Therapeutic potential of elafibranor in alcohol-associated liver disease: Insights into macrophage modulation and fibrosis reduction

Figure 1 Mechanistic pathways of elafibranor in alcohol-associated liver disease. Elafibranor (EFN) exerts its therapeutic effects through dual activation of peroxisome proliferator-activated receptor (PPAR)α and PPARδ. PPARα activation reduces oxidative stress and inflammation by modulating Kupffer cell polarization and suppressing pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). Concurrently, PPARδ activation enhances mitochondrial biogenesis, β-oxidation, and lipid metabolism, counteracting hepatic steatosis. EFN also strengthens the gut barrier by limiting lipopolysaccharides and pathogen-associated molecular patterns translocation, thereby reducing systemic inflammation and liver injury. Moreover, EFN inhibits hepatic stellate cell activation, thereby attenuating fibrosis progression. These multifaceted actions position EFN as a promising therapeutic strategy for alcohol-associated liver disease, addressing both metabolic dysfunction and immune-mediated fibrosis. EFN: Elafibranor; ALD: Alcohol-associated liver disease; TNF-α: Tumor necrosis factor-alpha; IL: Interleukin; PPAR: Peroxisome proliferator-activated receptor; LPS: Lipopolysaccharides; HSC: Hepatic stellate cells.