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Abstract Details
Improvement of non-invasive tests of liver steatosis and fibrosis as indicators for non-alcoholic fatty liver disease in type 2 diabetes mellitus patients with elevated cardiovascular risk profile using the PPAR-a/? agonist aleglitazar
PLoS One. 2022 Nov 15;17(11):e0277706.doi: 10.1371/journal.pone.0277706. eCollection 2022.
1Department of Gastroenterology and Hepatology, Erasmus MC Medical Center, Rotterdam, The Netherlands.
2Julius Global Health, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
3Julius Clinical, Zeist, The Netherlands.
4Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands.
5Department of Vascular Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands.
6Montreal Heart Institute Coordinating Center, Université de Montréal, Montreal, Canada.
7Department of Cardiovascular Medicine, Cleveland Clinic Coordinating Center for Clinical Research (C5Research), Cleveland, OH, United States of America.
8Division of Cardiology, VA Medical Center and University of Colorado School of Medicine, Denver, CO, United States of America.
9Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands.
10Department of Endocrinology, Erasmus MC Medical Center, Rotterdam, The Netherlands.
Abstract
Background: Peroxisome proliferator-activated receptor (PPAR) agonists may have favorable outcomes on non-alcoholic fatty liver disease. This study serves as proof of concept to evaluate whether dual PPAR-α/γ agonists improve non-invasive tests of liver steatosis and fibrosis.
Methods: This is a post-hoc analysis of a randomized, double-blind, placebo-controlled, multi-center trial comprising 7226 patients with type 2 diabetes mellitus and recent coronary artery disease randomized to receive aleglitazar, a PPAR-α/γ agonists, or placebo for two years. Main outcomes were change in non-invasive tests for liver steatosis and fibrosis: Liver Fat Score (LFS), Liver Accumulation Product (LAP), Fibrosis-4 (FIB-4), and NAFLD Fibrosis Score (NFS).
Results: LFS, LAP and FIB-4 decreased upon treatment, whereas scores in the placebo group remained the same or increased (P<0.001). NFS responded differently but remained consistently lower than placebo. In the treatment group more participants shifted to a lower FIB-4 and NFS category, or improved in respect to the LAP cut-off values compared to the placebo group (P<0.001 for FIB-4 and LAP, P<0.004 for NFS). LFS had a low discriminative power in this study.
Conclusion: This post-hoc analysis showed improvement of non-invasive tests of liver steatosis and fibrosis after starting dual PPAR-α/γ agonist treatment, adding to the evidence that this pathway has potential in non-alcoholic fatty liver disease treatment.