infection worldwide. HCV eradication by antivirals greatly reduces the risk of HCC; nevertheless, HCC remains to occur in chronic hepatitis C (CHC) patients who have achieved a sustained virological response (SVR). The proportion of post-SVR HCC among newly diagnosed HCC patients is increasing in the direct-acting antiviral (DAA) era and might be due to preexisting inflammatory and fibrotic liver backgrounds, immune dysregulation between host and virus interactions, as well as host epigenetic scars, genetic predispositions and alternations. By means of applying surrogate markers and adopting risk stratification, HCC surveillance should be consistently performed in high-risk populations. In this review, we discuss the possible molecular mechanism, risk factors, and HCC surveillance strategy for HCC development after HCV eradication in CHC patients.

Citations

Citations to this article as recorded by  Crossref logo
  • Revisiting unmet needs in clinical research on direct-acting antiviral therapy for HCC patients: Correspondence to letter to the editor on “Direct-acting antiviral therapy for patients with HCV-related hepatocellular carcinoma: A nationwide cohort study”
    Teng-Yu Lee, Pei-Chien Tsai, Shou-Wu Lee, Ming- Lung Yu
    Clinical and Molecular Hepatology.2026; 32(1): e99.     CrossRef
  • Hepatitis A to E in People with HIV: A Virus-Specific Review of Prevention and Treatment
    Kuan-Yin Lin, Yi-Chia Huang, Miao-Hui Huang, Tsung-Yu Tsai, Guan-Jhou Chen, Yu-Shan Huang, Sung-Hsi Huang, Hsin-Yun Sun, Chien-Ching Hung
    Infectious Diseases and Therapy.2026; 15(2): 391.     CrossRef
  • Artificial Intelligence Applications in the Diagnosis, Treatment, and Prognosis of Hepatocellular Carcinoma
    Ming-Ying Lu, Jacky Chung-Hao Wu, Henry Horng-Shing Lu, Mohammed Eslam, Ming-Lung Yu
    Gut and Liver.2026; 20(1): 5.     CrossRef
  • Editorial: Beyond Viral Eradication—Cardiometabolic Risk and Cardiovascular Outcomes After SVR in Chronic Hepatitis C. Authors' Reply
    Pei‐Chien Tsai, Jee‐Fu Huang, Ming‐Lung Yu
    Alimentary Pharmacology & Therapeutics.2026;[Epub]     CrossRef
  • 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
  • Integrative analysis of serum proteomics and transcriptomics in hepatitis C
    Jianqiong Wang, Andong Xia, Min Tang, Shengjun Yang, Yandi Shen, Jinhua Dao, Rui Tao, Wei Yue
    Virology Journal.2025;[Epub]     CrossRef
  • High prevalence of antinuclear antibodies in hepatitis C related hepatocellular carcinoma
    Mohamed El-Far, Ahmed S. Mustafa, AbdelfattahM. Attallah, Mohamed A. Abdelrazek
    Journal of Immunoassay and Immunochemistry.2025; 46(3): 218.     CrossRef
  • LI-RADS for Diagnosing Hepatocellular Carcinoma in Patients with Noncirrhotic Chronic Hepatitis C
    Jihyun An, Rohee Park, Euichang Kim, Seong Kyun Na, Ha Il Kim, In-Hye Song, Young Seo Cho, Ji Hun Kang, Han Chu Lee, Seungbong Han, Jean-Charles Nault, Sang Hyun Choi, Ju Hyun Shim
    Radiology.2025;[Epub]     CrossRef
  • Long-Term Hepatic and Extrahepatic Outcomes of Chronic Hepatitis C Patients After Sofosbuvir-Based Treatment (LONGHEAD Study)
    Chung-Feng Huang, Jeong Heo, Rong-Nan Chien, Yang-Hyun Baek, Jia-Horng Kao, Ju-Hyun Kim, Ting-Tsung Chang, Kwan-Soo Byun, Jyh-Jou Chen, Sook-Hyang Jeong, Tsung-Hui Hu, Young-Seok Kim, Cheng-Yuan Peng, Won-Young Tak, Horng-Yuan Wang, Seung-Kew Yoon, I.-Shy
    Infectious Diseases and Therapy.2025; 14(5): 1089.     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
  • Racial Diversity in the Decline in Hepatocellular Carcinoma and Increasing Age at Diagnosis in a Primarily African American Medical Center Population
    Gabriel Boudagh, Ahmad Alnasart, Kenan Abou Chaer, Paul Naylor, Milton Mutchnick
    Onco.2025; 5(3): 30.     CrossRef
  • Direct-acting Antivirals Therapy for Hepatocellular Carcinoma in Hepatitis C Patients
    Seul Ki Han, Soon Koo Baik, Moon Young Kim
    Journal of Digestive Cancer Research.2025; 13(2): 150.     CrossRef
  • Meeting the challenges of hepatocellular carcinoma post sustained virologic response in the post-direct- acting antiviral era: A path forward: Editorial on “Unmet needs in the post-direct-acting antivirals era: The risk and molecular mechanisms of hepatoc
    Seren M. Gedallovich, Paul Y. Kwo
    Clinical and Molecular Hepatology.2024; 30(4): 677.     CrossRef
  • The role of artificial intelligence in the management of liver diseases
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    The Kaohsiung Journal of Medical Sciences.2024; 40(11): 962.     CrossRef
  • 8,478 View
  • 189 Download
  • 12 Web of Science
  • Crossref

