Elafibranor, a dual PPARα and PPARδ agonist, reduces alcohol-associated liver disease: Lessons from a mouse model

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent liver pathology in need of novel pharmacological treatments to complement lifestyle-based interventions. Nuclear receptor agonists have been under scrutiny as potential pharmacological targets and as of today, resmetirom, a thyroid hormone receptor b agonist, is the only approved agent. The dual PPAR α and δ agonist elafibranor has also undergone extensive clinical testing, which reached the phase III clinical trial but failed to demonstrate a beneficial effect on MASLD. As alcohol-associated liver disease and MASLD can be interconnected, whether elafibranor might be affective against liver disease caused by alcohol consumption is worth investigating. Writing recently in the World Journal of Gastroenterology , Koizumi et al reported using a mouse model of alcohol-associated liver disease and found that hepatic steatosis, liver fibrosis, and hepatocyte apoptosis were alleviated by administration of elafibranor. Although preclinical in nature, these data support the potential beneficial action of elafibranor in alcohol-induced MASLD, warranting the testing of this molecule in patients with steatotic liver disease caused by alcohol consumption.