Advances in pharmacotherapy for primary biliary cirrhosis

Abstract

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.

Keywords:

• biologics
• farnesoid X receptor agonists
• primary biliary cirrhosis
• ursodeoxycholic acid

Declaration of interest

The contribution represents original work that has not been previously published or simultaneously submitted for publication elsewhere. The manuscript has been read and approved by all the authors, and all the conditions as previously stated by the ICMJE have been met. The body providing explicit ethical approval of the work reported is stated. Supported in part by National Institutes of Health grant DK39588. The authors’ preference for publication is US spellings. The authors have enrolled patients in some cited trials (NCT01473524, NCT00746486, NCT01389973, NCT01430429).

Notes

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