Preventive Administration of Ursodeoxycholic Acid after Liver Transplantation for Primary Biliary Cholangitis Prevents Disease Recurrence and Prolongs Graft Survival
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 859 patients transplanted for PBC from 1983 to 2017 in 16 centers and 9 countries and followed-up for a median time of 10 years. Among them, 204 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 proportional-hazards models.ResultsWhile 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, 0.29 – 0.60; p<0.0001), graft loss (0.43; 0.20 – 0.92; p<0.05), and liver-related death (0.45; 0.21 – 0.96; p<0.05), but not all-cause death (0.85; 0.62 – 1.17). The survival gains without PBC recurrence, graft loss, or liver-related death associated with preventive UDCA were 1.43 years (95%CI, 0.82 – 2.03; p<0.0001) at 12 years and 3.40 years (2.18 – 4.62; p<0.0001) at 20 years. Exposure to cyclosporine rather than to tacrolimus added to the preventive effect of UDCA against PBC recurrence (p<0.0001).ConclusionsPreventive exposure to UDCA after LT for PBC is associated with reduced risk for PBC recurrence, graft loss, and liver-related death. Regimen combining cyclosporine, as opposed to tacrolimus, and preventive UDCA is associated with the lowest risk of PBC recurrence.
Keywords
primary biliary cholangitis transplantation ursodeoxycholic acid disease recurrence survival mortality chemoprevention Christophe Corpechot
M.D. (Conceptualization Formal analysis Investigation Methodology Supervision Validation Visualization Writing -original draft Writingreview & editing) Olivier Chazouillères
M.D. (Investigation Supervision Validation Writing -review & editing) Pierre Belnou (Data curation Formal analysis Investigation Methodology Writingreview & editing) Aldo J Montano-Loza
M.D.
Ph.D. (Investigation) Andrew L Mason
Ph.D. (Investigation) Maryam Ebadi
Ph.D. (Investigation)
primary biliary cholangitis
transplantation
ursodeoxycholic acid
disease recurrence
survival
mortality
chemoprevention Christophe Corpechot
M.D. (Conceptualization
Formal analysis
Investigation
Methodology
Supervision
Validation
Visualization
Writing -original draft
Writingreview & editing) Olivier Chazouillères
M.D. (Investigation
Writing -review & editing) Pierre Belnou (Data curation
Writingreview & editing) Aldo J Montano-Loza
| Origin | Files produced by the author(s) |
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