Elafibranor is a dual peroxisome proliferator-activated receptor (PPAR)‑α/δ agonist known to improve insulin sensitivity, glucose homeostasis, lipid metabolism, and reduce inflammation. This study aimed to evaluate whether elafibranor could induce resolution of nonalcoholic steatohepatitis (NASH) without worsening liver fibrosis. In a randomized controlled trial, patients with NASH were assigned to receive either elafibranor 120 mg/day or placebo. The primary endpoint was the resolution of NASH without fibrosis progression, while secondary endpoints included changes in liver enzymes, lipid profiles, glucose metabolism, and inflammatory markers.

In post hoc analyses, 19% of patients receiving elafibranor achieved NASH resolution without worsening fibrosis, compared to 12% in the placebo group (odds ratio 2.31, 95% CI 1.02–5.24, p = 0.045). Among patients with a NAFLD activity score ≥4, NASH resolution rates were even higher in the elafibranor group (20% vs 11%; modified definition: 19% vs 9%), with odds ratios of 3.16 and 3.52, respectively. Patients who responded to treatment showed a mean reduction in fibrosis stage of 0.65 ± 0.61, whereas nonresponders experienced a mean increase of 0.10 ± 0.98 (p < 0.001). Additionally, elafibranor treatment led to significant improvements in liver function tests, lipid parameters, glucose levels, and systemic inflammatory markers compared to placebo.