{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T18:32:27Z","timestamp":1794508347420,"version":"4.9.1"},"reference-count":18,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T00:00:00Z","timestamp":1644192000000},"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":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Surrogate endpoints that predict complications are necessary for assessment and approval of NASH therapies. We assessed associations between histologic and noninvasive tests (NITs) of fibrosis with liver\u2010related complications in patients with NASH cirrhosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results<\/jats:title>\n                    <jats:p>\n                      Patients with compensated cirrhosis due to NASH were enrolled in two placebo\u2010controlled trials of simtuzumab and selonsertib. Liver fibrosis at baseline and week 48 (W48) was staged by NASH Clinical Research Network (CRN) and Ishak classifications and a machine learning (ML) approach, hepatic collagen and alpha\u2010smooth muscle actin (\u03b1\u2010SMA) expression were quantified by morphometry, liver stiffness (LS) was measured by transient elastography, and serum NITs (enhanced liver fibrosis [ELF], NAFLD fibrosis score [NFS], and Fibrosis\u20104 index [FIB\u20104]) were calculated. Cox regression determined associations between these parameters at baseline and their changes over time with adjudicated liver\u2010related clinical events. Among 1,135 patients, 709 (62%) had Ishak stage 6 fibrosis, and median ELF and LS were 10.66 and 21.1 kPa, respectively. During a median follow\u2010up of 16.6 months, 71 (6.3%) had a liver\u2010related event; associated baseline factors included Ishak stage 6 fibrosis, and higher hepatic collagen, \u03b1\u2010SMA expression, ML\u2010based fibrosis parameters, LS, ELF, NFS, and FIB\u20104. Cirrhosis regression observed in 16% (176\/1,135) between BL and W48 was associated with a lower risk of events versus nonregression (1.1% [2\/176] vs. 7.2% [69\/957]; HR, 0.16; 95% CI, 0.04, 0.65 [\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.0104]). Conversely, after adjustment for baseline values, increases in hepatic collagen, \u03b1\u2010SMA, ML\u2010based fibrosis parameters, NFS, and LS were associated with an increased risk of events.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients with compensated cirrhosis due to NASH, regression of fibrosis is associated with a reduction in liver\u2010related complications. These data support the utility of histologic fibrosis regression and NITs as clinical trial endpoints for NASH cirrhosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.32204","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T15:54:14Z","timestamp":1634745254000},"page":"1235-1246","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":164,"title":["Cirrhosis regression is associated with improved clinical outcomes in patients with nonalcoholic steatohepatitis"],"prefix":"10.1097","volume":"75","author":[{"given":"Arun J.","family":"Sanyal","sequence":"first","affiliation":[{"name":"Virginia Commonwealth University,Richmond,Virginia,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9518-0088","authenticated-orcid":false,"given":"Quentin M.","family":"Anstee","sequence":"additional","affiliation":[{"name":"Translational & Clinical Research Institute,Faculty of Medical Sciences,Newcastle University,Newcastle upon Tyne,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Trauner","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Medical University of Vienna,Vienna,Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J.","family":"Lawitz","sequence":"additional","affiliation":[{"name":"Texas Liver Institute,University of Texas Health San Antonio,San Antonio,Texas,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manal F.","family":"Abdelmalek","sequence":"additional","affiliation":[{"name":"Duke University Medical Center,Durham,North Carolina,USA"},{"name":"Indiana University Medical Center,Indianapolis,Indiana,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dora","family":"Ding","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc.,Foster City,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Han","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc.,Foster City,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Jia","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc.,Foster City,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan S.","family":"Huss","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc.,Foster City,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuhan","family":"Chung","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc.,Foster City,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2215-9410","authenticated-orcid":false,"given":"Vincent Wai\u2010Sun","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics,The Chinese University of Hong Kong,Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Okanoue","sequence":"additional","affiliation":[{"name":"Saiseikai Suita Hospital,Suita City, Osaka,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Romero\u2010Gomez","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine of Seville,Virgen del Rocio University Hospital,University of Seville,Sevilla,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0206-1179","authenticated-orcid":false,"given":"Andrew J.","family":"Muir","sequence":"additional","affiliation":[{"name":"Duke University Medical Center,Durham,North Carolina,USA"},{"name":"Indiana University Medical Center,Indianapolis,Indiana,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nezam H.","family":"Afdhal","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center and Harvard Medical School,Boston,Massachusetts,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Bosch","sequence":"additional","affiliation":[{"name":"Hospital Clinic\u2010IDIBAPS,University of Barcelona,Barcelona,Spain"},{"name":"Department of Biomedical Research,Bern University,Bern,Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Goodman","sequence":"additional","affiliation":[{"name":"Inova Fairfax Medical Campus,Falls Church,Virginia,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A.","family":"Harrison","sequence":"additional","affiliation":[{"name":"Pinnacle Clinical Research,San 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