Response of elevated Epstein-Barr virus DNA levels to therapeutic changes in pediatric liver transplant patients: 56-month follow up and outcome

Posttransplant lymphoproliferative disease (PTLD) is a serious complications after liver transplantation. Epstein-Barr virus (EBV) load measured by quantitative competitive polymerase chain reaction (PCR) has been used as an early marker for the development of PTLD and a guide for initiating preemptive therapy. The aim of this study is to report the results of EBV DNA PCR screening in a transplant population and to examine the risk factors for developing elevated EBV DNA PCR and the effect of interventions for reducing EBV DNA levels. Medical records of 44 children who underwent liver transplantation and EBV DNA PCR screening during a 3-year period were reviewed, and the patients were prospectively followed up for another 2 years. Eleven patients who developed elevated EBV DNA PCR levels, defined as >/=40 genomes/105 peripheral blood lymphocytes (PBL) in pretransplant EBV-seronegative patients and >/=200 genomes/105 PBL in pretransplant-seropositive patients, were treated. The initial intervention was reduction of immunosuppression and initiation of anti-viral therapy in all patients, with administration of cytomegalovirus immunoglobulin (CMV-IgG) in two patients. CMV-IgG was then given to five of the patients who did not respond to the initial intervention. The initial intervention resulted in the reduction of EBV DNA PCR levels to below threshold values in 4 of 11 patients. Five patients who did not respond to the initial interventions were subsequently given intravenous CMV-IgG. The EBV DNA PCR level fell in all five of these patients during the course of treatment with CMV-IgG, with a significant reduction (to threshold levels or by two dilutions) in four of the five patients. No episodes of graft rejection were observed. Eleven patients (25%) developed elevated EBV DNA PCR after liver transplantation. There were no identifiable risk factors for developing elevated EBV DNA PCR. A combination of reducing immunosuppression, adding antiviral agents, and initiating CMV-IgG resulted in a significant reduction of EBV DNA levels in nine (82%) patients during the follow-up period.