{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T01:08:16Z","timestamp":1773709696117,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,11,29]],"date-time":"2016-11-29T00:00:00Z","timestamp":1480377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hepatitis C virus (<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>) infection is a leading cause of liver cirrhosis and subsequent hepatocellular carcinoma. <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> genotype 4 is found widely in the Middle East, Egypt and Africa, and has also spread into Europe. There are limited data available regarding the use of direct\u2010acting antiviral agents in <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> genotype 4\u2010infected patients with cirrhosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To evaluate in the phase <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content>, open\u2010label, single\u2010arm <jats:styled-content style=\"fixed-case\">PLUTO<\/jats:styled-content> study the efficacy and safety of 12 weeks of simeprevir (<jats:styled-content style=\"fixed-case\">HCV NS<\/jats:styled-content>3\/4A protease inhibitor) plus sofosbuvir (<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> nucleotide\u2010analogue <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>5B polymerase inhibitor) in treatment\u2010na\u00efve and (peg)interferon \u00b1 ribavirin\u2010experienced <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> genotype 4\u2010infected patients, with or without compensated cirrhosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult patients with chronic <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> genotype 4 infection received simeprevir 150 mg once\u2010daily and sofosbuvir 400 mg once\u2010daily for 12 weeks. The primary efficacy endpoint was sustained virologic response 12 weeks after the end of treatment (<jats:styled-content style=\"fixed-case\">SVR<\/jats:styled-content>12). Safety was also assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Forty patients received treatment; the majority were male (73%) and treatment\u2010experienced (68%). Overall, 7\/40 (18%) patients had compensated cirrhosis. All patients achieved <jats:styled-content style=\"fixed-case\">SVR<\/jats:styled-content>12 [100% (Clopper\u2010Pearson 95% confidence interval: 91\u2013100%)]. Adverse events, all Grade 1 or 2, were reported in 20\/40 (50%) patients. No serious adverse events were reported and no patients discontinued study treatment. Grade 3 treatment\u2010emergent laboratory abnormalities were noted in 2\/40 (5%) patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Treatment with simeprevir plus sofosbuvir for 12 weeks resulted in <jats:styled-content style=\"fixed-case\">SVR<\/jats:styled-content>12 rates of 100% in treatment\u2010na\u00efve and \u2010experienced patients with <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> genotype 4 infection with or without compensated cirrhosis, and was well tolerated. [<jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>02250807]<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.13883","type":"journal-article","created":{"date-parts":[[2016,11,29]],"date-time":"2016-11-29T06:12:47Z","timestamp":1480399967000},"page":"468-475","source":"Crossref","is-referenced-by-count":26,"title":["Simeprevir in combination with sofosbuvir in treatment\u2010na\u00efve and \u2010experienced patients with hepatitis C virus genotype 4 infection: a Phase <scp>III<\/scp>, open\u2010label, single\u2010arm study (<scp>PLUTO<\/scp>)"],"prefix":"10.1111","volume":"45","author":[{"given":"M.","family":"Buti","sequence":"first","affiliation":[{"name":"Hospital Vall d'Hebron and Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd) Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. L.","family":"Calleja","sequence":"additional","affiliation":[{"name":"University Hospital Puerta de Hierro Majadahonda Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Lens","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd) Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Diago","sequence":"additional","affiliation":[{"name":"Quir\u00f3n Valencia Hospital Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Ortega","sequence":"additional","affiliation":[{"name":"Consorcio Hospital General Universitario de Valencia Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Crespo","sequence":"additional","affiliation":[{"name":"Hospital Universitario Marques de Valdecilla Santander Cantabria Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Planas","sequence":"additional","affiliation":[{"name":"Hospital Universitari Germans Trias i Pujol (CIBERehd) Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Romero\u2010G\u00f3mez","sequence":"additional","affiliation":[{"name":"Valme University Hospital University of Seville Sevilla Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F. 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