Improvement of non-invasive tests of liver steatosis and fibrosis as indicators for nonalcoholic fatty liver disease in type 2 diabetes mellitus patients with elevated cardiovascular risk profile using the PPAR-α/γ agonist aleglitazar

Esmée J. Grobbee, Vivian D. de Jong*, Ilse C. Schrieks, Maarten E. Tushuizen, Adriaan G. Holleboom, Jean Claude Tardif, A. Michael Lincoff, Gregory G. Schwartz, Manuel Castro Cabezas, Diederick E. Grobbee

*Corresponding author for this work

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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.

Original languageEnglish
Article numbere0277706
JournalPLoS ONE
Volume17
Issue number11
DOIs
Publication statusPublished - 15 Nov 2022

Bibliographical note

Funding Information:
The author(s) received no specific funding for this work. The original AleCardio trial was sponsored by F. Hoffmann-La Roche (Basel, Switzerland). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors acknowledge the AleCardio steering committee for their permission to use the data in order to perform the current study.

Publisher Copyright:
© 2022 Grobbee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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