Current and potential treatments for primary biliary cholangitis

Lancet Gastroenterol Hepatol. 2020 Mar;5(3):306-315. doi: 10.1016/S2468-1253(19)30343-7. Epub 2019 Dec 2.

Abstract

Up to 40% of patients with primary biliary cholangitis have an incomplete response to first-line treatment with ursodeoxycholic acid. Obeticholic acid was approved by the US Food and Drug Administration in 2016 as a second-line treatment for patients with primary biliary cholangitis who are unresponsive to ursodeoxycholic acid; however, approximately 50% of patients might need additional treatments to reach therapeutic goals. A considerable need exists for effective treatment options to prevent progression to liver transplantation or death in these patients. Drugs that might modulate immunological abnormalities in primary biliary cholangitis have been studied but their effectiveness varies. Budesonide, ciclosporin, and rituximab have shown potential in modifying the disease process. Bezafibrate, a pan-peroxisome proliferator-activated receptor agonist, has been shown to ameliorate deranged bile acid homoeostasis and attenuate raised concentrations of liver enzymes associated with primary biliary cholangitis. As the mechanisms underlying the pathogenesis and progression of primary biliary cholangitis are further clarified, specific targeted therapies are under development with promising early results. Various therapeutic target bile acid homeostasis, immune dysfunction, and fibrogenetic pathways are being studied. A better understanding of the biochemical and clinical effects of the therapies in development bear discussion, both to guide the discovery of new therapies and to inform clinicians so that rational treatment regimens can be tailored to patients once they become available.

Publication types

  • Review

MeSH terms

  • Benzothiazoles / pharmacology
  • Benzothiazoles / therapeutic use
  • Bezafibrate / pharmacology
  • Bezafibrate / therapeutic use
  • Bile Acids and Salts / physiology
  • Budesonide / pharmacology
  • Budesonide / therapeutic use
  • Case-Control Studies
  • Chenodeoxycholic Acid / analogs & derivatives
  • Chenodeoxycholic Acid / chemistry
  • Chenodeoxycholic Acid / pharmacology
  • Chenodeoxycholic Acid / therapeutic use
  • Cholagogues and Choleretics / chemistry
  • Cholagogues and Choleretics / pharmacology
  • Cholagogues and Choleretics / therapeutic use
  • Clinical Trials as Topic
  • Cyclosporine / pharmacology
  • Cyclosporine / therapeutic use
  • Disease Progression
  • Glucocorticoids / pharmacology
  • Glucocorticoids / therapeutic use
  • Homeostasis / drug effects*
  • Humans
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use
  • Isoxazoles / pharmacology
  • Isoxazoles / therapeutic use
  • Liver Cirrhosis, Biliary / complications*
  • Liver Cirrhosis, Biliary / drug therapy*
  • Liver Cirrhosis, Biliary / metabolism
  • Liver Cirrhosis, Biliary / physiopathology
  • Liver Transplantation / statistics & numerical data
  • Peroxisome Proliferator-Activated Receptors / agonists
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Rituximab / pharmacology
  • Rituximab / therapeutic use
  • Treatment Outcome
  • United States / epidemiology
  • United States Food and Drug Administration / organization & administration
  • Ursodeoxycholic Acid / chemistry
  • Ursodeoxycholic Acid / pharmacology
  • Ursodeoxycholic Acid / therapeutic use

Substances

  • Benzothiazoles
  • Bile Acids and Salts
  • Cholagogues and Choleretics
  • Glucocorticoids
  • Immunologic Factors
  • Immunosuppressive Agents
  • Isoxazoles
  • Peroxisome Proliferator-Activated Receptors
  • Receptors, Cytoplasmic and Nuclear
  • obeticholic acid
  • farnesoid X-activated receptor
  • Chenodeoxycholic Acid
  • Rituximab
  • Budesonide
  • Ursodeoxycholic Acid
  • Cyclosporine
  • tropifexor
  • Bezafibrate