Clinical and Molecular Hepatology

"Sustained virological response"

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

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
Letter: Methodological Considerations in Interpreting Polygenic Risk Scores for Hepatocellular Carcinoma After SVR. Authors' Reply
Yu‐Sheng Lin, Yun‐Yu Chen, Teng‐Yu Lee
Alimentary Pharmacology & Therapeutics.2026; 63(10): 1439. CrossRef
Editorial: Residual HCC Risk After Hepatitis C Cure—Can Polygenic Risk Scores Refine Surveillance? Authors' Reply
Yu‐Sheng Lin, Hwai‐I Yang, Teng‐Yu Lee
Alimentary Pharmacology & Therapeutics.2026; 63(10): 1429. CrossRef
Letter: Beyond Association—Operationalising PRS‐5 for Hepatocellular Carcinoma Surveillance. Authors' Reply
Yu‐Sheng Lin, Ying‐Cheng Lin, Teng‐Yu Lee
Alimentary Pharmacology & Therapeutics.2026; 63(10): 1443. 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

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Editorials

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-analysis”: Ho Soo Chun, Minjong Lee; Clin Mol Hepatol 2025;31(1):261-263.
Published online September 20, 2024; DOI: https://doi.org/10.3350/cmh.2024.0795

Citations

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Understanding liver and digestive diseases: a paved road to improve diagnosis, management, and treatment
Ina Bergheim, Jean Francois Cadranel, Jianguo Chen, Wenxing Ding, Robert Eferl, Carmen Garcia-Ruiz, Hartmut Jaeschke, Firouzeh Kazerouni, Amedeo Lonardo, Derek A. Mann, Nahum Méndez-Sánchez, Camelia Mokhtari, Han Moshage, Chiara Raggi, Pavel Strnad, Oren
Exploration of Digestive Diseases.2026;[Epub] CrossRef

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Crossref

The effect of alanine aminotransferase dynamics on predicting sustained virological response in chronic hepatitis C virus infection: Tae Yeob Kim; Korean J Hepatol 2012;18(1):29-31.
Published online March 22, 2012; DOI: https://doi.org/10.3350/kjhep.2012.18.1.29

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Repeated Hepatitis C Virus Recurrence in a Patient With a Prognosis of Ultimate Spontaneous Clearance: Relapse or Reinfection?
Jinyong Wang, Di Dai, Ying Wen
American Journal of Therapeutics.2023; 30(5): e470. CrossRef
MDR1 gene C3435T polymorphism in chronic hepatitis C patients
Mehdi Parsa Nahad, Manoochehr Makvandi, Ali Teimoori, Shahram Jalilian, Gholam Abbas Kayedani, Sara Mahmoodi
Microbial Pathogenesis.2018; 114: 63. CrossRef
The Evaluation of Interferon Lambda 4 rs368234815 as a Predictor Factor in Treated Patients with Chronic Hepatitis C Genotype 1a Infection
Shahram Jalilian, Seyed Mahmoud Latifi, Manoochehr Makvandi, Ali Teimoori, Azarakhsh Azaran, Mehdi Parsanahad, Gholamabas Kayedani
Indian Journal of Medical Microbiology.2017; 35(2): 262. CrossRef
Peginterferon Alfa-2a Is Associated with Elevations in Alanine Aminotransferase at the End of Treatment in Chronic Hepatitis C Patients with Sustained Virologic Response
Chih-Wei Tseng, Chi-Yi Chen, Ting-Tsung Chang, Shinn-Jia Tzeng, Yu-Hsi Hsieh, Tsung-Hsing Hung, Ching-Chih Lee, Shu-Fen Wu, Kuo-Chih Tseng, Ming-Lung Yu
PLoS ONE.2014; 9(6): e100207. CrossRef

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Original Article

Durability of a sustained virological response in chronic hepatitis C patients treated with pegylated interferon alfa and ribavirin: Sang Bun Choi, Youn Jae Lee, Jae Ik Lee, Young Jin Song, Byoung Jin Choi, Jong Han Kim, Eun Uk Jung, Sung Jae Park, Sang Heon Lee, Ji Hyun Kim, Jung Sik Choi, Sam Ryong Jee, Sang Yong Seol; Korean J Hepatol 2011;17(3):183-188.
Published online September 30, 2011; DOI: https://doi.org/10.3350/kjhep.2011.17.3.183

Abstract
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Background/Aims

The reappearance rates of hepatitis C virus (HCV) RNA after a sustained virological response (SVR) have been reported to be 1-2%. We investigated the reappearance rate of HCV RNA after SVR in chronic hepatitis C (CHC) patients treated with pegylated interferon (PEG-IFN) and ribavirin.

