Impact of Valganciclovir on Epstein-Barr Virus Polymerase Chain Reaction in Pediatric Liver Transplantation: Preliminary Report

Abstract

Preemptive therapy with ganciclovir has been recommended in the pediatric liver transplant strategy to avoid the development of posttransplant lymphoproliferative disorder (PTLD) from an high Epstein-Barr virus (EBV) is detected. We sought viral load to analyze the response to preemptive therapy with valganciclovir (VGC) in children with liver transplantations and an high quantitative EBV-PCR. Methods From June 2005 to December 2007, we tested 979 EBV-PCR among 80 pediatric liver transplant recipients, from those 21/80 PCR were tested from the date of transplantation and 59/80 belonged to the historical cohort (7/59 had a prior history of PTLD). Patients were divided into 2 groups depending upon whether they did ( n = 22) or did not ( n = 19) receive VGC treatment. The response to VGC was considered complete, if the PCR was negative at 30 and 60 days of treatment; and partial, when the PCR decreased at least 50%. Ganciclovir blood levels tested in 109 cases instances and correlated with the EBV-PCR. Results A total of 369 (33%) positive PCR were detected in 36/80 patients (mean, 75,000 copies; range = 5000–4,200,000). Among the 22 episodes treated for 30 days, 34% showed complete responses, 41%, partial, and 23%, no response. Among the non-treated group the rates were 6%, 25%, and 68%, respectively ( P = .01). However, no differences were observed among those episodes treated for 60 days. At the administered doses, hardly any patient reached the recommended ganciclovir therapeutic level at 2 hours (6 μ/mL). However, the mean PCR was lower when the ganciclovir levels were greater than 4 mg/L when compared with lower levels ( P = .03). Conclusion After 30 days of treatment there was a response to VGC in the EBV viral load. There was high interpatient variability of ganciclovir serum concentrations, suggesting the need for pharmacokinetic monitoring to optimize treatment. There was a relationship between the concentration of ganciclovir and the EBV viral load.