{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T12:04:47Z","timestamp":1776513887065,"version":"3.51.2"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,10,16]],"date-time":"2019-10-16T00:00:00Z","timestamp":1571184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["17fk0210104h0001"],"award-info":[{"award-number":["17fk0210104h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ribavirin (RBV) induces nucleotide (nt) substitutions in hepatitis C virus (HCV) genome nonstructural (NS) regions. Although emergence of drug resistance\u2010associated variants is associated with direct\u2010acting antiviral treatment failure, the effect of RBV on genome substitutions in such patients is unknown. Genotype 1b HCV subgenomic replicon cells were treated with RBV for 120\u2009hours. Six patients with chronic genotype 1b with HCV\u2010infected patients who failed to respond to prior daclatasvir plus asunaprevir (DCV\/ASV) therapy were treated with 12 weeks of sofosbuvir and ledipasvir plus RBV after 4 weeks of RBV monotherapy. RBV\u2010induced genome mutations in the HCV NS region (nt3493\u20109301) in replicon cells and in patients during 4 weeks of RBV monotherapy were analyzed by deep sequencing. RBV\u2010associated G\u2010to\u2010A and C\u2010to\u2010U transitions increased in a dose\u2010dependent manner in HCV replicon cells after the RBV treatment. In patients with prior DCV\/ASV treatment failures, the median serum HCV RNA level was 6.25\u2009\u00b1\u20090.31\u2009log\u2009IU\/mL at the start of RBV therapy and decreased significantly to 5.95\u2009\u00b1\u20090.4\u2009log\u2009IU\/mL (<jats:italic>P<\/jats:italic>\u2009=\u2009.03) after 4 weeks of RBV monotherapy. Although predominant HCV genome substitutions rates were similar between nontreatment and RBV\u2010treatment periods (0.042 and 0.031 per base pair, respectively; <jats:italic>P<\/jats:italic>\u2009\u2009=\u2009.248), the frequencies of G\u2010to\u2010A and C\u2010to\u2010U transitions significantly increased after RBV monotherapy. These transitions were enriched, particularly within the HCV NS3 region in all patients. RBV treatment induces G\u2010to\u2010A and C\u2010to\u2010U transitions in the HCV genome even in chronic patients with hepatitis C with prior DCV\/ASV treatment failures.<\/jats:p>","DOI":"10.1002\/jmv.25602","type":"journal-article","created":{"date-parts":[[2019,10,4]],"date-time":"2019-10-04T09:34:45Z","timestamp":1570181685000},"page":"210-218","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Ribavirin induces hepatitis C virus genome mutations in chronic hepatitis patients who failed to respond to prior daclatasvir plus asunaprevir therapy"],"prefix":"10.1002","volume":"92","author":[{"given":"Yuhei","family":"Saito","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science Hiroshima University  Hiroshima Japan"},{"name":"Research Center for Hepatology and Gastroenterology Hiroshima University  Hiroshima 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