OKT3 and ganciclovir treatments are possibly related to the presence of Epstein-Barr virus in serum after liver transplantation

Abstract

The development of Epstein-Barr virus (EBV) associated lymphoproliferative disorder (PTLD) is related to EBV genome numbers in serum or plasma and B-cells, and the level of immunosuppression. EBV DNA viremia, defined as presence of EBV genomes in serum or plasma, is common in immunodeficiency. This survey of EBV viremia was performed by real-time polymerase chain reaction (PCR) on consecutive serum samples of 21 patients with acute (n = 3) or chronic liver disease (n = 18) during the first year after liver transplantation (LTX). Cytomegalovirus (CMV) DNA was analyzed with PCR in serum or leukocytes. The levels of EBV and CMV viremia were related to PTLD and the effect of different anti-rejection regimens. All patients were EBV-seropositive pre-LTX. In total, 24 of 152 (16%) samples from 10 of 21 (48%) individuals were EBV positive [five of 11 cyclosporin A (CsA); five of 10 tacrolimus treated cases]. EBV viremia was demonstrated in five of seven patients with OKT3 therapy. The number of EBV DNA positive samples was highest (26%) at 14 days after LTX. In the OKT3 treated groups, the medians of EBV DNA copy numbers were 1600/ml (range 230-7200) and 380/ml (range 120-860) in the CsA and tacrolimus patients, respectively (P < 0.02). One patient developed EBV lymphoma and another one EBV hepatitis 13 months and 24 days post-LTX, respectively. Both patients had received OKT3. Their EBV genome load was not significantly different from what was found in other patients. After ganciclovir therapy, EBV DNA was eradicated from serum in four of five patients for several months. EBV DNA load was not affected by CMV infection or disease. We conclude that presence of EBV in serum is a possible marker of an active infection and an early ganciclovir therapy may be beneficial. Quantification of EBV load offers the potential to implement pre-emptive interventions.