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

Global PBC Study Group, Christophe Corpechot, Olivier Chazouillères, Pierre Belnou, Aldo J. Montano-Loza, Andrew Mason, Maryam Ebadi, Dennis Eurich, Sascha Chopra, Dietmar Jacob, Christoph Schramm, Martina Sterneck, Tony Bruns, Philipp Reuken, Falk Rauchfuss, Davide Roccarina, Douglas Thorburn, Alessio Gerussi, Palak Trivedi, Gideon HirschfieldPatrick McDowell, Frederik Nevens, Olivier Boillot, Alexie Bosch, Emiliano Giostra, Filomena Conti, Raoul Poupon, Albert Parés, Anna Reig, Maria Francesca Donato, Federica Malinverno, Annarosa Floreani, Francesco Paolo Russo, Nora Cazzagon, Xavier Verhelst, Jorn Goet, Maren Harms, Henk van Buuren, Bettina Hansen, Fabrice Carrat, Jérôme Dumortier

Research output: Contribution to journalArticlepeer-review

Abstract

Background & Aims: Recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT) is frequent and can 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 performed a retrospective cohort study in 780 patients transplanted for PBC, between 1983–2017 in 16 centers (9 countries), and followed-up for a median of 11 years. Among them, 190 received preventive UDCA (10–15 mg/kg/day). The primary outcome was histological evidence of PBC recurrence. 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 survival, preventive exposure to UDCA was associated with reduced risk of PBC recurrence (adjusted hazard ratio [aHR] 0.41; 95% CI 0.28–0.61; p <0.0001), graft loss (aHR 0.33; 95% CI 0.13–0.82; p <0.05), liver-related death (aHR 0.46; 95% CI 0.22–0.98; p <0.05), and all-cause death (aHR 0.69; 95% CI 0.49–0.96; p <0.05). On RMST analysis, preventive UDCA led to a survival gain of 2.26 years (95% CI 1.28–3.25) over a period of 20 years. Exposure to cyclosporine rather than tacrolimus had a complementary protective effect alongside preventive UDCA, reducing the cumulative incidence of PBC recurrence and all-cause death. Conclusions: Preventive UDCA after LT for PBC is associated with a reduced risk of disease recurrence, graft loss, and death. A regimen combining cyclosporine and preventive UDCA is associated with the lowest risk of PBC recurrence and mortality. Lay summary: Recurrence of primary biliary cholangitis after liver transplantation is frequent and can impair graft and patient survival. We performed the largest international study of transplanted patients with primary biliary cholangitis to date. Preventive administration of ursodeoxycholic acid after liver transplantation was associated with reduced risk of disease recurrence, graft loss, liver-related and all-cause mortality. A regimen combining cyclosporine and preventive ursodeoxycholic acid was associated with the best outcomes.

Original languageEnglish
Pages (from-to)559-565
JournalJournal of Hepatology
Volume73
Issue number3
DOIs
Publication statusPublished - 2020

Keywords

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

ASJC Scopus subject areas

  • Hepatology

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