title: Fibrate treatment for primary biliary cirrhosis.
abstract: OBJECTIVE
  Primary biliary cirrhosis (PBC) can lead to end-stage liver disease and death. Ursodeoxycholic acid (UDCA) treatment can normalize serum liver enzymes in PBC, and such UDCA-responsive patients have a similar life expectancy as age and sex-matched controls. Nearly up to 50% of the patients with PBC, depending on sex and age at diagnosis, show an incomplete biochemical response to UDCA and require additional/alternative treatment. The purpose of this review is to critically evaluate the molecular mechanisms and clinical benefit of fibrate treatment in these patients.
  
  
  RESULTS
  Fibrates have anticholestatic, anti-inflammatory, and antifibrotic effects in animal and in-vitro studies. The mechanisms that underlie these effects are complementary, and largely mediated through activation of peroxisome proliferator activated receptors. Fibrate treatment ameliorated liver biochemical tests in UDCA unresponsive patients, either as mono-therapy or in combination with UDCA. These results, however, were obtained in case series and small pilot studies. The results of phase III studies, such as the Bezafibrate in Combination With Ursodeoxycholic Acid in Primary Biliary Cirrhosis (BEZURSO) trial, are currently awaited.
  
  
  CONCLUSIONS
  A considerable body of observational evidence supports the safety and efficacy of fibrate treatment in PBC patients with an incomplete response to UDCA. These results encourage the evaluation of its effects on liver-related morbidity and mortality in larger clinical trials.
authors.affiliation: Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Wien, Austria.
authors.forename: Frans J C
authors.initials: FJ
authors.lastname: Cuperus
authors.forename: Emina
authors.initials: E
authors.lastname: Halilbasic
authors.forename: Michael
authors.initials: M
authors.lastname: Trauner
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D058607:Fibric Acids / Q000627:therapeutic use*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy*; D017211:Treatment Failure; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D058607:Fibric Acids; D000960:Hypolipidemic Agents; D014580:Ursodeoxycholic Acid