Tacrolimus Trough Concentrations are Not Impacted by Epstein-Barr Virus Serology and Viral Load in Pediatric Liver Transplant Recipients.

Abstract

Background and objectives: Epstein-Barr virus (EBV) is a common herpesvirus among pediatric liver transplant recipients, but it can have serious complications, such as post-transplant lymphoproliferative disease. EBV is hypothesized to influence tacrolimus concentrations by increasing inflammatory cytokines that regulate the expression of cytochrome-P-450 enzymes involved in tacrolimus pharmacokinetics. This study aims to examine the association between EBV serostatus and viral load, and tacrolimus trough concentrations corrected for the dose and recipient weight [weight-adjusted concentration-to-dose (C/D) ratios].

Materials and methods: This retrospective study includes pediatric liver transplant recipients aged 0-18 years old, transplanted at the University Medical Center Groningen between January 2008 and September 2021. This study utilized two cohorts: a cross-sectional and a longitudinal study database.

Results: The association between EBV serostatus and the tacrolimus pharmacokinetics was examined using 45 recipients from both cohorts. The effect of EBV viral load on tacrolimus pharmacokinetics was examined using the longitudinal study database, which included 25 EBV-positive recipients. No significant effect of EBV on the tacrolimus weight-adjusted C/D ratios was found, for either EBV serostatus (p = 0.85) or EBV viral load (p = 0.85).

Conclusions: This study suggests that the standard protocol of tacrolimus dosing does not seem to require adjustments due to changes in EBV serostatus or viral load.