Dual peroxisome proliferator-activated receptor α/δ agonists: Hope for the treatment of alcohol-associated liver disease?

Abstract

In this letter, we review the article “Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease”. We focus specifically on the detrimental effects of alcohol-associated liver disease (ALD) on human health. Given its insidious onset and increasing incidence, increasing awareness of ALD can contribute to reducing the prevalence of liver diseases. ALD comprises a spectrum of several different disorders, including liver steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The pathogenesis of ALD is exceedingly complex. Previous studies have shown that peroxisome proliferator-activated receptors (PPARs) regulate lipid metabolism, glucose homeostasis and inflammatory responses within the organism. Additionally, their dysfunction is a major contributor to the progression of ALD. Elafibranor is an oral, dual PPARα and δ agonist. The effectiveness of elafibranor in the treatment of ALD remains unclear. In this letter, we emphasize the harm of ALD and the burden it places on society. Furthermore, we summarize the clinical management of all stages of ALD and present new insights into its pathogenesis and potential therapeutic targets. Additionally, we discuss the mechanisms of action of PPARα and δ agonists, the significance of their antifibrotic effects on ALD and future research directions.

Keywords: Alcohol-associated liver disease; Fibrosis; Antifibrotic effect; Elafibranor; Peroxisome proliferator-activated receptor

Core Tip: Alcohol-associated liver disease (ALD) is a common disease with an annually increasing incidence. It is the primary cause of cirrhosis and mortality due to hepatopathy in patients from many regions worldwide. Chronic liver damage resulting from prolonged excessive alcohol consumption can lead to liver fibrosis, which may progress to cirrhosis and hepatocellular carcinoma. Strengthening awareness of the risks associated with ALD, abstaining from alcohol, and implementing early intervention are fundamental to the management of ALD.