The Nordic multicenter double-blind randomized controlled trial of prophylactic ursodeoxycholic acid in liver transplant patients

Transplantation. 1997 Jun 15;63(11):1591-4. doi: 10.1097/00007890-199706150-00009.

Abstract

Background: Prophylactic treatment with ursodeoxycholic acid (UDCA) has been reported to reduce the incidence of acute rejection after liver transplantation compared with historical controls. We investigated this in a prospective, randomized, placebo-controlled multicenter study.

Methods: Fifty-four liver transplant patients were allocated to the UDCA treatment group (15 mg/kg/day), and 48 patients were allocated to the placebo group. Trial medicine was started on the first postoperative day and was given for 3 months. Follow-up was for 12 months. Treatment was stratified for adults with chronic liver disease (n=77), adults with acute liver failure (n=10), and children (n=15).

Results: The frequency of patients with acute rejection was 65% in the UDCA treatment group and 68% in the placebo group. The frequency of steroid-resistant rejection was similar in both groups. The probability of acute rejection, analyzed according to the intention-to-treat policy with Kaplan-Meier analysis, was similar in both treatment groups. No significant differences were found in patient survival and graft survival probabilities. For the biochemical markers of cholestasis, only gamma-glutamyltransferase was significantly improved after 2 months of UDCA treatment.

Conclusions: The initial optimistic report of a beneficial effect of prophylactic treatment with UDCA on acute rejection after liver transplantation was not confirmed in this controlled study.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alanine Transaminase / blood
  • Alkaline Phosphatase / blood
  • Bilirubin / blood
  • Child
  • Child, Preschool
  • Cyclosporine / blood
  • Double-Blind Method
  • Female
  • Graft Rejection / prevention & control
  • Graft Survival / drug effects
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Infant
  • Liver Transplantation / immunology*
  • Male
  • Middle Aged
  • Time Factors
  • Ursodeoxycholic Acid / therapeutic use*
  • gamma-Glutamyltransferase / blood

Substances

  • Immunosuppressive Agents
  • Ursodeoxycholic Acid
  • Cyclosporine
  • gamma-Glutamyltransferase
  • Alanine Transaminase
  • Alkaline Phosphatase
  • Bilirubin