Influence of Tacrolimus Intrapatient Variability on Allograft Rejection Frequency and Survival Following Liver Transplantation.

Abstract

Tacrolimus is the primary calcineurin inhibitor used in immunosuppressive regimens to prevent allograft rejection (AR) after organ transplantation. Recent studies have linked intrapatient variability (IPV) of tacrolimus with AR occurrence and reduced survival, especially in kidney transplant recipients. However, limited data are available on the impact of tacrolimus IPV on adverse outcomes after liver transplantation (LT). The aim of this study was to assess the association between tacrolimus IPV using various methodologies with acute AR and long-term patient survival after LT. All patients who underwent LT from January 2010 to July 2021 were retrospectively evaluated. Tacrolimus IPV was calculated for each patient using the mean and SD, mean absolute deviation (MAD), coefficient of variation (CV), and time in therapeutic range (TTR). These measures were then compared with AR within the first 24 months after LT and to long-term survival. Out of 234 patients, 32 (13.7%) developed AR and 183 (78.2%) survived, with a mean follow-up of 101 ± 43 months. Tacrolimus IPV, assessed by mean, SD, MAD, and CV, was 8.3 ± 2.1, 2.7 ± 1.3, 32.0% ± 11.7%, and 39.4% ± 15.4%, respectively. There was no statistically significant correlation between Tacrolimus IPV and AR or survival post-LT. In a large cohort of patients from diverse racial backgrounds, tacrolimus IPV was not associated with clinically relevant outcomes such as AR and survival after LT.