Improvements in Histologic Features and Diagnosis Associated With Improvement in Fibrosis in Nonalcoholic Steatohepatitis: Results From the Nonalcoholic Steatohepatitis Clinical Research Network Treatment Trials
Year: 2018
Type: article
Abstract: 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) ≥2, 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-point 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-adjusted univariable and multivariable logistic regression models related improvement in fibrosis to improvements in other histologic variables, resolution of steatohepatitis, and improvement in the NAS ≥2. In PIVENS 221 subjects had baseline and 96-week biopsies, and in FLINT 200 subjects had baseline and 72-week 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] 2.0-7.6; P < 0.001; FLINT, OR, 8.0; 95% CI 3.1-20.9; P < 0.001), and improved NAS by ≥2 (PIVENS, OR, 2.4; 95% CI 1.3-4.3; P = 0.003; FLINT, OR, 4.2; 95% CI 2.1-8.3; P < 0.001). Improvement in histologic features associated with improved fibrosis for both studies included steatosis, ballooning, Mallory-Denk bodies, and portal, but not lobular, inflammation. Conclusion: These findings support a strong link between histologic resolution of steatohepatitis with improvement in fibrosis in NASH.
Source: Hepatology
DOI: 10.1002/hep.30418
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Continuation of the Nonalcoholic Steatohepatitis Clinical Research Network, San Diego Clinical and Translational Research Institute, Institute of Translational Health Sciences, Duke CTSA, Center for Clinical and Translational Research, Center for Clinical and Translational Research, Clinical and Translational Science Institute, Washington University Institute of Clinical and Translational Sciences, Indiana Clinical and Translational Sciences Institute, Indiana Clinical and Translational Sciences Institute, Indiana Clinical and Translational Science Institute (UL1), Clinical and Translational Science Collaborative of Cleveland, Clinical and Translational Science Collaborative of Cleveland, UC San Diego Clinical and Translational Research Institute, Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN), Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN), Data Coordinating Center for the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Continuation, Clinical Research Network in Nonalcoholic Steatohepatitis, Collaborative Clinical Research in Nonalcoholic Steatohepatitis, Washington University Institute of Clinical and Translational Sciences, Institute of Translational Health Sciences, Continuation of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Clinical Center-Cleveland site, Clinical Research on Nonalcoholic Fatty Liver Disease, The Saint Louis University Component of the NASH Clinical Research Network, Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)
OpenAlex ID: W2903966071