The Effect of Sirolimus Immunosuppression on Cardiovascular Outcomes in Liver Transplantation

Introduction

Non-alcoholic steatohepatitis (NASH) is a rising cause of liver transplantation and is linked to higher rates of cardiovascular complications. The aim of this study was to evaluate the risk of post-transplant cardiac events in patients with NASH that were exposed to sirolimus (SRL) vs. calcineurin-inhibitor (CNI) immunosuppression.

Methods

We retrospectively reviewed all adult liver transplant recipients at our institution between 2002 and 2020. Subjects were grouped based on immunosuppressive regimen. We also analyzed the subgroup of patients with NASH as the primary indication for transplant, as well as a non-NASH subpopulation. The primary outcome measure was risk of major adverse cardiovascular events (MACE) post-transplant. Comparisons between groups were conducted with chi-squared tests. Univariate Cox regression and multivariate time-dependent Cox regression models were used to analyze the relationship between immunosuppression and MACE risk.

Results

803 liver transplant patients met criteria for study inclusion. Of these, 169 patients had NASH as their primary indication for liver transplant. 18 % of the study population received SRL immunosuppression post-transplant, and the remainder received only CNI immunosuppression. Post-transplant MACE occurred in 32.65 % of patients on SRL compared to 10.27 % in patients on CNI immunosuppression (p =< 0.001). Without taking development of post-transplant CKD into account, our study showed a significantly higher risk of MACE with SRL immunosuppression in both the non-NASH cohort (HR 1.67, p = 0.036) and the NASH cohort (HR 2.48, p = 0.037. However, when accounting for post-transplant CKD, our analysis of the Non-NASH and NASH cohorts did not show a significantly greater risk of post-transplant MACE with SRL compared to CNI immunosuppression.

Conclusions

Our analysis shows that in both the NASH and non-NASH cohorts, liver transplant patients on sirolimus did not have a significantly higher risk of developing cardiovascular disease after transplant compared to immunosuppression with calcineurin inhibitors.