Direct-acting antiviral therapy for patients with hepatitis C virus-related hepatocellular carcinoma: A nationwide cohort study

Shou-Wu Lee^{1

2

3}, Sheng-Shun Yang^{1

3

4}, Pei-Chien Tsai⁵, Chung-Feng Huang⁵, Chi-Yi Chen⁶, Chao-Hung Hung⁷, Chien-Hung Chen⁷, Chi-Ming Tai^{8

9}, Pin-Nan Cheng¹⁰, Hsing-Tao Kuo¹¹, Kuo-Chih Tseng¹², Lein-Ray Mo¹³, Ching-Chu Lo¹⁴, Yi-Hsiang Huang^{15

16}, Han-Chieh Lin¹⁷, Pei-Lun Lee¹⁸, Ming-Jong Bair^{19

20}, Te-Sheng Chang^{21

22}, Chun-Yen Lin²³, Szu-Jen Wang²⁴, Tsai-Yuan Hsieh²⁵, Tzeng-Hue Yang²⁶, Cheng-Yuan Peng²⁷, Chi-Chieh Yang²⁸, Lee-Won Chong²⁹, Chien-Wei Huang³⁰, Chih-Wen Lin³¹, Cheng-Hsin Chu³², Ming-Chang Tsai^{2

33}, Jia-Horng Kao³⁴, Chun-Jen Liu³⁴, Wan-Long Chuang⁵, Teng-Yu Lee^{1

2}, Ming-Lung Yu^{5

35}; TACR investigators

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
² School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
³ Department of Post-Baccalaureate Medicine, College of Medicine, Chung Hsing University, Taichung, Taiwan.
⁴ Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
⁵ Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁶ Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan.
⁷ Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
⁸ Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
⁹ School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan.
¹⁰ Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
¹¹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan.
¹² Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi; School of Medicine, Tzu Chi University, Hualien, Taiwan.
¹³ Tainan Municipal Hospital, Tainan, Taiwan.
¹⁴ Division of Gastroenterology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan.
¹⁵ Institute of Clinical Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
¹⁶ Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan.
¹⁷ Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
¹⁸ Liouying Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan.
¹⁹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan.
²⁰ Mackay Medical College, New Taipei, Taiwan.
²¹ Division of Hepatogastroenterology, Department of Internal Medicine, ChiaYi Chang Gung Memorial Hospital, Chiayi, Taiwan.
²² College of Medicine, Chang Gung University, Taoyuan, Taiwan.
²³ Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan.
²⁴ Division of Gastroenterology, Department of Internal Medicine, Yuan's General Hospital, Kaohsiung, Taiwan.
²⁵ Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
²⁶ Lotung Pohai Hospital, Lo-Hsu Medical Foundation, Yilan, Taiwan.
²⁷ School of Medicine, China Medical University; Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
²⁸ Department of Gastroenterology, Division of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan.
²⁹ Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
³⁰ Division of Gastroenterology, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan.
³¹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, and School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan.
³² Division of Gastroenterology and Hepatology, Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan.
³³ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
³⁴ Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
³⁵ Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan.

PMID: 39905837
PMCID: PMC12260621
DOI: 10.3350/cmh.2024.1015

Direct-acting antiviral therapy for patients with hepatitis C virus-related hepatocellular carcinoma: A nationwide cohort study

Shou-Wu Lee et al. Clin Mol Hepatol. 2025 Jul.

. 2025 Jul;31(3):899-913.

doi: 10.3350/cmh.2024.1015. Epub 2025 Feb 5.

