Editorial
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2016; 22(41): 9039-9043
Published online Nov 7, 2016. doi: 10.3748/wjg.v22.i41.9039
Emerging role of obeticholic acid in the management of nonalcoholic fatty liver disease
Evangelia Makri, Evangelos Cholongitas, Konstantinos Tziomalos
Evangelia Makri, Konstantinos Tziomalos, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 54636 Thessaloniki, Greece
Evangelos Cholongitas, Fourth Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, 54642 Thessaloniki, Greece
Author contributions: Makri E drafted the editorial; Cholongitas E and Tziomalos K critically revised the draft.
Conflict-of-interest statement: All authors declare no conflict of interest related to this publication.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Evangelos Cholongitas, MD, PhD, Assistant Professor of Internal Medicine, Fourth Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, 49 Konstantinoupoleos street, 54642 Thessaloniki, Greece. cholongitas@yahoo.gr
Telephone: +30-6936-378903 Fax: +30-2310-992940
Received: July 18, 2016
Peer-review started: July 21, 2016
First decision: August 29, 2016
Revised: August 31, 2016
Accepted: September 28, 2016
Article in press: September 28, 2016
Published online: November 7, 2016
Processing time: 111 Days and 13.9 Hours
Abstract

Nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease and its prevalence is increasing driven by the pandemic of obesity and type 2 diabetes mellitus. NAFLD can progress to cirrhosis and is associated with increased risk for cardiovascular disease and hepatocellular cancer. Diet and exercise are limited by suboptimal long-term adherence in patients with NAFLD. On the other hand, current pharmacological treatment of NAFLD has limited efficacy and unfavorable safety profile. In this context, obeticholic acid (OCA), a selective agonist of the farnesoid X receptors, might represent a useful option in these patients. Preclinical studies suggest that OCA improves hepatic steatosis, inflammation and fibrosis. A proof-of-concept study and the randomized, placebo-controlled Farnesoid X Receptor Ligand Obeticholic Acid in non-alcoholic steatohepatitis Treatment (FLINT) trial also showed improvements in liver histology in patients with NAFLD who received OCA. Weight loss and reduction in blood pressure were also observed. However, the effects of OCA on insulin resistance are conflicting and the lipid profile is adversely affected by this agent. In addition, pruritus is frequently observed during treatment with OCA and might lead to treatment discontinuation. However, given the limitations of existing treatments for NAFLD, OCA might represent a useful therapeutic option in selected patients with NAFLD.

Keywords: Nonalcoholic fatty liver disease; Obeticholic acid; Farnesoid X receptors; Insulin resistance; Fibrosis; Dyslipidemia; Steatosis; Hepatocellular cancer

Core tip: Nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease in Western countries, can progress to cirrhosis and is associated with increased all-cause and cardiovascular disease mortality risk. Current pharmacological treatment of NAFLD has limited efficacy and therefore, there is a pressing need to develop more effective and safe agents for this common and life-threatening disease. Obeticholic acid (OCA), a selective agonist of the farnesoid X receptors, might be a useful agent in the management of NAFLD. In the Farnesoid X Receptor Ligand Obeticholic Acid in non-alcoholic steatohepatitis (NASH) Treatment (FLINT) trial in patients with NASH, OCA administration was associated with improvements in liver histology, while weight loss and reduction in blood pressure were also observed. Although its adverse effects on the lipid profile and insulin sensitivity are worrisome, given the increased cardiovascular risk of this population, OCA might be considered in selected patients with NAFLD/NASH, particularly in those with adequately controlled glucose and lipid levels.