{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T20:26:07Z","timestamp":1773951967264,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,11,23]],"date-time":"2016-11-23T00:00:00Z","timestamp":1479859200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"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":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Approximately three million individuals in the United States are chronically infected with hepatitis C virus (<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>). Chronic <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> infection may lead to the development of compensated as well as decompensated liver cirrhosis. The Phase <jats:styled-content style=\"fixed-case\">II IMPACT<\/jats:styled-content> study was conducted in <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> genotype 1\u2010 or 4\u2010infected cirrhotic patients with portal hypertension or decompensated liver disease and assessed for the first time the combination of the three direct\u2010acting antivirals simeprevir, daclatasvir and sofosbuvir. Treatment\u2010na\u00efve or treatment\u2010experienced adults with Child\u2010Pugh (<jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>) score &lt;7 (<jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content> A) and evidence of portal hypertension, or <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content> score 7\u20139 (<jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content> B), received 12\u00a0weeks of simeprevir 150\u00a0mg, daclatasvir 60\u00a0mg and sofosbuvir 400\u00a0mg, once daily. The primary efficacy endpoint was sustained virologic response 12\u00a0weeks after end of treatment (<jats:styled-content style=\"fixed-case\">SVR<\/jats:styled-content>12). Pharmacokinetics and safety were also assessed. Overall, 40 patients were enrolled (<jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content> A: 19; <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content> B: 21). All 40 patients achieved <jats:styled-content style=\"fixed-case\">SVR<\/jats:styled-content>12. At week 8, the mean pharmacokinetic exposure to simeprevir, sofosbuvir, daclatasvir and <jats:styled-content style=\"fixed-case\">GS<\/jats:styled-content>\u2010331007 (sofosbuvir metabolite) was 2.2\u2010, 1.5\u2010, 1.2\u2010 and 1.2\u2010fold higher in patients with <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content> B than <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content> A, respectively. Grade 1\/2 adverse events (<jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s) occurred in 26 of 40 (65%) patients. One <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content> B patient had a Grade 3 <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content> (gastrointestinal haemorrhage), which was reported as a serious <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content> but not considered related to study drugs. Treatment for 12\u00a0weeks with simeprevir, daclatasvir and sofosbuvir was generally safe and well tolerated, and resulted in 100% of cirrhotic patients with portal hypertension or decompensated liver disease achieving <jats:styled-content style=\"fixed-case\">SVR<\/jats:styled-content>12.<\/jats:p>","DOI":"10.1111\/jvh.12645","type":"journal-article","created":{"date-parts":[[2016,11,23]],"date-time":"2016-11-23T06:26:43Z","timestamp":1479882403000},"page":"287-294","source":"Crossref","is-referenced-by-count":26,"title":["Simeprevir, daclatasvir and sofosbuvir for hepatitis C virus\u2010infected patients with decompensated liver disease"],"prefix":"10.1111","volume":"24","author":[{"given":"E.","family":"Lawitz","sequence":"first","affiliation":[{"name":"Texas Liver Institute University of Texas Health Science Center  San Antonio TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Poordad","sequence":"additional","affiliation":[{"name":"Texas Liver Institute University of Texas Health Science Center  San Antonio TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. A.","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"Texas Liver Institute University of Texas Health Science Center  San Antonio TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. N.","family":"Kakuda","sequence":"additional","affiliation":[{"name":"Alios Biopharma  San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Picchio","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development LLC  Raritan NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Beets","sequence":"additional","affiliation":[{"name":"Janssen Pharmaceutica NV  Beerse Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Vandevoorde","sequence":"additional","affiliation":[{"name":"Janssen Pharmaceutica NV  Beerse Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Van Remoortere","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development LLC  Titusville NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Jacquemyn","sequence":"additional","affiliation":[{"name":"Janssen Pharmaceutica NV  Beerse Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Luo","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development LLC  Titusville NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Ouwerkerk\u2010Mahadevan","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development LLC  Beerse Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Vijgen","sequence":"additional","affiliation":[{"name":"Janssen Pharmaceutica NV  Beerse Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Van Eygen","sequence":"additional","affiliation":[{"name":"Janssen Pharmaceutica NV  Beerse Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Beumont","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development LLC  Beerse Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,11,23]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"US Food and Drug Administration.Chronic hepatitis C virus infection: developing direct\u2010acting antiviral drugs for treatment.2016.http:\/\/www.fda.gov\/downloads\/Drugs\/GuidanceComplianceRegulatoryInformation\/Guidances\/UCM225333.pdf. 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