Risk factors and long-term outcomes of pediatric liver transplant recipients with chronic high Epstein-Barr virus loads

Background: Serial monitoring of Epstein-Barr virus (EBV) reveals that certain pediatric liver transplant (LT) recipients exhibit high EBV loads for long periods. We investigated the incidence and risk factors of chronic high EBV (CHEBV) loads (continuous EBV DNA >10 000 IU/mL of whole blood for ≥6 months) and long-term outcomes. Methods: This single center, retrospective observational study investigated pediatric LT recipients who survived ≥6 months. We quantitated EBV DNA weekly during hospitalization and subsequently every 4 or 6 weeks at the outpatient clinic. Tacrolimus was maintained at a low trough level (<3 ng/mL, EBV DNA load >5000 IU/mL). Results: Thirty-one of 77 LT recipients developed CHEBV. Univariate analysis revealed that age <2 years and body weight <10 kg upon LT, operation time <700 minutes, warm ischemia time (WIT) >35 minutes, graft-to-recipient weight ratio (GRWR) >2.7%, and preoperative EBV seronegativity were significantly associated with the development of CHEBV loads. Multivariate analysis identified significant associations of CHEBV with WIT >35 minutes, GRWR >2.7%, and preoperative seronegative. None of the recipients developed post-transplantation lymphoproliferative disorder. Survival rates of patients with and without CHEBV loads were not significantly different. Conclusions: A significant number of pediatric LT recipients developed CHEBV loads. Long WIT, high GRWR, and preoperative EBV seronegativity were significantly associated with the development of CHEBV loads. Although the long-term outcomes of patients with or without CHEBV loads were not significantly different, further studies of more subjects are warranted.