{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:15:54Z","timestamp":1791908154775,"version":"4.3.4"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2021,2,15]],"date-time":"2021-02-15T00:00:00Z","timestamp":1613347200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"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":[[2021,2]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Advanced fibrosis attributable to NASH is a leading cause of end\u2010stage liver disease.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>In this phase 2b trial, 392 patients with bridging fibrosis or compensated cirrhosis (F3\u2010F4) were randomized to receive placebo, selonsertib 18\u00a0mg, cilofexor 30\u00a0mg, or firsocostat 20\u00a0mg, alone or in two\u2010drug combinations, once\u2010daily for 48\u00a0weeks. The primary endpoint was a \u22651\u2010stage improvement in fibrosis without worsening of NASH between baseline and 48\u00a0weeks based on central pathologist review. Exploratory endpoints included changes in NAFLD Activity Score (NAS), liver histology assessed using a machine learning (ML) approach, liver biochemistry, and noninvasive markers. The majority had cirrhosis (56%) and NAS \u22655 (83%). The primary endpoint was achieved in 11% of placebo\u2010treated patients versus cilofexor\/firsocostat (21%; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.17), cilofexor\/selonsertib (19%; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.26), firsocostat\/selonsertib (15%; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.62), firsocostat (12%; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.94), and cilofexor (12%; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.96). Changes in hepatic collagen by morphometry were not significant, but cilofexor\/firsocostat led to a significant decrease in ML NASH CRN fibrosis score (<jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.040) and a shift in biopsy area from F3\u2010F4 to \u2264F2 fibrosis patterns. Compared to placebo, significantly higher proportions of cilofexor\/firsocostat patients had a \u22652\u2010point NAS reduction; reductions in steatosis, lobular inflammation, and ballooning; and significant improvements in alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, bile acids, cytokeratin\u201018, insulin, estimated glomerular filtration rate, ELF score, and liver stiffness by transient elastography (all <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0\u2264\u00a00.05). Pruritus occurred in 20%\u201029% of cilofexor versus 15% of placebo\u2010treated patients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>In patients with bridging fibrosis and cirrhosis, 48\u00a0weeks of cilofexor\/firsocostat was well tolerated, led to improvements in NASH activity, and may have an antifibrotic effect. This combination offers potential for fibrosis regression with longer\u2010term therapy in patients with advanced fibrosis attributable to NASH.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31622","type":"journal-article","created":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T05:34:41Z","timestamp":1604986481000},"page":"625-643","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":284,"title":["Combination Therapies Including Cilofexor and Firsocostat for Bridging Fibrosis and Cirrhosis Attributable to NASH"],"prefix":"10.1097","volume":"73","author":[{"given":"Rohit","family":"Loomba","sequence":"first","affiliation":[{"name":"NAFLD Research Center,University of California at San Diego,La Jolla,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazen","family":"Noureddin","sequence":"additional","affiliation":[{"name":"Fatty Liver Program,Cedars\u2010Sinai Medical Center,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kris V.","family":"Kowdley","sequence":"additional","affiliation":[{"name":"Liver Institute Northwest,Seattle,WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Kohli","sequence":"additional","affiliation":[{"name":"Arizona Liver Health,Chandler,AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aasim","family":"Sheikh","sequence":"additional","affiliation":[{"name":"GI Specialists of Georgia,Marietta,GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Neff","sequence":"additional","affiliation":[{"name":"Covenant Research, LLC,Sarasota,FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bal Raj","family":"Bhandari","sequence":"additional","affiliation":[{"name":"Delta Research Partners, LLC,Bastrop,LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadege","family":"Gunn","sequence":"additional","affiliation":[{"name":"Pinnacle Clinical Research,Austin,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen H.","family":"Caldwell","sequence":"additional","affiliation":[{"name":"University of Virginia,Charlottesville,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Goodman","sequence":"additional","affiliation":[{"name":"Inova Fairfax Hospital,Falls Church,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilan","family":"Wapinski","sequence":"additional","affiliation":[{"name":"PathAI,Boston,MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murray","family":"Resnick","sequence":"additional","affiliation":[{"name":"PathAI,Boston,MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew H.","family":"Beck","sequence":"additional","affiliation":[{"name":"PathAI,Boston,MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dora","family":"Ding","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc.,Foster City,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Jia","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc.,Foster City,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jen\u2010Chieh","family":"Chuang","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc.,Foster City,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan S.","family":"Huss","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc.,Foster City,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuhan","family":"Chung","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc.,Foster City,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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