Long-term impact of preventive UDCA therapy after transplantation for primary biliary cholangitis

Research output: Contribution to journalArticle

Authors

  • Global PBC Study Group

Colleges, School and Institutes

External organisations

  • Sorbonne University
  • Alberta Glycomics Centre, University of Alberta, Alberta, Canada
  • Charité University Hospital of Berlin
  • University Medical Center Hamburg-Eppendorf
  • University Teaching Hospital Adult Hospital
  • University Hospital Jena, Germany
  • Institute for Liver and Digestive Health, Division of Medicine, University College London and Royal Free Hospital, NHS Foundation Trust, London, UK.
  • The University of Toronto, Toronto, Canada
  • University Hospitals Birmingham National Health Service Foundation Trust, Birmingham, England.
  • University Hospitals of Coventry
  • UMR5558; CNRS and Lyon 1 Claude Bernard University; Lyon France
  • Division of Tropical and Humanitarian Medicine, University of Geneva and Geneva University Hospitals, Geneva, Switzerland.
  • ADEE Liaison University of Barcelona Barcelona Spain
  • Transplant Hepatology Unit
  • Padova University Hospital
  • Ghent University Hospital, Ghent, Belgium.
  • Erasmus University Medical Center

Abstract

BACKGROUND & AIMS: Recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT) is frequent and able to impair graft and patient survival. Ursodeoxycholic acid (UDCA) is the current standard therapy for PBC. We investigated the effect of preventive exposure to UDCA on the incidence and long-term consequences of PBC recurrence after LT.

METHODS: We did a retrospective cohort study including 780 patients transplanted for PBC from 1983 to 2017 in 16 centers and 9 countries and followed-up for a median time of 11 years. Among them, 190 received UDCA (10-15 mg/kg/d) preventively. The primary outcome was PBC recurrence as proven by histology. The secondary outcomes were graft loss, liver-related death, and all-cause death. The association between preventive UDCA and outcomes was quantified using multivariable-adjusted Cox and restricted mean survival time (RMST) models.

RESULTS: While recurrence of PBC significantly shortened graft and patient survivals, preventive exposure to UDCA was associated with reduced risk for PBC recurrence (adjusted hazard ratio, 0.41; 95%CI, 0.28 - 0.61; p<0.0001), graft loss (0.33; 0.13 - 0.82; p<0.05), liver-related death (0.46; 0.22 - 0.98; p<0.05), and all-cause death (0.69; 0.49 - 0.96; p<0.05). RMST analysis showed consistent results with a survival gain of 2.26 years (95%CI 1.28 - 3.25) over 20 years. Exposure to cyclosporine rather than to tacrolimus added to the preventive effect of UDCA against PBC recurrence and all-cause death.

CONCLUSIONS: Preventive UDCA after LT for PBC is associated with reduced risk for disease recurrence, graft loss, and death. Regimen combining cyclosporine and preventive UDCA is associated with the lowest risk of PBC recurrence and mortality.

Bibliographic note

Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Details

Original languageEnglish
JournalJournal of Hepatology
Early online date7 Apr 2020
Publication statusE-pub ahead of print - 7 Apr 2020

Keywords

  • PBC, UDCA, Transplantation, Cyclosporine, Tacrolimus, Recurrence, Survival