{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:13:06Z","timestamp":1787501586209,"version":"build-2736575974"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T00:00:00Z","timestamp":1551916800000},"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":[[2019,8]]},"abstract":"<jats:p>\n                    Hepatocellular injury and inflammation are believed to be the primary drivers of fibrogenesis that ultimately lead to cirrhosis in patients with nonalcoholic steatohepatitis (NASH). This study sought associations between observed improvements in fibrosis with improvement in specific histologic features, nonalcoholic fatty liver disease activity score (NAS) \u22652, diagnostic category, and primary histologically based outcomes of two adult NASH treatment trials. The primary outcome for the study was fibrosis improvement from baseline to end of treatment, defined as a 1\u2010point or more improvement in fibrosis stage. This is a retrospective analysis of biopsy data collected from the NASH Clinical Research Network Pathology Committee of Pioglitazone versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with NASH Trial (PIVENS) and Farnesoid X Receptor Ligand Obeticholic Acid in NASH Treatment Trial (FLINT) baseline and final biopsies. Treatment group\u2013adjusted univariable and multivariable logistic regression models related improvement in fibrosis to improvements in other histologic variables, resolution of steatohepatitis, and improvement in the NAS \u22652. In PIVENS 221 subjects had baseline and 96\u2010week biopsies, and in FLINT 200 subjects had baseline and 72\u2010week biopsies. Improvement in fibrosis was found in 38% of PIVENS and 29% of FLINT biopsies; fibrosis improvement was more likely in treated than placebo subjects in both studies. Controlling for treatment group, fibrosis improvement was associated most strongly with resolution of NASH (PIVENS, odds ratio [OR], 3.9; 95% confidence interval [CI] 2.0\u20107.6;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0&lt;\u00a00.001; FLINT, OR, 8.0; 95% CI 3.1\u201020.9;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0&lt;\u00a00.001), and improved NAS by \u22652 (PIVENS, OR, 2.4; 95% CI 1.3\u20104.3;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0=\u00a00.003; FLINT, OR, 4.2; 95% CI 2.1\u20108.3;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0&lt;\u00a00.001). Improvement in histologic features associated with improved fibrosis for both studies included steatosis, ballooning, Mallory\u2010Denk bodies, and portal, but not lobular, inflammation.\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    These findings support a strong link between histologic resolution of steatohepatitis with improvement in fibrosis in NASH.\n                  <\/jats:p>","DOI":"10.1002\/hep.30418","type":"journal-article","created":{"date-parts":[[2018,12,14]],"date-time":"2018-12-14T08:10:12Z","timestamp":1544775012000},"page":"522-531","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":142,"title":["Improvements in Histologic Features and Diagnosis Associated With Improvement in Fibrosis in Nonalcoholic Steatohepatitis: Results From the Nonalcoholic Steatohepatitis Clinical Research Network Treatment Trials"],"prefix":"10.1097","volume":"70","author":[{"given":"Elizabeth M.","family":"Brunt","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology,Washington University School of Medicine,St. Louis,MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Kleiner","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology,National Cancer Institute,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Johns Hopkins University,Baltimore,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun J.","family":"Sanyal","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University School of Medicine,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent A.","family":"Neuschwander\u2010Tetri","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Saint Louis University School of Medicine,St. Louis,MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Nonalcoholic Steatohepatitis Clinical Research Network","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2019,3,7]]},"reference":[{"key":"hep30418-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1053\/j.gastro.2014.11.039","article-title":"Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States","volume":"148","year":"2015","journal-title":"Gastroenterology"},{"key":"hep30418-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.2337\/diabetes.50.8.1844","article-title":"Nonalcoholic fatty liver disease: a feature of the metabolic 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