{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:39:58Z","timestamp":1790048398886,"version":"4.0.1"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T00:00:00Z","timestamp":1542153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Conatus Pharmaceuticals, Inc."}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Lipotoxicity leading to excessive caspase\u2010mediated apoptosis and inflammation is believed to drive liver damage in NAFLD. Emricasan is a pan\u2010caspase inhibitor that decreased serum ALT and apoptotic and inflammatory markers in subjects with chronic hepatitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To assess whether 28\u00a0days of emricasan would reduce elevated levels of serum ALT, AST, cleaved cytokeratin\u201018, full\u2010length cytokeratin\u201018, and caspase 3\/7 in subjects with NAFLD and raised aminotransferases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Double\u2010blind, placebo\u2010controlled, office\u2010practice study assessed the efficacy, safety, and tolerability of emricasan in subjects with NAFLD and ALT levels \u22651.5 x ULN during screening. Subjects were randomised to emricasan 25\u00a0mg twice daily or matching placebo. Subjects with cirrhosis and other causes for raised aminotransferases were excluded. The primary endpoint was the change in ALT at day 28 in the emricasan group vs placebo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>38 subjects were randomised, 19 each to emricasan or placebo. Baseline disease factors were well balanced except for lower median ALT values in emricasan subjects. Three subjects randomised to placebo discontinued prior to day 28. ALT values decreased significantly in emricasan\u2010treated subjects vs placebo at days 7 (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) and 28 (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.02). cCK18 (day 7), flCK18 (days 7 and 28), and caspase 3\/7 (day 7) were also significantly decreased in emricasan\u2010treated subjects vs placebo. Emricasan treatment was generally safe and well tolerated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Emricasan decreased ALT and biomarkers in subjects with NAFLD and raised aminotransferases after 28\u00a0days. These results support the further development of emricasan in patients with NAFLD. Trial registration: ClinicalTrials.gov, Identifier: NCT02077374.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.15030","type":"journal-article","created":{"date-parts":[[2018,11,15]],"date-time":"2018-11-15T10:29:43Z","timestamp":1542277783000},"page":"64-73","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":113,"title":["Randomised clinical trial: emricasan versus placebo significantly decreases ALT and caspase 3\/7 activation in subjects with non\u2010alcoholic fatty liver disease"],"prefix":"10.1111","volume":"49","author":[{"given":"Mitchell","family":"Shiffman","sequence":"first","affiliation":[{"name":"Liver Institute of Virginia Bon Secours Health System Richmond and Newport News Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley","family":"Freilich","sequence":"additional","affiliation":[{"name":"Kansas City Research Institute Kansas City Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj","family":"Vuppalanchi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Indiana University School of Medicine Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kymberly","family":"Watt","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean L.","family":"Chan","sequence":"additional","affiliation":[{"name":"Conatus Pharmaceuticals Inc. 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