Emerging drugs for the treatment of non-alcoholic steatohepatitis: a focused review of farnesoid X receptor agonists

ABSTRACT

Introduction

The discovery of the farnesoid X receptor and its role in bile and lipid homeostasis has led to the investigation of FXR agonists as a therapy in cholestatic disorders and in NAFLD. With increasing prevalence of obesity and metabolic syndrome, NAFLD has grown to become the most prevalent chronic liver disease, present in a quarter of the worldwide population. FXR agonists represent a promising avenue for this burgeoning disease with few options for pharmacologic therapy.

Areas covered

A brief overview of the epidemiology of NAFLD/NASH and a review of current evidence on available treatments is provided. For FXR agonists, a review is performed of mechanisms of action, efficacy, and adverse effects. Finally, hurdles to widespread adoption of this drug class in treatment of NASH are described. Prospective clinical trials were reviewed on the US National Library of Medicine database at clinicaltrials.gov, along with a literature search of meta-analyses, reviews, and original research.

Expert opinion

FXR agonists show promise for treating NASH with positive effects on several surrogate markers of disease including liver fibrosis on biopsy, fat reduction on MRI, and decrease in liver enzymes. However, their long-term tolerability, safety, and efficacy on liver-related outcomes need to be established.

KEYWORDS:

• Farnesoid x receptor
• obeticholic acid
• NAFLD
• NASH

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

KV Kowdley received research support from Intercept, Gilead Sciences, Novartis, Glaxo Smith Kline, Genfit and Enata; serves as a consultant and speaker for Gilead Sciences and Intercept. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.