Type of calcineurin inhibitor and long-term outcomes following liver transplantation in patients with Primary Biliary Cholangitis- an ELTR study

Background Tacrolimus has been associated with recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT), which in turn may reduce survival. This study aimed to assess the relation between the type of calcineurin inhibitor (CNI) and long-term outcomes following LT in patients with PBC. Methods Survival analyses were used to assess the association between immunosuppressive drugs and graft or patient survival among adult patients with PBC in the dataset of the European Liver Transplant Registry. Patients who received a donation after brain death (DBD) graft between 1990 and 2021 with at least one year of event-free follow-up were included. Results In total, 3175 PBC patients were followed for a median duration of 11.4 years (IQR 5.9 – 17.9) after LT. Tacrolimus (Tac) was registered in 2056 (64.8%) patients and cyclosporin (CsA) in 819 (25.8%). Adjusted for recipient age, recipient sex, donor age, and year of LT, Tac was not associated with higher risk of graft loss (aHR 1.07, 95%CI 0.92-1.25, p=0.402) or death (aHR 1.06, 95%CI 0.90-1.24, p=0.473) over CsA. In this model maintenance mycophenolate was associated with a lower risk of graft loss (aHR 0.72, 95%CI 0.60-0.87, p<0.001) or death (aHR 0.72, 95%CI 0.59-0.87, p<0.001), while these risks were higher with use of steroids (aHR 1.31, 95%CI 1.13-1.52, p<0.001, and aHR 1.34, 95%CI 1.15-1.56, p<0.001, respectively). Conclusions In this large LT registry, type of CNI was not associated with long-term graft or recipient survival, reassuring us to continue the use of Tac post LT in the population with PBC. Patients using MMF had a lower risk of graft loss and death, indicating that threshold for combination treatment with Tac and MMF should be low. Impact And Implications This study investigated the association between immunosuppressive drugs and the long-term survival of patients with primary biliary cholangitis (PBC) following DBD liver transplantation (LT). While tacrolimus has been previously related to a higher risk of PBC recurrence, the type of calcineurin inhibitor was not related to graft or patient survival among patient transplanted for PBC in the European Liver Transplant Registry. Additionally, maintenance use of mycophenolate was linked to lower risks of graft loss and death, while these risks were higher with maintenance use of steroids. Our findings reassure physicians on the continued use of Tac after LT in the population with PBC, and suggest potential benefit from combination therapy with mycophenolate.