Original Article

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.
Result
s: 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.

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Reply to Correspondence

Viral hepatitis

Reply to correspondence on “Cardiovascular risk in chronic hepatitis B patients treated with tenofovir disoproxil fumarate or tenofovir alafenamide”
Pin-Nan Cheng, Ming-Lung Yu
Clin Mol Hepatol 2024;30(4):1031-1032.
Published online April 11, 2024
DOI: https://doi.org/10.3350/cmh.2024.0228
  • 5,256 View
  • 64 Download

Correspondence

Viral hepatitis

Correspondence on Letter regarding “Toward hepatitis C virus elimination using artificial intelligence”
Ming-Ying Lu, Ming-Lung Yu
Clin Mol Hepatol 2024;30(2):274-275.
Published online March 5, 2024
DOI: https://doi.org/10.3350/cmh.2024.0152

Citations

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  • Prevalence and Modes of Transmission of Hepatitis C Virus Infection: A Historical Worldwide Review
    Tommaso Stroffolini, Giacomo Stroffolini
    Viruses.2024; 16(7): 1115.     CrossRef
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    Ming‐Ying Lu, Wan‐Long Chuang, Ming‐Lung Yu
    The Kaohsiung Journal of Medical Sciences.2024; 40(11): 962.     CrossRef
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Editorial

Viral hepatitis

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
Clin Mol Hepatol 2024;30(2):144-146.
Published online February 19, 2024
DOI: https://doi.org/10.3350/cmh.2024.0115

Citations

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  • Effect of switching from prior Nucleos(t)ide Analogue(s) to Tenofovir alafenamide on lipid profile and cardiovascular risk in patients with Chronic Hepatitis B
    Witchayaporn Praguylertluck, Apichat Kaewdech, Naichaya Chamroonkul, Teerha Piratvisuth, Pimsiri Sripongpun, Tyng-Yuan Jang
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    Hyeyeon Hong, Jonggi Choi
    Clinical and Molecular Hepatology.2024; 30(2): 272.     CrossRef
  • Reply to correspondence on “Cardiovascular risk in chronic hepatitis B patients treated with tenofovir disoproxil fumarate or tenofovir alafenamide”
    Pin-Nan Cheng, Ming-Lung Yu
    Clinical and Molecular Hepatology.2024; 30(4): 1031.     CrossRef
  • 6,855 View
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Original Article

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.
Result
s: 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.

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Review

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.

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Editorial

Steatotic liver disease

From nonalcoholic steatohepatitis, metabolic dysfunction-associated fatty liver disease, to steatotic liver disease: Updates of nomenclature and impact on clinical trials
Ming-Lun Yeh, Ming-Lung Yu
Clin Mol Hepatol 2023;29(4):969-972.
Published online September 18, 2023
DOI: https://doi.org/10.3350/cmh.2023.0359

