{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:29:53Z","timestamp":1790022593933,"version":"4.0.1"},"reference-count":31,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Aim and Objectives: Direct-acting antiviral (DAA) therapy can cure chronic hepatitis C (CHC), and daclatasvir (DCV)\/asunaprevir (ASV) was the first interferon-free DAA therapy introduced in Korea. Patients who achieve sustained virologic response (SVR) after DAA treatment are expected to have good prognoses. Therefore, in this study, we aimed to investigate the prognosis of these patients. Materials and Methods: This multicenter prospective observational study included patients with CHC who achieved SVR after DCV\/ASV treatment. The primary endpoint was hepatocellular carcinoma (HCC) occurrence, which was reviewed annually. Results: We included 302 patients (median follow-up duration: 38 [16.5\u201360.0] months; median age: 58 [49\u201367] years) in the study. Cirrhosis was observed in 103 patients (34.1%), and the median Child\u2013Pugh score was 5.0. HCC occurred in 16 patients (5.3%) within six years post-SVR; these patients were older and had higher cirrhosis prevalence, alpha-fetoprotein levels, and fibrosis-4 index scores than did those without HCC development. Cox proportional hazards analysis revealed that age &gt; 71 years (p = 0.005) and cirrhosis (p = 0.035) were significant risk factors for HCC occurrence. Conclusions: Although the prognoses of patients who achieved SVR with DCV\/ASV therapy were generally good, the risk for HCC was present, especially in older patients and in those with cirrhosis. Hence, early treatment at younger ages and regular follow-up surveillance after achieving SVR are warranted.<\/jats:p>","DOI":"10.3390\/medicina59081436","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T12:26:39Z","timestamp":1691497599000},"page":"1436","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Prognosis of Patients with Chronic Hepatitis C Genotype 1b Infection Treated Using Daclatasvir\/Asunaprevir after Sustained Virologic Response: A 6-Year Multicenter Prospective Observational Study"],"prefix":"10.3390","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4993-2496","authenticated-orcid":false,"given":"Jae-Hyun","family":"Yoon","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, Chonnam National University Hospital, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6236-780X","authenticated-orcid":false,"given":"Sung-Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Hallym University, Anyang 14068, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Hyeon","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, Chonnam National University Hospital, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gi-Ae","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yewan","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5884-9993","authenticated-orcid":false,"given":"Ji-Won","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Hallym University, Anyang 14068, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong-Hee","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Inje University Sanggye Paik Hospital, Seoul 01757, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6396-0859","authenticated-orcid":false,"given":"Young-Sun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Korea University Medical Center, Seoul 08308, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8383-8524","authenticated-orcid":false,"given":"Jeong-Han","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, Konkuk University, Seoul 05030, Republic of Korea"},{"name":"Research Institute of Medical Science, School of Medicine, Konkuk University, Seoul 05030, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"ref_1","unstructured":"WHO (2021). Recommendations and Guidance on Hepatitis C Virus Self Testing, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S58","DOI":"10.1016\/j.jhep.2014.07.012","article-title":"Natural history of hepatitis C","volume":"61","author":"Westbrook","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"309","DOI":"10.3350\/cmh.2012.18.3.309","article-title":"Type and cause of liver disease in Korea: Single-center experience, 2005\u20132010","volume":"18","author":"Lee","year":"2012","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1002\/hep.24724","article-title":"Dual therapy with the nonstructural protein 5A inhibitor, daclatasvir, and the nonstructural protein 3 protease inhibitor, asunaprevir, in hepatitis C virus genotype 1b-infected null responders","volume":"55","author":"Chayama","year":"2012","journal-title":"Hepatology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.jhep.2012.11.012","article-title":"Characterization of virologic escape in hepatitis C virus genotype 1b patients treated with the direct-acting antivirals daclatasvir and asunaprevir","volume":"58","author":"Karino","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/jgh.13809","article-title":"Comparison of direct sequencing and Invader assay for Y93H mutation and response to interferon-free therapy in hepatitis C virus genotype 1b","volume":"33","author":"Hayashi","year":"2018","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.jhep.2013.07.043","article-title":"Is there sufficient evidence to recommend antiviral therapy in hepatitis C?","volume":"60","author":"Wedemeyer","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1053\/j.gastro.2018.10.033","article-title":"What are the benefits of a sustained virologic response to direct-acting antiviral therapy for hepatitis C virus infection?","volume":"156","author":"Ioannou","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S120","DOI":"10.1016\/j.jhep.2016.08.001","article-title":"Management of the patient with SVR","volume":"65","author":"Terrault","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.cgh.2009.10.026","article-title":"Antiviral therapy reduces risk