Highlights
- •Preventive UDCA after liver transplantation for PBC is associated with a reduced risk of disease recurrence.
- •This parallels a reduction in the long-term risk of graft loss, liver-related death and all-cause death.
- •Exposure to cyclosporine rather than to tacrolimus added to the protective effect of UDCA.
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.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: April 07, 2020
Accepted:
March 23,
2020
Received in revised form:
March 6,
2020
Received:
December 19,
2019
Footnotes
Author names in bold designate shared co-first authorship
Identification
Copyright
© 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
