{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T04:37:34Z","timestamp":1740112654022,"version":"3.37.3"},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,9,23]],"date-time":"2018-09-23T00:00:00Z","timestamp":1537660800000},"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":["Hepatology Research"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Treatment with all\u2010oral direct\u2010acting antiviral agents (DAAs) elbasvir\/grazoprevir (EBR\/GZR) is associated with high sustained virologic response (SVR). The aim of this study was to evaluate the safety and treatment efficacy of EBR\/GZR in hepatitis C virus (HCV)\u2010infected patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This retrospective cohort study included 147 consecutive patients with chronic HCV genotype 1b infection who were treated with EBR (50\u00a0mg) plus GZR (100\u00a0mg) once daily for 12\u00a0weeks. The rates of SVR at 12\u00a0weeks after the end of treatment (SVR12) were evaluated based on patient baseline characteristics. Treatment efficacy was analyzed according to background chronic kidney disease (CKD), and retreatment efficacy in patients who failed to respond to previous DAAs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The SVR12 was 94% (138 of 147 patients), based on intention\u2010to\u2010treat analysis. Rates of SVR12 were 97% (131 of 135) and 58% (7 of 12) in cases na\u00efve to DAA treatment and failure to respond to prior DAAs, respectively. The SVR12 rates in patients with CKD stage 4\u20135 was 100% (8 of 8). All patients (4 of 4 patients) with stage 4\u20135 and advanced fibrosis (Fibrosis\u20104 index \u22653.25) also achieved SVR12. Multivariate analysis that included the above variables identified pretreatment with other DAAs as an independent factor that was significantly and independently associated with non\u2010SVR12 (odds ratio, 97.5; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). Relapsers of first DAAs, excluding the combination of ledipasvir and sofosbuvir, achieved SVR12. Characteristic novel non\u2010structural protein 5A substitutions were not detected after failure of retreatment with EBR\/GZR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Treatment with EBR\/GZR was highly efficacious with acceptable safety, even in patients with CKD stage 4\u20135. Retreatment of relapsers to prior DAAs, excluding ledipasvir and sofosbuvir, achieved SVR12.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.13242","type":"journal-article","created":{"date-parts":[[2018,8,20]],"date-time":"2018-08-20T05:06:07Z","timestamp":1534741567000},"page":"256-263","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Efficacy and safety of elbasvir plus grazoprevir combination therapy in Japanese patients infected with hepatitis C virus genotype 1b"],"prefix":"10.1111","volume":"49","author":[{"given":"Yasue","family":"Takeuchi","sequence":"first","affiliation":[{"name":"Department of Hepatology, Toranomon Hospital Okinaka Memorial Institute for Medical Research  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norio","family":"Akuta","sequence":"additional","affiliation":[{"name":"Department of Hepatology, Toranomon Hospital 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 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 Okinaka Memorial Institute for Medical Research  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1189-4287","authenticated-orcid":false,"given":"Shunichiro","family":"Fujiyama","sequence":"additional","affiliation":[{"name":"Department of Hepatology, Toranomon Hospital Okinaka Memorial Institute for Medical Research  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6148-0042","authenticated-orcid":false,"given":"Yusuke","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Department of Hepatology, Toranomon Hospital 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 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 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 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 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 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 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 Okinaka Memorial Institute for Medical Research  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,9,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.07.027"},{"key":"e_1_2_6_3_1","unstructured":"American Association for the Study of Liver Diseases\/Infectious Diseases Society of America.HCV Guidance: Recommendations for Testing Managing and Treating Hepatitis C Virus. Available at:https:\/\/www.hcvguidelines.org\/. Accessed May 7 2018."},{"key":"e_1_2_6_4_1","unstructured":"Zepatier (elbasvir and grazoprevir) package insert.Whitehouse Station: Merck 2016."},{"key":"e_1_2_6_5_1","first-page":"1940","article-title":"Pharmacokinetics of co\u2010administered HCV protease inhibitor MK\u20105172 and NS5A inhibitor MK\u20108742 in volunteers with end\u2010stage renal disease on hemodialysis or severe renal impairment not on hemodialysis","volume":"60","author":"Yeh WW","year":"2014","journal-title":"Hepatology"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00349-9"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.11.012"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-017-1380-8"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.24617"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21178"},{"key":"e_1_2_6_11_1","doi-asserted-by":"crossref","first-page":"9524","DOI":"10.1073\/pnas.87.24.9524","article-title":"Molecular cloning of the human hepatitis C virus genome from Japanese patients with non\u2010A, non\u2010B hepatitis","volume":"87","author":"Kato N","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP2729"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.04.003"},{"key":"e_1_2_6_14_1","first-page":"486","article-title":"The importance of resistance to direct antiviral drugs in HCV infection in clinical practice","volume":"64","author":"Sarrazin C","year":"2016","journal-title":"Gastroenterology"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2008.12.034"},{"key":"e_1_2_6_16_1","first-page":"S1","article-title":"KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease","volume":"3","author":"National Kidney Foundation","year":"2013","journal-title":"Kidney Int"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-011-9284-9"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0100790"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.12.003"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-016-1162-8"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-016-1174-4"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-017-1396-0"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-018-1429-3"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.24767"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29836"}],"container-title":["Hepatology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhepr.13242","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hepr.13242","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hepr.13242","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hepr.13242","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T10:45:12Z","timestamp":1694429112000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hepr.13242"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,23]]},"references-count":24,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1111\/hepr.13242"],"URL":"https:\/\/doi.org\/10.1111\/hepr.13242","archive":["Portico"],"relation":{},"ISSN":["1386-6346","1872-034X"],"issn-type":[{"type":"print","value":"1386-6346"},{"type":"electronic","value":"1872-034X"}],"subject":[],"published":{"date-parts":[[2018,9,23]]},"assertion":[{"value":"2018-06-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}