Type of calcineurin inhibitor and long-term outcomes following liver transplantation in patients with primary biliary cholangitis – an ELTR study

Background &amp; Aims: 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 association between the type of calcineurin inhibitor used 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 European Liver Transplant Registry. Patients who received a donation after brain death graft between 1990 and 2021 with at least 1 year of event-free follow-up were included. Results: In total, 3,175 patients with PBC were followed for a median duration of 11.4 years (IQR 5.9–17.9) after LT. Tacrolimus (Tac) was registered in 2,056 (64.8%) and cyclosporin in 819 (25.8%) patients. Following adjustment for recipient age, recipient sex, donor age, and year of LT, Tac was not associated with higher risk of graft loss (adjusted hazard ratio [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 cyclosporin. In this model, maintenance mycophenolate mofetil (MMF) was associated with a lower risk of graft loss (aHR 0.72, 95% CI 0.60-0.87, p &lt;0.001) or death (aHR 0.72, 95% CI 0.59-0.87, p &lt;0.001), while these risks were higher with use of steroids (aHR 1.31, 95% CI 1.13-1.52, p &lt;0.001, and aHR 1.34, 95% CI 1.15-1.56, p &lt;0.001, respectively). Conclusions: In this large LT registry, type of calcineurin inhibitor was not associated with long-term graft or recipient survival, providing reassurance regarding 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 the 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 donation after brain death liver transplantation. While tacrolimus has previously been related to a higher risk of PBC recurrence, the type of calcineurin inhibitor was not related to graft or patient survival among patients 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 should provide reassurance for physicians regarding the continued use of Tac after liver transplantation in the population with PBC, and suggest potential benefit from combination therapy with mycophenolate.</p

Recurrence of primary sclerosing cholangitis after liver transplantation – analysing the European Liver Transplant Registry and beyond

Liver transplantation for primary sclerosing cholangitis (PSC) can be complicated by recurrence of PSC (rPSC). This may compromise graft survival but the effect on patient survival is less clear. We investigated the effect of post-transplant rPSC on graft and patient survival in a large European cohort. Registry data from the European Liver Transplant Registry regarding all first transplants for PSC between 1980 and 2015 were supplemented with detailed data on rPSC from 48 out of 138 contributing transplant centres, involving 1,549 patients. Bayesian proportional hazards models were used to investigate the impact of rPSC and other covariates on patient and graft survival. Recurrence of PSC was diagnosed in 259 patients (16.7%) after a median follow-up of 5.0 years (quantile 2.5%-97.5%: 0.4–18.5), with a significant negative impact on both graft (HR 6.7; 95% CI 4.9–9.1) and patient survival (HR 2.3; 95% CI 1.5–3.3). Patients with rPSC underwent significantly more re-transplants than those without rPSC (OR 3.6, 95% CI 2.7–4.8). PSC recurrence has a negative impact on both graft and patient survival, independent of transplant-related covariates. Recurrence of PSC leads to higher number of re-transplantations and a 33% decrease in 10-year graft survival