Methods

In total, 292 CHC patients who achieved an SVR after PEG-IFN and ribavirin treatment were included. They were treated with subcutaneous injections of either PEG-IFN-α 2a or 2b plus ribavirin orally. Liver function tests and qualitative HCV RNA assays were performed every 6 months during the follow-up period after an SVR.

Results

Among the 292 patients, 224 (genotype 1, 92; genotype non-1, 132) were followed up for more than 6 months after SVR. These 224 patients were aged 48.1±11.5 years (mean±SD), and 129 of them were male. The median follow-up duration was 18 months (range 6-60 months). The reappearance rate of HCV RNA during follow-up was 0%. Two patients who achieved an SVR developed hepatocellular carcinoma during the follow-up period.

Conclusions

An SVR was maintained in all CHC patients treated with PEG-IFN plus ribavirin during a median follow-up of 18 months. However, a screening test for hepatocellular carcinoma is needed for patients with an SVR.

Citations

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Risk of Late Relapse or Reinfection With Hepatitis C Virus After Achieving a Sustained Virological Response: A Systematic Review and Meta-analysis
Bryony Simmons, Jawaad Saleem, Andrew Hill, Richard D. Riley, Graham S. Cooke
Clinical Infectious Diseases.2016; 62(6): 683. CrossRef
Long-term maintenance of sustained virological response in liver transplant recipients treated for recurrent hepatitis C
Francesca Romana Ponziani, Raffaella Viganò, Rosa Maria Iemmolo, Maria Francesca Donato, Maria Rendina, Pierluigi Toniutto, Luisa Pasulo, Maria Cristina Morelli, Patrizia Burra, Lucia Miglioresi, Manuela Merli, Daniele Di Paolo, Stefano Fagiuoli, Antonio
Digestive and Liver Disease.2014; 46(5): 440. CrossRef
Durability of antiviral therapy for chronic hepatitis C after achieving sustained virological response
Jeong Heo
The Korean Journal of Hepatology.2011; 17(3): 180. CrossRef

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Editorial

Durability of antiviral therapy for chronic hepatitis C after achieving sustained virological response: Jeong Heo; Korean J Hepatol 2011;17(3):180-182.
Published online September 30, 2011; DOI: https://doi.org/10.3350/kjhep.2011.17.3.180

8,961 View
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Original Article

Comparison of therapeutic results between combination therapy of peginterferon alpha-2a plus ribavirin and interferon alpha-2b plus ribavirin according to treatment duration in patients with chronic hepatitis C: Heon Ju Lee , Jong Ryul Eun , Jae Won Choi , Kyung Ok Kim , Hee Jung Moon; Korean J Hepatol 2008;14(1):46-57.
Published online March 20, 2008; DOI: https://doi.org/10.3350/kjhep.2008.14.1.46

Abstract
PDF

Background/Aims
This study compared the efficacy and safety of combined peginterferon alfa (PEG-IFN) and ribavirin with that of combined interferon alpha (IFN-α) and ribavirin, according to the treatment duration in Korean patients with chronic hepatitis C. Methods: Medical records of 86 patients treated with PEG-IFN and ribavirin (mean age, 50.7 years; males/females, 57/29; genotypes 1/2, 59/27) and 134 patients treated with IFN-α and ribavirin (mean age, 50.9 years; males/females 74/60; genotypes 1/2, 79/55) were reviewed. Ribavirin was administered at doses of 600-1,200 mg and 600-800 mg in patients with genotypes 1 and 2, respectively. Results: Sustained virological responses (SVRs) were evident in 68.4% and 41.7% of genotype 1 patients treated for 48 weeks in the PEG-IFN and IFN-α groups, respectively (P=0.021), and in 94.1% and 64.9% of genotype 2 patients treated for 24 weeks (P=0.026). Some genotype 1 patients treated for 24 weeks in the PEG-IFN group, who all exhibited negative HCV PCR results at week 12, showed an SVR of 87.5% (7/8). Conclusions: The rate of SVRs in Korean patients with chronic hepatitis C was higher for combined PEG-IFN and ribavirin than for combined IFN-α and ribavirin. Further study is needed to clarify the outcome of short-term therapy in patients with a rapid or early virological response. (Korean J Hepatol 2008;14:46- 57)

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