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Review

Hepatic neoplasm

Utility of combining PIVKA-II and AFP in the surveillance and monitoring of hepatocellular carcinoma in the Asia-Pacific region
Do Young Kim, Bao Nguyen Toan, Chee-Kiat Tan, Irsan Hasan, Lyana Setiawan, Ming-Lung Yu, Namiki Izumi, Nguyen Nguyen Huyen, Pierce Kah-Hoe Chow, Rosmawati Mohamed, Stephen Lam Chan, Tawesak Tanwandee, Teng-Yu Lee, Thi Thanh Nguyen Hai, Tian Yang, Woo-Chang Lee, Henry Lik Yuen Chan
Clin Mol Hepatol 2023;29(2):277-292.
Published online January 30, 2023
DOI: https://doi.org/10.3350/cmh.2022.0212
Even though the combined use of ultrasound (US) and alpha-fetoprotein (AFP) is recommended for the surveillance of hepatocellular carcinoma (HCC), the utilization of AFP has its challenges, including accuracy dependent on its cut-off levels, degree of liver necroinflammation, and etiology of liver disease. Though various studies have demonstrated the utility of protein induced by vitamin K absence II (PIVKA-II) in surveillance, treatment monitoring, and predicting recurrence, it is still not recommended as a routine biomarker test. A panel of 17 experts from Asia-Pacific, gathered to discuss and reach a consensus on the clinical usefulness and value of PIVKA-II for the surveillance and treatment monitoring of HCC, based on six predetermined statements. The experts agreed that PIVKA-II was valuable in the detection of HCC in AFP-negative patients, and could potentially benefit detection of early HCC in combination with AFP. PIVKA-II is clinically useful for monitoring curative and intra-arterial locoregional treatments, outcomes, and recurrence, and could potentially predict microvascular invasion risk and facilitate patient selection for liver transplant. However, combining PIVKA-II with US and AFP for HCC surveillance, including small HCC, still requires more evidence, whilst its role in detecting AFP-negative HCC will potentially increase as more patients are treated for hepatitis-related HCC. PIVKA-II in combination with AFP and US has a clinical role in the Asia-Pacific region for surveillance. However, implementation of PIVKA-II in the region will have some challenges, such as requiring standardization of cut-off values, its cost-effectiveness and improving awareness among healthcare providers.

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  • 19,142 View
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Original Articles

Significant down-regulation of growth hormone receptor expression revealed as a new unfavorable prognostic factor in hepatitis C virus-related hepatocellular carcinoma
Ching-Chih Lin, Ta-Wei Liu, Ming-Lun Yeh, Yi-Shan Tsai, Pei-Chien Tsai, Chung-Feng Huang, Jee-Fu Huang, Wan-Long Chuang, Chia-Yen Dai, Ming-Lung Yu
Clin Mol Hepatol 2021;27(2):313-328.
Published online December 14, 2020
DOI: https://doi.org/10.3350/cmh.2020.0247
Background/Aims
Growth hormone (GH) is the main regulator of somatic growth, metabolism, and gender dimorphism in the liver. GH receptor (GHR) signaling in cancer is derived from a large body of evidence, although the GHR signaling pathway involved in the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC, remains unclear. We aimed to explore the expression of GHR and analyze its association with clinicopathologic features and prognosis of patients with chronic hepatitis C and HCC.
Methods
The expression of GHR mRNA was investigated by quantitative real-time polymerase chain reaction in paired tumors and adjacent non-tumorous (ANT) liver tissues of 200 patients with chronic hepatitis C and HCC. Western blotting and immunofluorescence assays using the HCV-infected Huh7.5.1 cell model was performed.
Result
s: GHR mRNA was significantly lower in HCV-HCC tissues than in corresponding ANT liver tissues. GHR mRNA and protein levels also decreased in the HCV-infected Huh7.5.1 cell model. Notably, lower GHR expression was associated with age of >60 years (P=0.0111) and worse clinicopathologic characteristics, including alpha-fetoprotein >100 ng/mL (P=0.0403), cirrhosis (P=0.0075), vascular invasion (P=0.0052), pathological stage II–IV (P=0.0002), and albumin ≤4.0 g/dL (P=0.0055), which were linked with poor prognosis of HCC. Most importantly, the high incidence of recurrence and poor survival rates in patients with a low ratio of tumor/ANT GHR (≤0.1) were observed, indicating that low expression levels of GHR had great risk for development of HCC in patients with chronic hepatitis C.
Conclusions
Our study demonstrates a significant down-regulation of GHR expression as a new unfavorable independent prognostic factor in patients with chronic hepatitis C and HCC.

