Treatment of Nonalcoholic Steatohepatitis by Obeticholic Acid: Current Status

Nonalcoholic fatty liver disease (NAFLD) is one of the major and prevalent liver diseases from the national and global perspectives. It appears that considerable numbers of the general population have been suffering from NAFLD. When a patient with NAFLD also exhibits inflammation of the liver, the condition is regarded as nonalcoholic steatohepatitis (NASH). Nonalcoholic steatohepatitis is a pathological entity that may progress to cirrhosis of the liver (LC) and hepatocellular carcinoma (HCC). It is acceptable by all that the health burden of NAFLD and NASH is tremendous. Due to the increased prevalence of these pathologies, extensive research has been conducted regarding pathogenesis, diagnostic tools, and staging of the diseases. However, adequate and approved pharmacotherapy for these pathologies is lacking. The farnesoid receptor (FXR) is a bile acid-activated receptor. It regulates lipid, glucose, bile acid metabolism. Farnesoid receptor is also endowed with anti-inflammatory and anti-fibrotic properties on the liver. Obeticholic acid (OCA), a potent and selective FXR ligand, may become a promising molecule to combat NASH and advanced fibrosis. The present review briefly discusses the current recommendation of NASH management with available pharmacological treatments. The scope of OCA with a focus on recent data of major randomized controlled trials (RCTs) is discussed. On the basis of current data and recent interim analysis, OCA seems to improve insulin resistance, steatohepatitis, levels of alanine transaminase (ALT) and fibrosis in NASH. Dose-related adverse effects like pruritus and dyslipidemia may limit its usage. Also, its usage may be restricted in patients with NASH cirrhosis. More adequately powered RCTs that would contain NASH patients with different and heterogeneous properties would be required to develop consensus about these issues. The safety profile of different doses of OCA needs to be established in these patients as well as there remain considerable queries about these.

Roy PP, Mahtab MA, Rahim MA, et al. Treatment of Nonalcoholic Steatohepatitis by Obeticholic Acid: Current Status. Euroasian J Hepato-Gastroenterol 2022;12(Suppl 1):S46-S50.