Therapeutic implications of obeticholic acid, a farnesoid X receptor agonist, in the treatment of liver fibrosis

Abstract

Liver fibrosis, a serious consequence of chronic liver disease, is characterized by excessive extracellular matrix (ECM) accumulation and impaired liver function. Obeticholic acid (OCA) is an agonist of the farnesoid X receptors (FXRs) that modulates multiple pathways, including bile acid and lipid metabolism, intestinal microbiome balance, and inflammatory responses. Recently, OCA has been investigated as a treatment for liver fibrosis. This review emphasizes the therapeutic potential of OCA and explores the complex cellular and molecular mechanisms underlying liver fibrosis. Furthermore, the review summarizes preclinical and clinical data on OCA, highlighting significant milestones in its development for primary biliary cholangitis and metabolic dysfunction-associated steatohepatitis. While OCA shows promise in improving liver fibrosis, its clinical use is limited by safety concerns, regulatory challenges, and adverse events, including dose-dependent pruritus, elevated LDL cholesterol, gallstones, and potential hepatotoxicity. Consequently, combination therapy strategies are being evaluated to increase therapeutic outcomes and minimize side effects. This reflects the ongoing need for safer and more effective FXR-targeted treatments for liver fibrosis. Additionally, this review discusses the prospects of using OCA clinically for various liver diseases. The findings underscore the need for further research to optimize OCA therapy and address the complexities of managing liver fibrosis.