Elafibranor: A promising therapeutic approach for liver fibrosis and gut barrier dysfunction in alcohol-associated liver disease

Abstract

This article discusses the recent study written by Koizumi et al. Alcohol-associated liver disease (ALD) is a major cause of liver-related morbidity and mortality, which is driven by complex mechanisms, including lipid accumulation, apoptosis, and inflammatory responses exacerbated by gut barrier dysfunction. The study explored the therapeutic potential of elafibranor, a dual peroxisome proliferator-activated receptor alpha/delta agonist. In clinical trials, elafibranor has shown promise for the treatment of other liver conditions; however, its effects on ALD remain unclear. The authors’ findings indicate that elafibranor significantly reduced liver fibrosis and enhanced gut barrier integrity in patients with ALD. These positive effects of elafibranor are mediated through multiple pathways. Elafibranor promotes lipid metabolism, reduces oxidative stress, and inhibits inflammatory responses by restoring gut barrier function. Specifically, it improves hepatocyte function by enhancing autophagic and antioxidant capacity, and it mitigates inflammation by suppressing the lipopolysaccharide/toll-like receptor 4/nuclear factor kappa B signaling pathway. These findings indicate that elafibranor has promising clinical applications. In addition, the study highlights elafibranor’s potential as a therapeutic agent for liver diseases, particularly ALD. This article underscores the importance of understanding the mechanistic pathways underlying ALD and suggests directions for future research aimed at elucidating the benefits and limitations of elafibranor.

Keywords: Elafibranor; Liver fibrosis; Gut barrier function; Alcohol-associated liver disease; Peroxisome proliferator-activated receptor agonists

Core Tip: This article highlights the major findings of the study written by Koizumi et al. The study demonstrated the potential of elafibranor, a peroxisome proliferator-activated receptor agonist, in mitigating liver fibrosis and improving gut barrier integrity in a mouse model of alcohol-associated liver disease. These findings underscore the promising therapeutic potential of elafibranor and its relevance in advancing treatment strategies for liver diseases linked to chronic alcohol consumption.