TY - JOUR
T1 - Long-term impact of preventive UDCA therapy after transplantation for primary biliary cholangitis
AU - Global PBC Study Group
AU - Corpechot, Christophe
AU - Chazouillères, Olivier
AU - Belnou, Pierre
AU - Montano-Loza, Aldo J
AU - Mason, Andrew
AU - Ebadi, Maryam
AU - Eurich, Dennis
AU - Chopra, Sascha
AU - Jacob, Dietmar
AU - Schramm, Christoph
AU - Sterneck, Martina
AU - Bruns, Tony
AU - Reuken, Philipp
AU - Rauchfuss, Falk
AU - Roccarina, Davide
AU - Thorburn, Douglas
AU - Gerussi, Alessio
AU - Trivedi, Palak
AU - Hirschfield, Gideon
AU - McDowell, Patrick
AU - Nevens, Frederik
AU - Boillot, Olivier
AU - Bosch, Alexie
AU - Giostra, Emiliano
AU - Conti, Filomena
AU - Poupon, Raoul
AU - Parés, Albert
AU - Reig, Anna
AU - Donato, Maria Francesca
AU - Malinverno, Federica
AU - Floreani, Annarosa
AU - Russo, Francesco Paolo
AU - Cazzagon, Nora
AU - Verhelst, Xavier
AU - Goet, Jorn
AU - Harms, Maren
AU - van Buuren, Henk
AU - Hansen, Bettina
AU - Carrat, Fabrice
AU - Dumortier, Jérôme
N1 - Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
PY - 2020/4/7
Y1 - 2020/4/7
N2 - 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.
AB - 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.
KW - Cyclosporine
KW - PBC
KW - Recurrence
KW - Survival
KW - Tacrolimus
KW - Transplantation
KW - UDCA
UR - http://www.scopus.com/inward/record.url?scp=85086507927&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2020.03.043
DO - 10.1016/j.jhep.2020.03.043
M3 - Article
C2 - 32275981
SN - 0168-8278
VL - 73
SP - 559
EP - 565
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 3
ER -