TY - JOUR
T1 - Factors associated with recurrence of primary biliary cholangitis after liver transplantation and effects on graft and patient survival
AU - Global PBC Study Group
AU - Montano-Loza, Aldo J
AU - Hansen, Bettina E
AU - Corpechot, Christophe
AU - Roccarina, Davide
AU - Thorburn, Douglas
AU - Trivedi, Palak
AU - Hirschfield, Gideon
AU - McDowell, Patrick
AU - Poupon, Raoul
AU - Dumortier, Jerome
AU - Bosch, Alexie
AU - Giostria, Emiliano
AU - Conti, Filomena
AU - Parés, Albert
AU - Reig, Anna
AU - Floreani, Annarosa
AU - Russo, Francesco Paolo
AU - Goet, Jorn C
AU - Harms, Maren H
AU - van Buuren, Henk
AU - Van den Ende, Natalie
AU - Nevens, Frederik
AU - Verhelst, Xavier
AU - Donato, Maria Francesca
AU - Malinverno, Federica
AU - Ebadi, Maryam
AU - Mason, Andrew L
N1 - Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.
PY - 2019/1
Y1 - 2019/1
N2 - BACKGROUND & AIMS: Primary biliary cholangitis (PBC) frequently recurs after liver transplantation. We evaluated risk factors associated with recurrence of PBC and its effects on patient and graft survival in a multicenter, international cohort (the Global PBC Study Group).METHODS: We collected demographic and clinical data from 785 patients (89% female) with PBC who underwent liver transplantation (mean age, 54 ± 9 years) from February 1983 through June 2016, among 13 centers in North America and Europe. Results from biochemical tests performed within 12 months of liver transplantation were analyzed to determine whether markers of cholestasis could identify patients with recurrence of PBC (based on histologic analysis). Patients were followed for a median 6.9 years (interquartile range, 6.1-7.9 years).RESULTS: PBC recurred in 22% of patients after 5 years and 36% after 10 years. Age at diagnosis <50 years (hazard ratio [HR], 1.79; 95% CI, 1.36-2.36; P < .001), age at liver transplantation <60 years (HR, 1.39; 95% CI, 1.02-1.90; P = .04), use of tacrolimus (HR, 2.31; 95% CI, 1.72-3.10; P < .001), and biochemical markers of severe cholestasis (bilirubin ≥100 μmol or alkaline phosphatase >3-fold the upper limit of normal) at 6 months after liver transplantation (HR, 1.79; 95% CI, 1.16-2.76; P = .008) were associated with higher risk of PBC recurrence, whereas use of cyclosporine reduced risk of PBC recurrence (HR, 0.62; 95% CI, 0.46-0.82; P = .001). In multivariable Cox regression with time-dependent covariate, recurrence of PBC significantly associated with graft loss (HR, 2.01; 95% CI, 1.16-3.51; P = .01) and death (HR, 1.72; 95% CI, 1.11-2.65; P = .02).CONCLUSIONS: Younger age at the time of diagnosis with PBC or at liver transplantation, tacrolimus use, and biochemical markers of cholestasis after liver transplantation are associated with PBC recurrence. PBC recurrence reduces odds of graft and patient survival. Strategies are needed to prevent PBC recurrence or reduce its negative effects.
AB - BACKGROUND & AIMS: Primary biliary cholangitis (PBC) frequently recurs after liver transplantation. We evaluated risk factors associated with recurrence of PBC and its effects on patient and graft survival in a multicenter, international cohort (the Global PBC Study Group).METHODS: We collected demographic and clinical data from 785 patients (89% female) with PBC who underwent liver transplantation (mean age, 54 ± 9 years) from February 1983 through June 2016, among 13 centers in North America and Europe. Results from biochemical tests performed within 12 months of liver transplantation were analyzed to determine whether markers of cholestasis could identify patients with recurrence of PBC (based on histologic analysis). Patients were followed for a median 6.9 years (interquartile range, 6.1-7.9 years).RESULTS: PBC recurred in 22% of patients after 5 years and 36% after 10 years. Age at diagnosis <50 years (hazard ratio [HR], 1.79; 95% CI, 1.36-2.36; P < .001), age at liver transplantation <60 years (HR, 1.39; 95% CI, 1.02-1.90; P = .04), use of tacrolimus (HR, 2.31; 95% CI, 1.72-3.10; P < .001), and biochemical markers of severe cholestasis (bilirubin ≥100 μmol or alkaline phosphatase >3-fold the upper limit of normal) at 6 months after liver transplantation (HR, 1.79; 95% CI, 1.16-2.76; P = .008) were associated with higher risk of PBC recurrence, whereas use of cyclosporine reduced risk of PBC recurrence (HR, 0.62; 95% CI, 0.46-0.82; P = .001). In multivariable Cox regression with time-dependent covariate, recurrence of PBC significantly associated with graft loss (HR, 2.01; 95% CI, 1.16-3.51; P = .01) and death (HR, 1.72; 95% CI, 1.11-2.65; P = .02).CONCLUSIONS: Younger age at the time of diagnosis with PBC or at liver transplantation, tacrolimus use, and biochemical markers of cholestasis after liver transplantation are associated with PBC recurrence. PBC recurrence reduces odds of graft and patient survival. Strategies are needed to prevent PBC recurrence or reduce its negative effects.
KW - Age of Onset
KW - Biomarkers/blood
KW - Biopsy
KW - Europe
KW - Female
KW - Graft Survival
KW - Humans
KW - Immunosuppressive Agents/adverse effects
KW - Liver Cirrhosis, Biliary/blood
KW - Liver Transplantation/adverse effects
KW - Male
KW - Middle Aged
KW - North America
KW - Recurrence
KW - Risk Factors
KW - Tacrolimus/adverse effects
KW - Time Factors
KW - Treatment Outcome
U2 - 10.1053/j.gastro.2018.10.001
DO - 10.1053/j.gastro.2018.10.001
M3 - Article
C2 - 30296431
SN - 0016-5085
VL - 156
SP - 96-107.e1
JO - Gastroenterology
JF - Gastroenterology
IS - 1
ER -