title: A randomized controlled trial of high-dose ursodesoxycholic acid for nonalcoholic steatohepatitis.
abstract: OBJECTIVE
  Nonalcoholic steatohepatitis (NASH) is a prevalent liver disease associated with increased morbidity and mortality. Ursodeoxycholic acid (UDCA) may have antioxidant, anti-inflammatory, and antifibrotic properties and may reduce liver injury in NASH. To date, no studies have assessed the efficacy and safety of high-dose UDCA (HD-UDCA) in patients with NASH.
  
  
  METHODS
  We conducted a 12-month, randomized, double-blind, placebo-controlled multicenter trial to evaluate the efficacy and safety of HD-UDCA (28-35 mg/kg per day) in 126 patients with biopsy-proven NASH and elevated alanine aminotransferase (ALT) levels. The primary study end point was reduction in ALT levels from baseline in patients treated with HD-UDCA compared with placebo. Secondary study end points were the proportion of patients with ALT normalization, relative reduction in the scores of serum markers of fibrosis and hepatic inflammation, and safety and tolerability.
  
  
  RESULTS
  HD-UDCA significantly reduced mean ALT levels -28.3% from baseline after 12 months compared with -1.6% with placebo (p<0.001). At the end of the trial, ALT levels normalized (≤35 IU/L) in 24.5% of patients treated with HD-UDCA and in 4.8% of patients who received placebo (p=0.003). Both results were not accounted for by changes in weight during the trial. HD-UDCA significantly reduced the FibroTest® serum fibrosis marker (p<0.001) compared with placebo. HD-UDCA also significantly improved markers of glycemic control and insulin resistance. There were no safety issues in this population.
  
  
  CONCLUSIONS
  Treatment with HD-UDCA was safe, improved aminotransferase levels, serum fibrosis markers, and selected metabolic parameters. Studies with histologic end points are warranted.
authors.affiliation: Université Pierre et Marie Curie, Assistance Publique - Hôpitaux de Paris, Hôpital Pitié Salpêtrière, Inserm UMR_S 938, Paris, France. vratziu@teaser.fr
authors.forename: Vlad
authors.initials: V
authors.lastname: Ratziu
authors.forename: Victor
authors.initials: V
authors.lastname: de Ledinghen
authors.forename: Fréderic
authors.initials: F
authors.lastname: Oberti
authors.forename: Philippe
authors.initials: P
authors.lastname: Mathurin
authors.forename: Claire
authors.initials: C
authors.lastname: Wartelle-Bladou
authors.forename: Christophe
authors.initials: C
authors.lastname: Renou
authors.forename: Philippe
authors.initials: P
authors.lastname: Sogni
authors.forename: Marianne
authors.initials: M
authors.lastname: Maynard
authors.forename: Dominique
authors.initials: D
authors.lastname: Larrey
authors.forename: Lawrence
authors.initials: L
authors.lastname: Serfaty
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnefont-Rousselot
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Bastard
authors.forename: Marc
authors.initials: M
authors.lastname: Rivière
authors.forename: Jean
authors.initials: J
authors.lastname: Spénard
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D002756:Cholagogues and Choleretics / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005234:Fatty Liver / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D001786:Blood Glucose; D002756:Cholagogues and Choleretics; D006442:Glycated Hemoglobin; D007328:Insulin; D014580:Ursodeoxycholic Acid; C517652:hemoglobin A1c protein, human