Citations

Citations to this article as recorded by  Crossref logo
  • Integrated Multi-Omics Analysis Reveals Cytokine Network Dynamics and Prognostic Signatures in Hepatitis B Virus-Associated Hepatocellular Carcinoma
    Mo-Han Liu, Fu-Yong Zhang, Yuan-Jun Huang, Zhi-Hua Jiang, Qin-Yan Chen, Lu-Juan Zhang, Li-Ping Hu, Zhong-Liao Fang
    Applied Biochemistry and Biotechnology.2026;[Epub]     CrossRef
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    Reetobrata Basu, Cesar L Boguszewski, John J Kopchick
    Endocrine Reviews.2025; 46(2): 224.     CrossRef
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    Huanhou Su, Xuewen Zhou, Guanchuan Lin, Chaochao Luo, Wei Meng, Cui Lv, Yuting Chen, Zebin Wen, Xu Li, Yongzhang Wu, Changtai Xiao, Jian Yang, Jiameng Lu, Xingguang Luo, Yan Chen, Paul KH Tam, Chuanjiang Li, Haitao Sun, Xinghua Pan
    Advanced Science.2025;[Epub]     CrossRef
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    Lintao Xia, Xiuli Yan, Hui Zhang
    Pathology - Research and Practice.2025; 275: 156192.     CrossRef
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    Jialin Qu, Fenghao Sun, Yichen Hou, Haoran Qi, Xiaorong Sun, Ligang Xing
    BMC Cancer.2023;[Epub]     CrossRef
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    Yue Wang, Minah Kim, Chantal Buckley, Heather D. Maynard, Ries J. Langley, Jo K. Perry
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    Baozhu Zhang, Boyang Chang, Lu Wang, Yuzhong Xu
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    Yuanyuan Guo, Jing Yang, Hua Gao, Xin Tian, Xiaojian Zhang, Quancheng Kan
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  • Down-regulation of hepatic expression of GHR/STAT5/IGF-1 signaling pathway fosters development and aggressiveness of HCV-related hepatocellular carcinoma: Crosstalk with Snail-1 and type 2 transforming growth factor-beta receptor
    Mona A. Abu El-Makarem, Mariana F. Kamel, Ahmed A. Mohamed, Hisham A. Ali, Mahmoud R. Mohamed, Alaa El-Deen M. Mohamed, Ahmed M. El-Said, Mahmoud G. Ameen, Alshymaa A. Hassnine, Hatem A. Hassan, Gianfranco D. Alpini
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  • MustSeq, an alternative approach for multiplexible strand-specific 3’ end sequencing of mRNA transcriptome confers high efficiency and practicality
    Liyao Mai, Yinbin Qiu, Zhiwei Lian, Caiming Chen, Linlin Wang, Yao Yin, Siqi Wang, Xiang Yang, Yazi Li, Wanwan Peng, Chaochao Luo, Xinghua Pan
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  • 14,897 View
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Viral hepatitis

Comedications and potential drug-drug interactions with direct-acting antivirals in hepatitis C patients on hemodialysis
Po-Yao Hsu, Yu-Ju Wei, Jia-Jung Lee, Sheng-Wen Niu, Jiun-Chi Huang, Cheng-Ting Hsu, Tyng-Yuan Jang, Ming-Lun Yeh, Ching-I Huang, Po-Cheng Liang, Yi-Hung Lin, Ming-Yen Hsieh, Meng-Hsuan Hsieh, Szu-Chia Chen, Chia-Yen Dai, Zu-Yau Lin, Shinn-Cherng Chen, Jee-Fu Huang, Jer-Ming Chang, Shang-Jyh Hwang, Wan-Long Chuang, Chung-Feng Huang, Yi-Wen Chiu, Ming-Lung Yu
Clin Mol Hepatol 2021;27(1):186-196.
Published online December 3, 2020
DOI: https://doi.org/10.3350/cmh.2020.0180
Background/Aims
Direct‐acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population.
Methods
The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan.
Result
s: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10).
Conclusions
HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.

