{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:40:23Z","timestamp":1790048423011,"version":"4.0.1"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2018,11,26]],"date-time":"2018-11-26T00:00:00Z","timestamp":1543190400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:p>Caspases play a central role in apoptosis, inflammation, and fibrosis. They produce hemodynamically active, proinflammatory microparticles that cause intrahepatic inflammation, vasoconstriction, and extrahepatic splanchnic vasodilation. Emricasan is a pan\u2010caspase inhibitor that lowers portal hypertension (PH) and improves survival in murine models of cirrhosis. This exploratory study assessed whether emricasan lowers PH in patients with compensated cirrhosis. This multicenter, open\u2010label study enrolled 23 subjects with compensated cirrhosis and PH (hepatic vein pressure gradient [HVPG] &gt;5 mm Hg). Emricasan 25 mg twice daily was given for 28 days. HVPG measurements were standardized and performed before and after emricasan. A single expert read all HVPG tracings. Median age was 59 (range 49\u201080); 70% were male. Cirrhosis etiologies were nonalcoholic steatohepatitis and hepatitis C virus. Subjects were Child class A (87%) with a median Model for End\u2010Stage Liver Disease score of 8 (range 6\u201015). Twelve had severe PH (HVPG \u226512 mm Hg). Overall, there was no significant change in HVPG after emricasan (mean [standard deviation, SD] \u20131.1 [4.57] mm Hg). HVPG decreased significantly (mean [SD] \u20133.7[4.05] mm Hg; <jats:italic toggle=\"yes\">P<\/jats:italic> = 0.003) in those with severe PH: 4\/12 had a \u226520% decrease, 8\/12 had a \u226510% decrease, and 2\/12 HVPG decreased below 12 mm Hg. There were no significant changes in blood pressure or heart rate. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) decreased significantly in the entire group and in those with severe PH. Serum cleaved cytokeratin 18 and caspase\u20103\/7 decreased significantly. Emricasan was well tolerated. One subject discontinued for nonserious adverse events. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Emricasan administered for 28 days decreased HVPG in patients with compensated cirrhosis and severe PH; an effect upon portal venous inflow is likely, and concomitant decreases in AST\/ALT suggest an intrahepatic anti\u2010inflammatory effect.<\/jats:p>","DOI":"10.1002\/hep.30199","type":"journal-article","created":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T12:24:06Z","timestamp":1533126246000},"page":"717-728","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":76,"title":["Emricasan (IDN\u20106556) Lowers Portal Pressure in Patients With Compensated Cirrhosis and Severe Portal Hypertension"],"prefix":"10.1097","volume":"69","author":[{"given":"Guadalupe","family":"Garcia\u2010Tsao","sequence":"first","affiliation":[{"name":"Yale University and VA Connecticut Healthcare System,New Haven,CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Fuchs","sequence":"additional","affiliation":[{"name":"McGuire DVAMC,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell","family":"Shiffman","sequence":"additional","affiliation":[{"name":"Liver Institute of Virginia,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian B.","family":"Borg","sequence":"additional","affiliation":[{"name":"University of Mississippi,Jackson,MS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Pyrsopoulos","sequence":"additional","affiliation":[{"name":"Rutgers New Jersey Medical School,Newark,NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirti","family":"Shetty","sequence":"additional","affiliation":[{"name":"Johns Hopkins Sibley Memorial Hospital,Washington,DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan F.","family":"Gallegos\u2010Orozco","sequence":"additional","affiliation":[{"name":"University of Utah,Salt Lake City,UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Rajender","family":"Reddy","sequence":"additional","affiliation":[{"name":"University of Pennsylvania,Philadelphia,PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyob","family":"Feyssa","sequence":"additional","affiliation":[{"name":"Division of Hepatology,Albert Einstein Medical Center,Philadelphia,PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean L.","family":"Chan","sequence":"additional","affiliation":[{"name":"Conatus Pharmaceuticals,San Diego,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mason","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Conatus Pharmaceuticals,San Diego,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Conatus Pharmaceuticals,San Diego,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred P.","family":"Spada","sequence":"additional","affiliation":[{"name":"Conatus Pharmaceuticals,San Diego,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Hagerty","sequence":"additional","affiliation":[{"name":"Conatus Pharmaceuticals,San Diego,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Bosch","sequence":"additional","affiliation":[{"name":"Liver Unit, Hospital Clinic\u2010IDIBAPS,University of Barcelona,Barcelona,Spain"},{"name":"Swiss Liver, Inselspital,Bern University,Bern,Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2018,11,26]]},"reference":[{"key":"hep30199-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1053\/j.gastro.2007.05.024","article-title":"Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated 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