Factors Associated With Recurrence of Primary Biliary Cholangitis After Liver Transplantation and Effects on Graft and Patient Survival

Abstract

Primary biliary cholangitis (PBC) frequently recurs after liver transplantation. We evaluated riskfactors associated with recurrence of PBC and its effects onpatient and graft survival in a multicenter, international cohort (the Global PBC Study Group). 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 frombiochemical 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 amedian 6.9 years (interquartile range, 6.1-7.9 years). 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 PBCrecurrence, 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). 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.