Advances in pharmacotherapy for primary biliary cirrhosis

Expert Opin Pharmacother. 2015 Apr;16(5):633-43. doi: 10.1517/14656566.2015.998650. Epub 2014 Dec 29.


Introduction: Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease mostly seen in middle-aged women characterized by progressive nonsuppurative destruction of small bile ducts resulting in intrahepatic cholestasis, parenchymal injury and ultimately end-stage liver disease. Despite major breakthroughs in our understanding of PBC, there remains only one FDA-approved agent for treatment: ursodeoxycholic acid (UDCA) to which one-third of patients are unresponsive.

Areas covered: Biochemical response to treatment with UDCA is associated with excellent survival rates in PBC patients. However, there is a need for alternative treatments for nonresponders. Results from human epidemiological and genetic studies as well as preclinical studies in PBC animal models have provided a strong impetus for the development of new therapeutic agents. In this review, we discuss the recent advances in translational research in PBC focusing on promising therapeutic approaches, namely immune-based targeted therapies and agents targeting the synthesis and circulation of bile acids.

Expert opinion: We are in a new era for the development of novel therapies for PBC. Data on fibrates, budesonide and obeticholic acid offer encouragement for nonresponders to UDCA.

Trial registration: NCT00746486 NCT01389973 NCT01430429 NCT01473524.

Keywords: biologics; farnesoid X receptor agonists; primary biliary cirrhosis; ursodeoxycholic acid.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / pathology
  • Bile Acids and Salts / metabolism
  • Budesonide / therapeutic use
  • Chenodeoxycholic Acid / analogs & derivatives
  • Chenodeoxycholic Acid / therapeutic use
  • End Stage Liver Disease / prevention & control
  • Female
  • Fibric Acids / therapeutic use
  • Humans
  • Liver / metabolism
  • Liver Cirrhosis, Biliary / drug therapy*
  • Liver Cirrhosis, Biliary / pathology
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Signal Transduction
  • Treatment Failure
  • Ursodeoxycholic Acid / therapeutic use


  • Bile Acids and Salts
  • Fibric Acids
  • Receptors, Cytoplasmic and Nuclear
  • obeticholic acid
  • Chenodeoxycholic Acid
  • Budesonide
  • Ursodeoxycholic Acid

Associated data