{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T17:47:25Z","timestamp":1760550445125,"version":"3.37.3"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,1,17]],"date-time":"2018-01-17T00:00:00Z","timestamp":1516147200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP15K09019"],"award-info":[{"award-number":["JP15K09019"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2018,5]]},"abstract":"Summary<\/jats:title>It is unclear whether multiple nonstructural (NS<\/jats:styled-content>) 5A resistance\u2010associated substitutions (RAS<\/jats:styled-content>s) correlate with the outcome of sofosbuvir (SOF<\/jats:styled-content>) and ledipasvir (LDV<\/jats:styled-content>) therapy. We investigated the effects of multiple NS<\/jats:styled-content>5A RAS<\/jats:styled-content>s in NS<\/jats:styled-content>5A inhibitor\u2010na\u00efve patients with chronic hepatitis C virus genotype\u00a01b infection treated with SOF<\/jats:styled-content>\/LDV<\/jats:styled-content>. In 313 patients treated with SOF<\/jats:styled-content>\/LDV<\/jats:styled-content>, we assessed the effects of multiple NS<\/jats:styled-content>5A RAS<\/jats:styled-content>s on the sustained virological response (SVR<\/jats:styled-content>). RAS<\/jats:styled-content>s at L28, R30, L31, Q54, P58, Q62, A92, and Y93 in the NS<\/jats:styled-content>5A region were examined by direct sequencing. The prevalence of RAS<\/jats:styled-content>s was as follows: 2.6% at L28, 8.7% at R30, 6.1% at L31, 48.7% at Q54, 9.9% at P58, 9.9% at Q62, 5.1% at A92, 13.8% at Y93, and 19.2% at L31 or Y93. A total of 133 patients had no RAS<\/jats:styled-content>s. SVR<\/jats:styled-content> was achieved in 98.7% of the patients. SVR<\/jats:styled-content> rates significantly differed between patients with and without the L31 or Y93 RAS<\/jats:styled-content> (93.0% [53\/57] vs 100% [250\/250], P<\/jats:italic>\u00a0=\u00a0.0011). In addition, among patients with the L31 or Y93 RAS<\/jats:styled-content>, 29.8%, 45.6% and 24.6% had one, two and three or more NS<\/jats:styled-content>5A RAS<\/jats:styled-content>s, respectively. The SVR<\/jats:styled-content> rate was significantly lower in patients with the L31 or Y93 RAS<\/jats:styled-content> with more than three NS<\/jats:styled-content>5A RAS<\/jats:styled-content>s compared to those with fewer than three NS<\/jats:styled-content>5A RAS<\/jats:styled-content>s (71.4% [10\/14] vs 100% [43\/43], P<\/jats:italic>\u00a0=\u00a0.0025). Although the prevalence of multiple NS<\/jats:styled-content>5A RAS<\/jats:styled-content>s at baseline was low in NS<\/jats:styled-content>5A inhibitor\u2010na\u00efve patients, the presence of multiple NS<\/jats:styled-content>5A RAS<\/jats:styled-content>s was associated with the effectiveness of SOF<\/jats:styled-content>\/LDV<\/jats:styled-content> therapy.<\/jats:p>","DOI":"10.1111\/jvh.12850","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T10:37:08Z","timestamp":1514111828000},"page":"535-542","source":"Crossref","is-referenced-by-count":14,"title":["The presence of multiple NS<\/scp>5A RAS<\/scp>s is associated with the outcome of sofosbuvir and ledipasvir therapy in NS<\/scp>5A inhibitor\u2010na\u00efve patients with chronic HCV<\/scp> genotype 1b infection in a real\u2010world cohort"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0763-6760","authenticated-orcid":false,"given":"R.","family":"Kozuka","sequence":"first","affiliation":[{"name":"Department of Hepatology Osaka City University Graduate School of Medicine Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Hai","sequence":"additional","affiliation":[{"name":"Department of Hepatology Osaka City University Graduate School of Medicine Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Motoyama","sequence":"additional","affiliation":[{"name":"Department of Hepatology Osaka City University Graduate School of Medicine Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Hagihara","sequence":"additional","affiliation":[{"name":"Department of Hepatology Osaka City University Graduate School of Medicine Osaka 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