of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis","volume":"8","author":"Singal","year":"2010","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1016\/j.cgh.2022.04.013","article-title":"Fibrosis Stage-specific Incidence of Hepatocellular Cancer After Hepatitis C Cure With Direct-acting Antivirals: A Systematic Review and Meta-analysis","volume":"21","author":"Kim","year":"2023","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1016\/j.cgh.2018.12.018","article-title":"Cost Effectiveness of Hepatocellular Carcinoma Surveillance after a Sustained Virologic Response to Therapy in Patients with Hepatitis C Virus Infection and Advanced Fibrosis","volume":"17","author":"Wong","year":"2019","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/jgh3.12749","article-title":"Real-world long-term analysis of daclatasvir plus asunaprevir in patients with hepatitis C virus infection","volume":"6","author":"Fujii","year":"2022","journal-title":"JGH Open"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1053\/j.gastro.2016.09.009","article-title":"Eradication of hepatitis C virus infection in patients with cirrhosis reduces risk of liver and non-liver complications","volume":"152","author":"Nahon","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1111\/hepr.13070","article-title":"Efficacy of daclatasvir plus asunaprevir in patients with hepatitis C virus infection undergoing and not undergoing hemodialysis","volume":"48","author":"Fujii","year":"2018","journal-title":"Hepatol. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3350\/kjhep.2012.18.1.1","article-title":"Revision and update on clinical practice guideline for liver cirrhosis","volume":"18","author":"Suk","year":"2012","journal-title":"Korean J. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1002\/hep.21178","article-title":"Development of a simple noninvasive index to predict significant fibrosis in patients with HIV\/HCV coinfection","volume":"43","author":"Sterling","year":"2006","journal-title":"Hepatology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1053\/jhep.2003.50346","article-title":"A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C","volume":"38","author":"Wai","year":"2003","journal-title":"Hepatology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"164","DOI":"10.3350\/cmh.2021.0193","article-title":"Cost-effectiveness of chronic hepatitis C screening and treatment","volume":"28","author":"Lee","year":"2022","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"794","DOI":"10.3904\/kjim.2017.368","article-title":"Daclatasvir and asunaprevir combination therapy for patients with chronic hepatitis C virus genotype 1b infection in real world","volume":"34","author":"Oh","year":"2019","journal-title":"Korean J. Intern. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1097\/MOG.0000000000000524","article-title":"Fibrosis reversal after hepatitis C virus elimination","volume":"35","author":"Rockey","year":"2019","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/jvh.13617","article-title":"Factors affecting long-term changes of liver stiffness in direct-acting anti-hepatitis C virus therapy: A multicentre prospective study","volume":"29","author":"Rosato","year":"2022","journal-title":"J. Viral Hepat."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.jhep.2021.09.013","article-title":"Incidence of liver- and non-liver-related outcomes in patients with HCV-cirrhosis after SVR","volume":"76","author":"Degasperi","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_24","first-page":"641","article-title":"Factors associated with failure to achieve SVR in hepatitis C Genotype 3 patients within an integrated care delivery system","volume":"21","author":"Cheetham","year":"2015","journal-title":"J. Manag. Care Spec. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"551500","DOI":"10.3389\/fphar.2020.551500","article-title":"Predicting Treatment Failure for Initiators of hepatitis C virus Treatment in the era of Direct-Acting antiviral Therapy","volume":"11","author":"Nabulsi","year":"2020","journal-title":"Front Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"EASL (2018). EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J. Hepatol., 69, 182\u2013236.","DOI":"10.1016\/j.jhep.2018.03.019"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1002\/hep.29913","article-title":"Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases","volume":"68","author":"Marrero","year":"2018","journal-title":"Hepatology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s12072-019-09988-7","article-title":"APASL HCV guidelines of virus-eradicated patients by DAA on how to monitor HCC occurrence and HBV reactivation","volume":"13","author":"Kanda","year":"2019","journal-title":"Hepatol. Int."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea (2022). 2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. Clin. Mol. Hepatol., 28, 583\u2013705.","DOI":"10.3350\/cmh.2022.0294"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1002\/hep.31060","article-title":"Hepatitis C guidance 2019 update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America recommendations for testing, managing, and treating hepatitis C virus infection","volume":"71","author":"Ghany","year":"2020","journal-title":"Hepatology"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"EASL (2020). EASL recommendations on treatment of hepatitis C: Final update of the series (\u2606). J Hepatol., 73, 1170\u20131218.","DOI":"10.1016\/j.jhep.2020.08.018"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/8\/1436\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:28:06Z","timestamp":1760128086000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/8\/1436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,8]]},"references-count":31,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["medicina59081436"],"URL":"https:\/\/doi.org\/10.3390\/medicina59081436","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,8]]}}}