Epstein-Barr virus--associated posttransplantation lymphoproliferative disorder with tacrolimus metabolism deterioration in infants after living-donor liver transplantation.
BACKGROUND
Posttransplantation lymphoproliferative disorder (PTLD) in infants after liver transplantation is strongly associated with tacrolimus (Tac) administration and primary Epstein-Barr virus (EBV) transmission.


METHODS
From 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.


RESULTS
Twenty-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<0.05). Tacrolimus trough levels at the onset of PTLD were significantly higher during the 2 months before the onset (median, 1.83 times higher than average) compared with EBV infection (1.14 times higher) and other viral infections (1.06 times higher) (P<0.05). The Tac blood concentration-to-dose ratio at the onset of PTLD was more than twice as high as the average value during the 2 months before the onset.


CONCLUSIONS
Deteriorated Tac metabolism accompanied by a positive change in the blood EBV DNA load may enable us to predict the development of PTLD in liver-transplanted infants with viral infection.
1 Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan.
Daizo
D
Fukushima
Kazushige
K
Sato
Naoki
N
Kawagishi
Noriaki
N
Ohuchi
Susumu
S
Satomi
D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D016903:Drug Monitoring; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000175:diagnosis / Q000821:virology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D007223:Infant; D016031:Liver Transplantation / Q000009:adverse effects*; D019520:Living Donors; D008232:Lymphoproliferative Disorders / Q000097:blood / Q000175:diagnosis / Q000821:virology*; D008297:Male; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics*; D019562:Viral Load
D015415:Biomarkers; D004279:DNA, Viral; D007166:Immunosuppressive Agents; D016559:Tacrolimus