Impact of immunosuppression on the development of Epstein Barr Virus (EBV) viremia after pediatric liver transplantation

Background: Pediatric liver transplant patients are at increased risk of post transplant lymphoproliferative disease (PTLD) from Epstein Barr virus (EBV) infection or reactivation after transplantation. The goal of this study was to determine the impact of induction and immunosuppression levels on the development of EBV viremia post transplantation. Methods: A retrospective chart review was performed on 104 patients less than 18 years of age who underwent isolated liver transplantation (LT) between 2000-2008 at Lucile Packard Children’s Hospital at Stanford University. Induction regiment, immunosuppression levels, and EBV viremia, as noted by any positive value of EBV polymerase chain reaction testing, was documented for one year post transplantation. Fixed-effects logistic regression models were constructed to determine associations between induction therapy, immunosuppression levels, and EBV viremia. A P-value < 0.05 was considered to be statistically significant. All statistical analyses were performed using STATA 11 (College Station, TX). Results: 56% of patients developed EBV viremia within one year of LT. Patients were more likely develop EBV viremia if they had received either anti-thymocyte globulin [ATG (73%)] or daclizumab (63%) for induction versus neither (39%), though the trend was not statistically significant (ATG: Odds ratio (OR) 0.19; 95% CI 0.024 – 1.58; p = 0.125; daclizumab: OR: 1.07; 95% CI 0.270 – 4.23; p=0.925). Tacrolimus immunosuppression levels were supratherapeutic 37% of the time within the first three months of transplant; however, only supratherapeutic tacrolimus levels between 0-2 weeks after transplant impacted the development of EBV viremia at 2-4 weeks post LT (OR 1.80; 95% CI 1.10-2.94; p=0.02). Only one patient developed PTLD during the study period. Conclusion: The type of induction used in isolated pediatric LT may play a role in the development of EBV viremia, with ATG and daclizumab leading to a higher incidence of EBV viremia, though it was not statistically significant. Supratherapeutic immunosuppression tacrolimus levels 0-2 weeks post LT impacted the development of EBV viremia at 2-4 weeks, but the effect was not seen at other time intervals. The incidence of PTLD in our study was low, suggesting better EBV and immunosuppression monitoring has played an important role in the reduction of complications associated with EBV viremia post pediatric LT.