Citations

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Viral hepatitis

Scaling up the in-hospital hepatitis C virus care cascade in Taiwan
Chung-Feng Huang, Pey-Fang Wu, Ming-Lun Yeh, Ching-I Huang, Po-Cheng Liang, Cheng-Ting Hsu, Po-Yao Hsu, Hung-Yin Liu, Ying-Chou Huang, Zu-Yau Lin, Shinn-Cherng Chen, Jee-Fu Huang, Chia-Yen Dai, Wan-Long Chuang, Ming-Lung Yu
Clin Mol Hepatol 2021;27(1):136-143.
Published online December 3, 2020
DOI: https://doi.org/10.3350/cmh.2020.0150
Background/Aims
Obstacles exist in facilitating hepatitis C virus (HCV) care cascade. To increase timely and accurate diagnosis, disease awareness and accessibility, in-hospital HCV reflex testing followed by automatic appointments and a late call-back strategy (R.N.A. model) was applied. We aimed to compare the HCV treatment rate of patients treated with this strategy compared to those without.
Methods
One hundred and twenty-five anti-HCV seropositive patients who adopted the R.N.A. model in 2020 and another 1,396 controls treated in 2019 were enrolled to compare the gaps in accurate HCV RNA diagnosis to final treatment allocation.
Result
s: The HCV RNA testing rate was significantly higher in patients who received reflex testing than in those without reflex testing (100% vs. 84.8%, P<0.001). When patients were stratified according to the referring outpatient department, a significant improvement in the HCV RNA testing rate was particularly noted in patients from non-hepatology departments (100% vs. 23.3%, P<0.001). The treatment rate in HCV RNA seropositive patients was 83% (83/100) after the adoption of the R.N.A. model, among whom 96.1% and 73.9% of patients were from the hepatology and non-hepatology departments, respectively. Compared to subjects without R.N.A. model application, a significant improvement in the treatment rate was observed for patients from non-hepatology departments (73.9% vs. 27.8%, P=0.001). The application of the R.N.A. model significantly increased the in-hospital HCV treatment uptake from 6.4% to 73.9% for patients from non-hepatology departments (P<0.001).
Conclusions
The care cascade increased the treatment uptake and set up a model for enhancing in-hospital HCV elimination.

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Viral hepatitis

Use of glecaprevir/pibrentasvir in patients with chronic hepatitis C virus infection and severe renal impairment
Desmond Y. H. Yap, Kevin S. H. Liu, Yu-Chun Hsu, Grace L. H. Wong, Ming-Chang Tsai, Chien-Hung Chen, Ching-Sheng Hsu, Yee Tak Hui, Michael K. K. Li, Chen-Hua Liu, Yee-Man Kan, Ming-Lung Yu, Man-Fung Yuen
Clin Mol Hepatol 2020;26(4):554-561.
Published online August 28, 2020
DOI: https://doi.org/10.3350/cmh.2020.0058
Background/Aims
Data on treatment efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) for chronic hepatitis C virus (HCV) infection in Asian patients with severe renal impairment are limited. This study aimed to study the treatment and side effects of GLE/PIB in these patients infected with non-1 genotype (GT) HCV.
Methods
We prospectively recruited patients with Child’s A cirrhosis and eGFR <30 mL/min/1.73 m2 in Hong Kong and Taiwan during 2017–2018 to receive GLE/PIB treatment.
Result
s: Twenty-one patients (GT2, n=7; GT3, n=6; and GT6, n=8) received GLE/PIB for 11.2±1.8 weeks. All except one were treatment-naïve. GLE/PIB was initiated in 16 patients while on dialysis (seven on peritoneal dialysis [PD] and nine on hemodialysis) and in five patients before dialysis. One patient died of PD-related peritonitis during treatment and two were lost to follow up. The SVR12 rate in the remaining 18 patients was 100%. All patients achieved undetectable levels at 4-, 12-, 24- and 48-week after treatment. Patients with deranged alanine aminotransferase showed normalization after 4 weeks and the response was sustained for 48 weeks. No significant adverse event was observed.
Conclusions
GLE/PIB treatment was associated with high efficacy and tolerability in HCV-infected patients with severe renal impairment.

