{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:20:41Z","timestamp":1760955641195},"reference-count":18,"publisher":"Wiley","issue":"2","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":"Ministry of Health, Labor and Welfare, Japan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:sec><jats:label \/><jats:p>Predictors of treatment efficacy with ledipasvir plus sofosbuvir as direct\u2010acting antiviral (DAA) regimen for HCV infection are still unclear. Retreatment efficacy of ledipasvir plus sofosbuvir for failures to prior DAA regimens, including NS5A inhibitors, are also unknown because resistance\u2010associated variants (RAVs) in NS5A have been shown to persist up to the long\u2010term of post\u2010treatment. One hundred seventy\u2010five patients with chronic HCV genotype 1 infection, without decompensated liver cirrhosis and hepatocellular carcinoma, were evaluated SVR12 by ledipasvir 90\u2009mg plus sofosbuvir 400\u2009mg once\u2010daily for 12 weeks. Overall, SVR12 were 92%, based on intention to treat analysis. In failures to daclatasvir plus asunaprevir, SVR12 were 71%. The study using ultra\u2010deep sequencing showed that ledipasvir plus sofosbuvir was effective to one case of failures to daclatasvir plus asunaprevir with multidrug RAVs (triple mutation in NS3\u2010D168\/NS5A\u2010L31\/NS5A\u2010Y93). Multivariate analysis identified FIB4 index (&lt;3.25), <jats:italic>IL28B<\/jats:italic> rs8099917 (TT type), and NS5A\u2010L31 (Wild type) as significant determinants of SVR12. SVR12 rates in patients with three factors of poor response (RAVs Positive, <jats:italic>IL28B<\/jats:italic> non\u2010TT, and FIB4 index \u22653.25) simultaneously were significantly lower than those of the other patients. Prediction of response to therapy based on combination of three predictors had high sensitivity and positive predictive values. In conclusions, this study indicated the favorable efficacy of ledipasvir plus sofosbuvir for HCV genotype 1 infection, including multidrug RAVs in Japan. Treatment efficacy could be predicted by the combination of viral and host factors. <jats:bold><jats:italic>J. Med. Virol. 89:284\u2013290, 2017<\/jats:italic>.<\/jats:bold> \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmv.24617","type":"journal-article","created":{"date-parts":[[2016,6,30]],"date-time":"2016-06-30T11:37:21Z","timestamp":1467286641000},"page":"284-290","source":"Crossref","is-referenced-by-count":46,"title":["Retreatment efficacy and predictors of ledipasvir plus sofosbuvir to HCV genotype 1 in Japan"],"prefix":"10.1002","volume":"89","author":[{"given":"Norio","family":"Akuta","sequence":"first","affiliation":[{"name":"Department of Hepatology Toranomon Hospital, and Okinaka Memorial Institute for Medical Research Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitomi","family":"Sezaki","sequence":"additional","affiliation":[{"name":"Department of Hepatology Toranomon Hospital, and Okinaka Memorial Institute for Medical Research Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumitaka","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Hepatology Toranomon Hospital, and Okinaka Memorial Institute for Medical Research Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunichiro","family":"Fujiyama","sequence":"additional","affiliation":[{"name":"Department of Hepatology Toranomon Hospital, and Okinaka Memorial Institute for Medical Research Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Department of Hepatology Toranomon Hospital, and Okinaka Memorial Institute for Medical Research Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Hosaka","sequence":"additional","affiliation":[{"name":"Department of Hepatology Toranomon Hospital, and Okinaka Memorial Institute for Medical Research Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Hepatology Toranomon Hospital, and Okinaka Memorial Institute for Medical Research Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariko","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Liver Research Laboratory Toranomon Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Saitoh","sequence":"additional","affiliation":[{"name":"Department of Hepatology Toranomon Hospital, and Okinaka Memorial Institute for Medical Research Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiyuki","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Hepatology Toranomon Hospital, and Okinaka Memorial Institute for Medical Research Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuji","family":"Arase","sequence":"additional","affiliation":[{"name":"Department of Hepatology Toranomon Hospital, and Okinaka Memorial Institute for Medical Research Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Hepatology Toranomon Hospital, and Okinaka Memorial Institute for Medical Research Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromitsu","family":"Kumada","sequence":"additional","affiliation":[{"name":"Department of Hepatology Toranomon Hospital, and Okinaka Memorial Institute for Medical Research Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,7,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402454"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1316366"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.23579"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/jlts.2003.50073"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-014-0052-8"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP3009"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.11.012"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402355"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27113"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)70099-X"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.03.030"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006370107"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28425"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21178"},{"key":"e_1_2_8_16_1","first-page":"837","article-title":"Aging of patients with hepatitis C virus\u2010associated hepatocellular carcinoma: Long\u2010term trends in Japan","volume":"16","author":"Taura N","year":"2006","journal-title":"Oncol Rep"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0112647"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00038-12"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000087257"}],"container-title":["Journal of Medical Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjmv.24617","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjmv.24617","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.24617","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T05:07:53Z","timestamp":1696568873000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmv.24617"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,6]]},"references-count":18,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,2]]}},"alternative-id":["10.1002\/jmv.24617"],"URL":"https:\/\/doi.org\/10.1002\/jmv.24617","archive":["Portico"],"relation":{},"ISSN":["0146-6615","1096-9071"],"issn-type":[{"value":"0146-6615","type":"print"},{"value":"1096-9071","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,6]]}}}