title: Prolonged follow-up of patients in the U.S. multicenter trial of ursodeoxycholic acid for primary biliary cirrhosis.
abstract: OBJECTIVE
  Randomized, double-blind, placebo-controlled trials of ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis (PBC) have not demonstrated improvement in survival during the placebo-controlled phases of these trials. Analyses purporting to demonstrate a survival advantage of UDCA are largely dependent on data obtained after the placebo phases were terminated, and placebo-treated patients were offered open-label UDCA. After completion of our 2-yr placebo-controlled trial of UDCA in which we observed no survival benefit for UDCA, we provided the patients with open-label UDCA to see if delay in providing UDCA for 2 yr had any effect on subsequent liver transplantation or death without liver transplantation.
  
  
  METHODS
  In our previously reported 2-yr placebo-controlled trial, 151 patients with PBC were randomized to receive either UDCA (n = 77) or placebo (n = 74). The number of patients who progressed to liver transplantation or death without transplantation were similar in both the groups, 12 (16%) in the UDCA-treated and 11 (15%) in placebo-treated patients. All the patients were then offered open-label UDCA, with 61 original UDCA and 56 original placebo-treated patients now taking UDCA in an extended open-label phase of the trial.
  
  
  RESULTS
  No significant differences were observed in the number of patients who underwent liver transplantation or died without liver transplantation in the open-label phase of the trial. Moreover, no difference in the time to these endpoints was seen over the period of observation of as long as 6 yr from the time of initial randomization.
  
  
  CONCLUSIONS
  Results of open-label extensions of previous conducted placebo-controlled trials of UDCA in PBC leave uncertain whether UDCA impacts significantly on liver transplantation and death without liver transplantation in patients with PBC.
authors.affiliation: University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9151, USA.
authors.forename: Burton
authors.initials: B
authors.lastname: Combes
authors.forename: Velimir A
authors.initials: VA
authors.lastname: Luketic
authors.forename: Marion G
authors.initials: MG
authors.lastname: Peters
authors.forename: Rowen K
authors.initials: RK
authors.lastname: Zetterman
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Garcia-Tsao
authors.forename: Santiago J
authors.initials: SJ
authors.lastname: Munoz
authors.forename: Danyu
authors.initials: D
authors.lastname: Lin
authors.forename: Nancy
authors.initials: N
authors.lastname: Flye
authors.forename: Robert L
authors.initials: RL
authors.lastname: Carithers
mesh_terms: D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D016031:Liver Transplantation; D016019:Survival Analysis; D016896:Treatment Outcome; D014481:United States; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid