Epstein-Barr Virus—Associated Posttransplantation Lymphoproliferative Disorder With Tacrolimus Metabolism Deterioration in Infants After Living-Donor Liver Transplantation

BACKGROUNDPosttransplantation lymphoproliferative disorder (PTLD) in infants after liver transplantation is strongly associated with tacrolimus (Tac) administration and primary Epstein-Barr virus (EBV) transmission. METHODSFrom 1991 to 2012, 32 survivors younger than 2 years who had undergone living-donor liver transplantation using Tac for primary immunosuppression were retrospectively investigated for changes in Tac trough levels before and at the onset of posttransplantation viral infection episodes. RESULTSTwenty-one recipients experienced 33 viral infection episodes associated with EBV-related PTLD (n=5), symptomatic EBV infection without development of PTLD (n=8), and other viral infections (n=20). Although the average Tac trough levels during the 2 months before the onset of viral infection episodes were similar among the 33 episodes (9.0±2.8 ng/mL), the Tac trough levels at the onset were significantly higher in the episodes with PTLD than in those with EBV infection without the development of PTLD and with other viral infections (19.2±9.0 ng/mL vs. 9.3±5.2 ng/mL and 10.6±5.1 ng/mL, respectively) (P