Long-term impact of preventive UDCA therapy after transplantation for primary biliary cholangitis.
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.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.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.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.