Incomplete response to ursodeoxycholic acid in primary biliary cholangitis: criteria, epidemiology, and possible mechanisms

Expert Rev Gastroenterol Hepatol. 2022 Nov-Dec;16(11-12):1065-1078. doi: 10.1080/17474124.2022.2153672. Epub 2022 Dec 5.

Abstract

Introduction: As a common autoimmune disease with the characteristic of early complication, primary biliary cholangitis (PBC) leads to an increasing number of mortalities among people with end-stage liver disease (ESLD) waiting for liver transplantation. Ursodeoxycholic acid (UDCA) is the only approved first-line medicine for PBC, and a good response to treatment could acquire an ideal prognosis. Patients with poor UDCA response usually have more adverse outcomes and worse survival, therefore, the management of this group become a major consideration.

Areas covered: Due to the complexity of race and environment for PBC, different criteria for UDCA response exhibit various predictive performances. Factors affecting UDCA response conditions include gender, age, ethnicity, serum indicators, auto-antibodies, and autoimmune comorbidities, while no agreement has been reached. In this review, we mainly focus on cellular senescence, immune-mediated damage, and vitamin D deficiency as possible mechanisms for UDCA non-responders.

Expert opinion: The pathogenesis of PBC has yet to be clarified. Immunology-related mechanisms and therapy targets ought to be the main effort made for further study. Irrespective of the response condition, UDCA is recommended for routine administration in all PBC patients without contraindication. Ongoing clinical trials of second-line and additional therapy exhibit promising prospects.

Keywords: Mechanisms; predicting factors; primary biliary cholangitis; response; ursodeoxycholic acid.

Publication types

  • Review

MeSH terms

  • Cholagogues and Choleretics / adverse effects
  • Cholangitis* / drug therapy
  • Humans
  • Liver Cirrhosis, Biliary* / diagnosis
  • Liver Cirrhosis, Biliary* / drug therapy
  • Liver Cirrhosis, Biliary* / epidemiology
  • Prognosis
  • Ursodeoxycholic Acid / adverse effects

Substances

  • Ursodeoxycholic Acid
  • Cholagogues and Choleretics