{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T17:28:20Z","timestamp":1792258100696,"version":"4.4.0"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","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":[],"crossmark-restriction":false},"short-container-title":["Liver Transpl"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:p>Hepatitis C virus (HCV) entry inhibitors have been hypothesized to prevent infection of the liver after transplantation. ITX5061 is a scavenger receptor class B type I antagonist that blocks HCV entry and infection in vitro. We assessed the safety and efficacy of ITX5061 to limit HCV infection of the graft. The study included 23 HCV\u2010infected patients undergoing liver transplantation. The first 13 \u201ccontrol\u201d patients did not receive drug. The subsequent 10 patients received 150\u2009mg of ITX5061 immediately before and after transplant and daily for 1 week thereafter. ITX5061 pharmacokinetics and plasma HCV RNA were quantified. Viral genetic diversity was measured by ultradeep pyrosequencing (UDPS). ITX5061 was well tolerated with measurable plasma concentrations during therapy. Although the median HCV RNA reduction was greater in ITX\u2010treated patients at all time points in the first week after transplantation, there was no difference in the overall change in the area over the HCV RNA curve in the 7\u2010day treatment period. However, in genotype (GT) 1\u2013infected patients, treatment was associated with a sustained reduction in HCV RNA levels compared to the control group (area over the HCV RNA curve analysis, <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20090.004). UDPS revealed a complex and evolving pattern of HCV variants infecting the graft during the first week. ITX5061 significantly limited viral evolution where the median divergence between day 0 and day 7 was 3.5% in the control group compared to 0.1% in the treated group. In conclusion, ITX5061 reduces plasma HCV RNA after transplant notably in GT 1\u2013infected patients and slows viral evolution. Following liver transplantation, the likely contribution of extrahepatic reservoirs of HCV necessitates combining entry inhibitors such as ITX5061 with inhibitors of replication in future studies. <jats:italic toggle=\"yes\">Liver Transpl 22:287\u2010297, 2016<\/jats:italic>. \u00a9 2015 AASLD.<\/jats:p>","DOI":"10.1002\/lt.24349","type":"journal-article","created":{"date-parts":[[2015,10,5]],"date-time":"2015-10-05T23:10:04Z","timestamp":1444086604000},"page":"287-297","source":"Crossref","is-referenced-by-count":32,"title":["Effect of scavenger receptor class B type I antagonist ITX5061 in patients with hepatitis C virus infection undergoing liver transplantation"],"prefix":"10.1097","volume":"22","author":[{"given":"Ian A.","family":"Rowe","sequence":"first","affiliation":[{"name":"Viral Hepatitis Laboratory, Centre for Human Virology"},{"name":"National Institute for Health Research Birmingham Liver Biomedical Research Unit"},{"name":"Liver and Hepatobiliary Unit, Queen Elizabeth Hospital Birmingham,Birmingham,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien C.","family":"Tully","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT and Harvard,Cambridge,MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Armstrong","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Birmingham Liver Biomedical Research Unit"},{"name":"Liver and Hepatobiliary Unit, Queen Elizabeth Hospital Birmingham,Birmingham,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Parker","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Birmingham Liver Biomedical Research Unit"},{"name":"Liver and Hepatobiliary Unit, Queen Elizabeth Hospital Birmingham,Birmingham,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Guo","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Birmingham Liver Biomedical Research Unit"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Barton","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Birmingham Liver Biomedical Research Unit"},{"name":"Cancer Research UK Clinical Trials Unit,University of Birmingham,Birmingham,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gene D.","family":"Morse","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, and New York State Center of Excellence in Bioinformatics and Life Sciences,University at Buffalo, State University of New York,Buffalo,NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles S.","family":"Venuto","sequence":"additional","affiliation":[{"name":"Center for Human Experimental Therapeutics,University of Rochester School of Medicine,Rochester,NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin B.","family":"Ogilvie","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT and Harvard,Cambridge,MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ditte L.","family":"Hedegaard","sequence":"additional","affiliation":[{"name":"Viral Hepatitis Laboratory, Centre for Human Virology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey F.","family":"McKelvy","sequence":"additional","affiliation":[{"name":"iTherX Pharma Inc.,San Diego,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flossie","family":"Wong\u2010Staal","sequence":"additional","affiliation":[{"name":"iTherX Pharma Inc.,San Diego,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd M.","family":"Allen","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT and Harvard,Cambridge,MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Balfe","sequence":"additional","affiliation":[{"name":"Viral Hepatitis Laboratory, Centre for Human Virology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane A.","family":"McKeating","sequence":"additional","affiliation":[{"name":"Viral Hepatitis Laboratory, Centre for Human Virology"},{"name":"National Institute for Health Research Birmingham Liver Biomedical Research Unit"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Mutimer","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Birmingham Liver Biomedical Research Unit"},{"name":"Liver and Hepatobiliary Unit, Queen Elizabeth Hospital Birmingham,Birmingham,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,2,25]]},"reference":[{"key":"lt24349-bib-0001-20240115","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.jhep.2012.04.015","article-title":"Evolution of indications and results of liver transplantation in Europe. 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