Bezafibrate normalizes alkaline phosphatase in primary biliary cirrhosis patients with incomplete response to ursodeoxycholic acid

Liver Int. 2014 Feb;34(2):197-203. doi: 10.1111/liv.12290. Epub 2013 Sep 2.

Abstract

Background & aims: Ursodeoxycholic acid (UDCA) is the standard treatment for primary biliary cirrhosis (PBC) but excellent response is not observed in all cases. Since potential favourable effects of fibrates have been reported in short series with inconclusive results, we have carried out a pilot study to analyse the effects of bezafibrate in patients with suboptimal response to UDCA.

Methods: Thirty women (age 52.3 ± 2.3 years) treated with UDCA and abnormal alkaline phosphatase (AP) levels received bezafibrate (400 mg/d) for 1 year. Changes were measured every 3 months during the study period of 12 months, 3 months after discontinuation and 3 months after resuming bezafibrate.

Results: Two patients discontinued the treatment after few days, three at 6 and one at 9 months. Bezafibrate treatment resulted in a significant decrease in AP as early as 3 months. Normalization or decrease of AP below 1.5 times normal levels was observed in 13 and 4 patients respectively. There was also a significant decrease in γ-glutamyl transferase and alanine aminotransferase, cholesterol and triglyceride levels. Bezafibrate treatment resulted in significant improvement of pruritus. A rebound in liver biochemistries and pruritus occurred upon drug discontinuation, changes which improved again after resuming bezafibrate. Response to bezafibrate was associated with lower liver stiffness and severity of cholestasis. No severe adverse effects were observed.

Conclusions: Combination treatment of bezafibrate and UDCA is associated with marked decrease or normalization of alkaline phosphatase as early as 3 months in patients with PBC. Better biochemical response was observed in patients with early disease and lower cholestasis.

Keywords: (PPARα) agonist; chronic cholestasis; liver stiffness; primary biliary cirrhosis; ursodeoxycholic acid therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism*
  • Bezafibrate / pharmacology*
  • Bezafibrate / therapeutic use
  • Elasticity Imaging Techniques
  • Female
  • Humans
  • Liver Cirrhosis, Biliary / drug therapy*
  • Liver Cirrhosis, Biliary / enzymology
  • Middle Aged
  • Pilot Projects
  • Prospective Studies
  • Statistics, Nonparametric
  • Treatment Outcome
  • Ursodeoxycholic Acid / therapeutic use

Substances

  • Ursodeoxycholic Acid
  • Alkaline Phosphatase
  • Bezafibrate