{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T10:48:41Z","timestamp":1761562121703},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,7,6]],"date-time":"2016-07-06T00:00:00Z","timestamp":1467763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"The Research Program on Hepatitis and on HIV\/AIDS research from the Japan Agency for Medical Research and Development, AMED"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:sec><jats:label \/><jats:p>Sustained virological responses (SVR) by daclatasvir (DCV) and asunaprevir (ASV) therapy for genotype 1b hepatitis C virus (HCV) infected patients has been significantly affected by pre\u2010existence of Y93\u2009H resistance\u2010associated variants (RAVs) in the non\u2010structural protein 5A (NS5A) region. The aim of this study was to elucidate the dominancy of naturally occurring RAVs in viral quasispecies on treatment outcomes in patients with HCV. In total, 138 patients were prospectively selected from 152 patients treated with DCV and ASV, where evaluation of treatment outcomes at 12 weeks post\u2010treatment was possible. Pre\u2010treatment RAVs in the non\u2010structural protein 3 and NS5A regions were detected by polymerase chain reaction (PCR)\u2010Invader assays, and the ratio of Y93H RAVs in viral quasispecies was measured by quantitative PCR\u2010Invader assay. Among 25 patients detected the Y93H RAV, the Y93H ratio was 1\u201325% in 5 patients, 26\u201375% in 7 patients, and \u226576% in 13 patients. Overall, SVR at 12 weeks after the completion of treatment (SVR12) was 91% (125\/138), and those with Y93H ratios of &lt;1%, 1\u201325%, 26\u201375%, and \u226576% were 99%, 100%, 71%, and 23%, respectively. Thus, the SVR12 decreased as the HCV Y93H ratio increased (<jats:italic>P\u2009<\/jats:italic>&lt;\u20090.0001). The dominancy of pre\u2010treatment RAVs of DCV and ASV affected its treatment outcomes, suggesting that evaluating the dominancy of HCV RAVs could be required for every other direct\u2010acting antiviral agent treatments. <jats:bold><jats:italic>J. Med. Virol. 89:99\u2013105, 2017<\/jats:italic><\/jats:bold>. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmv.24608","type":"journal-article","created":{"date-parts":[[2016,6,23]],"date-time":"2016-06-23T06:42:17Z","timestamp":1466664137000},"page":"99-105","source":"Crossref","is-referenced-by-count":15,"title":["Impact of resistance\u2010associated variant dominancy on treatment in patients with HCV genotype 1b receiving daclatasvir\/asunaprevir"],"prefix":"10.1002","volume":"89","author":[{"given":"Hiroki","family":"Ikeda","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Internal Medicine St. Marianna University School of Medicine Kawasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsunamasa","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Internal Medicine St. Marianna University School of Medicine 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