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    Reviews in Medical Virology.2025;[Epub]     CrossRef
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    Biomedicines.2024; 13(1): 55.     CrossRef
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    Frontiers in Public Health.2023;[Epub]     CrossRef
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    Akari Kaba, Shigeyoshi Yamanaga, Yuji Hidaka, Mariko Toyoda, Masayuki Kashima, Yoshi Takekuma, Akito Inadome, Hiroshi Yokomizo, Akira Miyata
    Transplantation Proceedings.2022; 54(2): 549.     CrossRef
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    Journal of the Formosan Medical Association.2022; 121(11): 2265.     CrossRef
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    Hepatology International.2022; 16(5): 1001.     CrossRef
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    Ji Eun Ryu, Myeong Jun Song, Seok-Hwan Kim, Jung Hyun Kwon, Sun Hong Yoo, Soon Woo Nam, Hee Chul Nam, Hee Yeon Kim, Chang Wook Kim, Hyun Yang, Si Hyun Bae, Do Seon Song, U Im Chang, Jin Mo Yang, Sung Won Lee, Hae Lim Lee, Soon Kyu Lee, Pil Soo Sung, Jeong
    The Korean Journal of Internal Medicine.2022; 37(5): 958.     CrossRef
  • Recent Information on Pan-Genotypic Direct-Acting Antiviral Agents for HCV in Chronic Kidney Disease
    Fabrizio Fabrizi, Federica Tripodi, Roberta Cerutti, Luca Nardelli, Carlo M. Alfieri, Maria F. Donato, Giuseppe Castellano
    Viruses.2022; 14(11): 2570.     CrossRef
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    Clinical and Molecular Hepatology.2021; 27(1): 81.     CrossRef
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    Paul Kwo, Deepti Dronamraju
    Clinical and Molecular Hepatology.2020; 26(4): 489.     CrossRef
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Reviews

Viral hepatitis

Unmet needs of chronic hepatitis C in the era of direct-acting antiviral therapy
Chung-Feng Huang, Ming-Lung Yu
Clin Mol Hepatol 2020;26(3):251-260.
Published online March 19, 2020
DOI: https://doi.org/10.3350/cmh.2020.0018
The treatment of chronic hepatitis C (CHC) has been revolutionized in an era of all-oral direct-acting antivirals (DAAs) since 2014. Satisfactory treatment efficacy and tolerability can be provided by novel DAAs. Nevertheless, there are still some unmet needs and emerging issues in the treatment of CHC in the DAA era. Certain hard-to-cure populations are prone to have inferior treatment responses, including patients with severe liver decompensation, active hepatocellular carcinoma (HCC), and hepatitis C virus (HCV) genotype 3 (HCV-3) infection and those who experience multiple DAA treatment failures. Hepatitis B virus (HBV) reactivation during and after DAA treatment has raised concern regarding the use of prophylactic antivirals against HBV throughout DAA treatment. However, the standard strategy for the use of prophylactic antivirals is not uniform across regional guidelines. In the post-sustained virological response (SVR) period, HCC still occurs in a substantial proportion of patients. Due to the relatively short follow-up period, the net benefit of the achievement of an SVR by DAAs in the reduction of extrahepatic manifestations has not yet been determined. Attention must also be paid to HCV reinfection, particularly in high-risk populations. The most critical and unmet need for HCV elimination is the large gap in the HCV care cascade at the population level. To accomplish the World Health Organization (WHO)’s goal for HCV elimination by 2030, the expansion of access to HCV care requires a continuous effort to overcome practical and political challenges.

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    The Kaohsiung Journal of Medical Sciences.2025;[Epub]     CrossRef
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Hepatic neoplasm

Direct-acting antivirals response in hepatocellular carcinoma: Does the presence of hepatocellular carcinoma matter?
Chung-Feng Huang, Ming-Lung Yu
Clin Mol Hepatol 2019;25(2):168-171.
Published online February 11, 2019
DOI: https://doi.org/10.3350/cmh.2018.1014
During the clinical trial development of directly acting antivirals (DAAs), evidence regarding the treatment efficacy in chronic hepatitis C patients with hepatocellular carcinoma (HCC) was scarce because these patients have always been excluded. Apart from the clinical trials, more HCC patients are currently being treated in daily practice, given that these treatments are highly effective and involve well-tolerated regimens. Large scale, real-world studies have demonstrated potentially suboptimal antiviral treatment efficacy in HCC patients who received DAAs. It is postulated that the impairment of the bioavailability of DAAs may account for the inferior treatment response. However, the results could not be generalized across all studies. The differing results were attributed to diverse patient characteristics, suboptimal regimens or imprecise definitions of active cancer statuses at the time of treatment initiation. Additional large-scale studies that utilize the treatment of choice in clearly defined HCC patients with different disease severities are warranted to clarify the issue.

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