{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:53:07Z","timestamp":1768438387424,"version":"3.49.0"},"reference-count":26,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T00:00:00Z","timestamp":1637107200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health and Welfare (Taiwan)","award":["MOHW107-NHCP-D-211-112001"],"award-info":[{"award-number":["MOHW107-NHCP-D-211-112001"]}]},{"name":"Ministry of Health and Welfare (Taiwan)","award":["MOHW109-NHCP-D-211-122001"],"award-info":[{"award-number":["MOHW109-NHCP-D-211-122001"]}]},{"name":"Ministry of Education (Taiwan)","award":["NTU-109L901401"],"award-info":[{"award-number":["NTU-109L901401"]}]},{"name":"Ministry of Science and Technology (Taiwan)","award":["MOST 109-2634-F-002-043"],"award-info":[{"award-number":["MOST 109-2634-F-002-043"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>About 4% of the population in Taiwan are seropositive for anti-HCV Ab and 70% with HCV RNA. To address this high chronic hepatitis C disease load, Taiwan National Health Insurance started reimbursing genotype-specific DAAs in 2017 and pangenotype DAAs in mid-2018. With a 97% SVR12 rate, there were still 2\u20133% of patients that failed to clear HCV. To understand the causes of DAA failure in Taiwan, we conducted a multi-center, clinical, and virologic study. A total of 147 DAA-failure patients were recruited, and we searched HCV NS3\/4A, NS5A and NS5B for known resistance-associated substitutions (RASs) by population sequencing, and conducted whole genome sequencing (WGS) for those without known RASs. A total of 107 patients received genotype-specific DAAs while 40 had pangenotype DAAs. Clinically, the important cause of failure is poor adherence. Virologically, common RASs in genotype-specific DAAs were NS5A-L31, NS5A-Y93, and NS5B-C316, while common RASs in pangenotype DAAs were NS5A-L31, NS5A-A\/Q\/R30, and NS5A-Y93. Additionally, new amino acid changes were found by WGS. Finally, we identified 12 cases with inconsistent baseline and post-treatment HCV genotypes, which is suggestive of re-infection rather than treatment failure. Our study described the drug resistance profile for DAA failure in Taiwan, showing differences from other countries.<\/jats:p>","DOI":"10.3390\/v13112294","type":"journal-article","created":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T21:32:07Z","timestamp":1637184727000},"page":"2294","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Drug Resistance Profile and Clinical Features for Hepatitis C Patients Experiencing DAA Failure in Taiwan"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0075-1280","authenticated-orcid":false,"given":"Chun-Ming","family":"Hong","sequence":"first","affiliation":[{"name":"Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10022, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"You-Yu","family":"Lin","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Jen","family":"Liu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan"},{"name":"Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10022, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya-Yun","family":"Lai","sequence":"additional","affiliation":[{"name":"Center of Precision Medicine, National Taiwan University, Taipei 10055, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiou-Hwei","family":"Yeh","sequence":"additional","affiliation":[{"name":"Center of Precision Medicine, National Taiwan University, Taipei 10055, Taiwan"},{"name":"Graduate Institute of Microbiology, National Taiwan University College of Medicine, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hung-Chih","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10022, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2442-7952","authenticated-orcid":false,"given":"Jia-Horng","family":"Kao","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan"},{"name":"Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10022, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shih-Jer","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10022, Taiwan"},{"name":"Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin 64000, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5241-5425","authenticated-orcid":false,"given":"Yi-Hsiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Institute of Clinical Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei 11230, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng-Shun","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5841-974X","authenticated-orcid":false,"given":"Hsing-Tao","family":"Kuo","sequence":"additional","affiliation":[{"name":"Chi Mei Medical Center, Department of Internal Medicine, Tainan 71004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pin-Nan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8145-1900","authenticated-orcid":false,"given":"Ming-Lung","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8316-3785","authenticated-orcid":false,"given":"Pei-Jer","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan"},{"name":"Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10022, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,17]]},"reference":[{"key":"ref_1","unstructured":"WHO (2021, September 10). World Health Assembly, 69. Draft Global Health Sector Strategies: Viral Hepatitis, 2016\u20132021: Report by the Secretariat. Available online: https:\/\/apps.who.int\/iris\/handle\/10665\/252690."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.vhri.2013.08.001","article-title":"Estimating the Incidence and Prevalence of Chronic Hepatitis C Infection in Taiwan Using Back Projection","volume":"3","author":"McEwan","year":"2014","journal-title":"Value Health Reg. Issues"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jfma.2015.06.012","article-title":"Hepatitis C virus infection in Taiwan: Past, present and future","volume":"115","author":"Kao","year":"2016","journal-title":"J. Formos Med. Assoc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/jmv.2001","article-title":"Changing prevalence of hepatitis C virus genotypes: Molecular epidemiology and clinical implications in the hepatitis C virus hyperendemic areas and a tertiary referral center in Taiwan","volume":"65","author":"Yu","year":"2001","journal-title":"J. Med. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1002\/hep.26744","article-title":"Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: Updated criteria and genotype assignment Web resource","volume":"59","author":"Smith","year":"2014","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e690","DOI":"10.1097\/MD.0000000000000690","article-title":"Huge gap between clinical efficacy and community effectiveness in the treatment of chronic hepatitis C: A nationwide survey in Taiwan","volume":"94","author":"Yu","year":"2015","journal-title":"Medicine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S1607-551X(10)70073-5","article-title":"Viral hepatitis infections in southern Taiwan: A multicenter community-based study","volume":"26","author":"Yang","year":"2010","journal-title":"Kaohsiung J. Med. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.jfma.2020.04.003","article-title":"2020 Taiwan consensus statement on the management of hepatitis C: Part (I) general population","volume":"119","author":"Yu","year":"2020","journal-title":"J. Formos Med. Assoc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1053\/j.gastro.2018.10.024","article-title":"Status of Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection and Remaining Challenges","volume":"156","author":"Baumert","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2902","DOI":"10.3748\/wjg.v20.i11.2902","article-title":"Hepatitis C virus NS5A inhibitors and drug resistance mutations","volume":"20","author":"Nakamoto","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1002\/hep.24594","article-title":"Genotypic and phenotypic analysis of variants resistant to hepatitis C virus nonstructural protein 5A replication complex inhibitor BMS-790052 in humans: In vitro and in vivo correlations","volume":"54","author":"Fridell","year":"2011","journal-title":"Hepatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"447","DOI":"10.3851\/IMP3025","article-title":"Naturally occurring HCV NS5A\/B inhibitor resistance-associated mutations to direct-acting antivirals","volume":"21","author":"Nguyen","year":"2016","journal-title":"Antivir. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.antiviral.2015.11.011","article-title":"Naturally occurring resistance mutations within the core and NS5B regions in hepatitis C genotypes, particularly genotype 5a, in South Africa","volume":"127","author":"Blackard","year":"2016","journal-title":"Antiviral Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e24965","DOI":"10.5812\/jjm.24965","article-title":"Analysis of Naturally Occurring Resistant Mutations to Hepatitis C Virus NS3 Protease Inhibitors: A Preliminary Study in South of Iran","volume":"8","author":"Afrasiabi","year":"2015","journal-title":"Jundishapur J. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1111\/hepr.12590","article-title":"Naturally occurring hepatitis C virus protease inhibitors resistance-associated mutations among chronic hepatitis C genotype 1b patients with or without HIV co-infection","volume":"46","author":"Cao","year":"2016","journal-title":"Hepatol. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1128\/JCM.03633-14","article-title":"Naturally Occurring Resistance-Associated Variants of Hepatitis C Virus Protease Inhibitors in Poor Responders to Pegylated Interferon-Ribavirin","volume":"53","author":"Larrat","year":"2015","journal-title":"J. Clin. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1007\/s12072-015-9624-2","article-title":"HCV NS5A resistance-associated variants in a group of real-world Japanese patients chronically infected with HCV genotype 1b","volume":"9","author":"Hirotsu","year":"2015","journal-title":"Hepatol. Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"E115","DOI":"10.1111\/hepr.12474","article-title":"Naturally occurring, resistance-associated hepatitis C virus NS5A variants are linked to IL28B genotype and are sensitive to interferon-based therapy","volume":"45","author":"Itakura","year":"2015","journal-title":"Hepatol Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/liv.14011","article-title":"Hepatitis C: Is eradication possible?","volume":"39","author":"Lombardi","year":"2019","journal-title":"Liver Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.jfma.2020.04.002","article-title":"2020 Taiwan consensus statement on the management of hepatitis C: Part (II) special populations","volume":"119","author":"Yu","year":"2020","journal-title":"J. Formos Med. Assoc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1111\/liv.14849","article-title":"Factors associated with treatment failure of direct-acting antivirals for chronic hepatitis C: A real-world nationwide hepatitis C virus registry programme in Taiwan","volume":"41","author":"Chen","year":"2021","journal-title":"Liver Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3228","DOI":"10.1007\/s10620-018-5247-5","article-title":"Lack of Patient Compliance in Real-World Practice Negatively Affects Sustained Viral Response Rates to Direct Acting Agent Therapy for Hepatitis C","volume":"63","author":"Marshall","year":"2018","journal-title":"Dig. Dis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"100138","DOI":"10.1016\/j.jhepr.2020.100138","article-title":"Features of resistance-associated substitutions after failure of multiple direct-acting antiviral regimens for hepatitis C","volume":"2","author":"Itakura","year":"2020","journal-title":"JHEP Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"104694","DOI":"10.1016\/j.antiviral.2019.104694","article-title":"Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure","volume":"174","author":"Chen","year":"2020","journal-title":"Antiviral Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3349","DOI":"10.1093\/jac\/dkaa304","article-title":"Prevalence of resistance-associated substitutions and retreatment of patients failing a glecaprevir\/pibrentasvir regimen","volume":"75","author":"Dietz","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1111\/jvh.12932","article-title":"Evolution and persistence of resistance-associated substitutions of hepatitis C virus after direct-acting antiviral treatment failures","volume":"25","author":"Jeong","year":"2018","journal-title":"J. Viral Hepat."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/11\/2294\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:31:29Z","timestamp":1760167889000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/11\/2294"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,17]]},"references-count":26,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["v13112294"],"URL":"https:\/\/doi.org\/10.3390\/v13112294","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,17]]}}}