Authors

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
² School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
³ Department of Post-Baccalaureate Medicine, College of Medicine, Chung Hsing University, Taichung, Taiwan.
⁴ Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
⁵ Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁶ Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan.
⁷ Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
⁸ Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
⁹ School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan.
¹⁰ Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
¹¹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan.
¹² Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi; School of Medicine, Tzu Chi University, Hualien, Taiwan.
¹³ Tainan Municipal Hospital, Tainan, Taiwan.
¹⁴ Division of Gastroenterology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan.
¹⁵ Institute of Clinical Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
¹⁶ Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan.
¹⁷ Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
¹⁸ Liouying Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan.
¹⁹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan.
²⁰ Mackay Medical College, New Taipei, Taiwan.
²¹ Division of Hepatogastroenterology, Department of Internal Medicine, ChiaYi Chang Gung Memorial Hospital, Chiayi, Taiwan.
²² College of Medicine, Chang Gung University, Taoyuan, Taiwan.
²³ Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan.
²⁴ Division of Gastroenterology, Department of Internal Medicine, Yuan's General Hospital, Kaohsiung, Taiwan.
²⁵ Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
²⁶ Lotung Pohai Hospital, Lo-Hsu Medical Foundation, Yilan, Taiwan.
²⁷ School of Medicine, China Medical University; Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
²⁸ Department of Gastroenterology, Division of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan.
²⁹ Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
³⁰ Division of Gastroenterology, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan.
³¹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, and School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan.
³² Division of Gastroenterology and Hepatology, Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan.
³³ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
³⁴ Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
³⁵ Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan.

PMID: 39905837
PMCID: PMC12260621
DOI: 10.3350/cmh.2024.1015

Abstract

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.

Conclusion: High SVR rates among HCC patients underscore the importance of DAA therapy in enhancing OS, reaffirming its efficacy across various HCC stages.

Keywords: Antivirals; Chronic hepatitis C; Liver cancer; Survival; Sustained virological response.

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Conflict of interest statement

Conflicts of Interest

TY Lee: research support from Gilead, Merck and Roche diagnostics; consultant of BMS, Gilead, and Astra- Zeneca and speaker of Abbvie, BMS, Eisai, Gilead, Roche and AstraZeneca.

ML Yu: research support from Abbvie, Abbott Diagnostic, BMS, Gilead, Merck and Roche diagnostics; consultant of Abbvie, Abbott Diagnostic, BMS, Gilead, Roche and Roche diagnostics and speaker of Abbvie, BMS, Eisai, Gilead, Roche and Roche diagnostics. All other authors declare that they do not have any relevant conflict of interest.

Figures

**Figure 1.**
Flowchart of patient selection. BCLC, Barcelona Clinic Liver Cancer; DAA, direct-acting antiviral; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HIV, human immunodeficiency virus; N, numbers; SVR, sustained virological response.

**Figure 2.**
Kaplan–Meier analysis of overall survival in patients with or without SVR. All HRs (95% CIs) and P-values were calculated by the Cox subdistribution hazards method. *Adjusted for age, gender, diabetes mellitus, hypertension, cerebral vascular accident, coronary heart disease, chronic kidney disease, hepatocellular carcinoma, and liver cirrhosis. CI, confidence interval; HR, hazard ratio; N, numbers; OS, overall survival; SVR, sustained virological response.

**Figure 3.**
Kaplan–Meier analysis of overall survival in HCC patients with or without SVR. All HRs (95% CIs) and P-values were calculated by the Cox subdistribution hazards method. *Adjusted for gender, diabetes mellitus, chronic kidney disease, liver cirrhosis, and BCLC stage. BCLC, Barcelona Clinic Liver Cancer; CI, confidence interval; HCC, hepatocellular carcinoma; HR, hazard ratio; N, numbers; OS, overall survival; SVR, sustained virological response.

**Figure 4.**
Kaplan–Meier analysis of overall survival in HCC patients with or without SVR (BCLC stage 0-A or B-C). All HRs (95% CIs) and P-values were calculated by the Cox subdistribution hazards method. *Adjusted for gender, diabetes mellitus, chronic kidney disease, and liver cirrhosis. BCLC, Barcelona Clinic Liver Cancer; CI, confidence interval; HCC, hepatocellular carcinoma; HR, hazard ratio; N, numbers; OS, overall survival; SVR, sustained virological response.

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Direct-acting antiviral therapy for patients with hepatitis C virus-related hepatocellular carcinoma: A nationwide cohort study

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Direct-acting antiviral therapy for patients with hepatitis C virus-related hepatocellular carcinoma: A nationwide cohort study

Authors

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Conflict of interest statement

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