{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T09:04:16Z","timestamp":1772010256139,"version":"3.50.1"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:p>Genotype 4 hepatitis C virus (HCV) was considered difficult to treat in the era of pegylated interferon\u2010alpha (Peg\u2010IFN\u2010\u03b1) and ribavirin regimens. We evaluated the efficacy and safety of therapy with the nonstructural (NS) 5A inhibitor, ledipasvir, combined with the NS5B polymerase inhibitor, sofosbuvir, in patients with HCV genotype 4. In this phase 2, open\u2010label study, 44 patients (22 treatment na\u00efve and 22 treatment experienced) received a fixed\u2010dose combination tablet of 90 mg of ledipasvir and 400 mg of sofosbuvir orally once\u2010daily for 12 weeks. The primary endpoint was the percentage of patients with HCV RNA &lt;15 IU\/mL 12 weeks after stopping therapy (SVR12). Among study participants, HCV genotype 4 subtypes were well represented (4a, n = 25; 4d, n = 10; other subtypes, n = 9). Ten patients (23%) had compensated cirrhosis. Of the 22 treatment\u2010experienced patients, 21 (95%) had a non\u2010CC <jats:italic toggle=\"yes\">IL<\/jats:italic>\u2010<jats:italic toggle=\"yes\">28B<\/jats:italic> genotype. All 44 patients completed the full 12 weeks of dosing. The SVR12 rate was 93% (41 of 44; 95% confidence interval, 81\u201099). SVR12 rates were similar between treatment\u2010na\u00efve (95%; 21 of 22) and treatment\u2010experienced (91%; 20 of 22) patients. All 3 patients who did not achieve SVR12 had virological relapse within 4 weeks of the end of treatment; all 3 had baseline HCV RNA \u2265800,000 IU\/mL, a non\u2010CC <jats:italic toggle=\"yes\">IL\u201028B<\/jats:italic> genotype, and pretreatment NS5A resistance\u2010associated variants. None of the patients who relapsed had cirrhosis. The most common adverse events were asthenia, headache, and fatigue. No patients experienced a serious adverse event. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: The all\u2010oral regimen of ledipasvir and sofosbuvir is an effective and safe treatment for a wide range of HCV 4 subtypes in both treatment\u2010na\u00efve and \u2010experienced patients, including those with compensated cirrhosis. (EudraCT number: 2013\u2010003978\u201027; Clinicaltrials.gov NCT02081079) (H<jats:sc>epatology<\/jats:sc> 2016;64:1049\u20101056)<\/jats:p>","DOI":"10.1002\/hep.28706","type":"journal-article","created":{"date-parts":[[2016,6,28]],"date-time":"2016-06-28T23:07:01Z","timestamp":1467155221000},"page":"1049-1056","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":100,"title":["Ledipasvir plus sofosbuvir for 12 weeks in patients with hepatitis C genotype 4 infection"],"prefix":"10.1097","volume":"64","author":[{"given":"Armand","family":"Abergel","sequence":"first","affiliation":[{"name":"Department of Hepatology and Gastroenterology,Centre Hospitalier Universitaire Estaing,Universit\u00e9 d'Auvergne,UMR CNRS 6284,Clermont\u2010Ferrand,France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Metivier","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology,Centre Hospitalier Universitaire Purpan,Toulouse,France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Didier","family":"Samuel","sequence":"additional","affiliation":[{"name":"Centre H\u00e9pato\u2010Biliaire, H\u00f4pital Paul Brousse, Assistance Publique\u2010H\u00f4pitaux de Paris, UMR\u2010S 1193,Universit\u00e9 Paris\u2010Sud,INSERM U785,Villejuif,France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deyuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc,Foster City,CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn","family":"Kersey","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc,Foster City,CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillip S.","family":"Pang","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc,Foster City,CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evguenia","family":"Svarovskaia","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc,Foster City,CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven J.","family":"Knox","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc,Foster City,CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronique","family":"Loustaud\u2010Ratti","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology,Centre Hospitalier Universitaire Limoges, U850 INSERM,Universit\u00e9 de Limoges,Limoges,France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tarik","family":"Asselah","sequence":"additional","affiliation":[{"name":"Department of Hepatology, H\u00f4pital Beaujon, Assistance Publique\u2010H\u00f4pitaux de Paris,Universit\u00e9 Paris\u2010Diderot and INSERM UMR1149,Clichy,France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2016,7,29]]},"reference":[{"issue":"1 Suppl","key":"hep28706-bib-0001-20241017","first-page":"S45","article-title":"Global epidemiology and genotype distribution of the hepatitis C virus","volume":"61","year":"2014","journal-title":"J Hepatol"},{"key":"hep28706-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1111\/j.1365-2893.2012.01650.x","article-title":"Towards realistic estimates of HCV incidence in Egypt","volume":"20","year":"2013","journal-title":"J Viral Hepat"},{"key":"hep28706-bib-0003-20241017","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1111\/j.1365-2893.2006.00823.x","article-title":"Epidemiological characteristics and response to peginterferon plus ribavirin treatment of hepatitis C virus genotype 4 infection","volume":"14","year":"2007","journal-title":"J Viral 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