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
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Cyclosporine
KW - PBC
KW - Recurrence
KW - Survival
KW - Tacrolimus
KW - Transplantation
KW - UDCA
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U2 - 10.1016/j.jhep.2020.03.043
DO - 10.1016/j.jhep.2020.03.043
M3 - Article
C2 - 32275981
AN - SCOPUS:85086507927
VL - 73
SP - 559
EP - 565
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 3
ER -