Obeticholic acid for the treatment of primary biliary cirrhosis

Expert Rev Clin Pharmacol. 2016;9(1):13-26. doi: 10.1586/17512433.2015.1092381. Epub 2015 Nov 7.


Primary biliary cirrhosis (PBC) is characterized by progressive nonsuppurative destruction of small bile ducts, resulting in intrahepatic cholestasis, fibrosis and ultimately end-stage liver disease. Timely intervention with ursodeoxycholic acid is associated with excellent survival, although approximately one-third of all patients fail to achieve biochemical response, signifying a critical need for additional therapeutic strategies. Obeticholic acid (OCA) is a potent ligand of the nuclear hormone receptor farnesoid X receptor (FXR). Activation of FXR inhibits bile acid synthesis and protects against toxic accumulation in models of cholestasis and facilitates hepatic regeneration in preclinical studies. Data from recent Phase II and III controlled trials suggest a therapeutic impact of OCA in PBC biochemical nonresponders, as evidenced by change in proven laboratory surrogates of long-term outcome. Dose-dependent pruritus is a common adverse effect, but may be overcome through dose-titration. Longer term studies are needed with focus on safety and long-term clinical efficacy.

Keywords: autoimmune disease; cholangitis; obeticholic acid; primary biliary cirrhosis; ursodeoxycholic acid.

Publication types

  • Review

MeSH terms

  • Animals
  • Chenodeoxycholic Acid / adverse effects
  • Chenodeoxycholic Acid / analogs & derivatives*
  • Chenodeoxycholic Acid / pharmacology
  • Chenodeoxycholic Acid / therapeutic use
  • Dose-Response Relationship, Drug
  • End Stage Liver Disease / etiology
  • End Stage Liver Disease / prevention & control
  • Humans
  • Liver Cirrhosis, Biliary / complications
  • Liver Cirrhosis, Biliary / drug therapy*
  • Pruritus / chemically induced
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Ursodeoxycholic Acid / therapeutic use


  • Receptors, Cytoplasmic and Nuclear
  • obeticholic acid
  • farnesoid X-activated receptor
  • Chenodeoxycholic Acid
  • Ursodeoxycholic Acid