Chronic high Epstein–Barr virus load carriage: Do liver transplant recipients fare better than heart recipients?

The significance of the chronic high Epstein– Barr virus (EBV) load state after organ transplantation has been a matter of ongoing discussion and concern since its initial recognition. In this issue of the Journal, Green et al. (1) review their experience with chronic carriage of EBV in liver transplant recipients and appear to show a markedly better outcome compared to their institutional experience in heart transplant recipients with respect to the development of post-transplant lymphoproliferative disorder (PTLD). The management of the entity recognized as PTLD continues to be a challenge for clinicians (2, 3). This condition is most often associated with EBV. In some transplant centers, EBV disease/PTLD rivals or has surpassed cytomegalovirus (CMV) in terms of clinical burden. In such situations, clinicians are not only faced with managing PTLD when it does occur, but the threat of PTLD itself poses management challenges. In this context, attempts to reduce immunosuppression in an attempt to preemptively manage EBV infection may result in rejection and graft loss. Post-transplant lymphoproliferative disorder represents the uncontrolled proliferation of EBV-transformed lymphocytes. In healthy persons, the tendency for these transformed cells to proliferate is inhibited by cytotoxic T lymphocytes (CTL) and natural killer cells. In the vast majority of cases of PTLD, the proliferating cells are B lymphocytes. PTLD is associated with variable morbidity and mortality among different groups of transplant recipients. Children are known to be at risk because of the greater likelihood of primary EBV infection occurring as a result of receiving an EBV-seropositive organ when they themselves are often EBV-seronegative (4). In primary EBV infection after transplantation, patients have no existing immunity in the form of EBV-specific CTL surveillance activity. Among transplant recipients, the best strategy to prevent PTLD has not yet been established. Approaches that have been used with variable success include alteration in immunosuppression, and/or antivirals and immune globulin, either singly or in combination. These approaches are often triggered by elevated peripheral blood viral loads. Epstein–Barr virus load is measured by polymerase chain reaction of EBV genomes (5). Controversy exists regarding the optimal blood component that should be used to determine viral load (6, 7). Such determination may be done on DNA extracted from whole blood, plasma, serum, or peripheral blood mononuclear cells. Whole blood and peripheral mononuclear cells are the most frequently accepted specimens to be used for viral load determination (7). In immunosuppressed patients, elevated viral loads may predict complications secondary to EBV. In the transplant recipients, the ability of viral load to predict PTLD is limited by the fact that the specificity is low. Viral load is better at ruling outEBV-drivenPTLD than in indicating its presence (5, 8, 9). In this regard, elevated viral loads do not always correlate with the presence of PTLD or the likelihood that PTLD will develop. On theother hand, transplant recipientswith a low viral load are less likely to have PTLD. Viral load measurements reflect the amount of EBV-infected cells in the peripheral blood. The majority of these cells are believed to exist in the transformed state as opposed to the lytic phase. It is believed that in immunosuppressed patients such as transplant recipients, transformed B cells proliferate in lymphoid tissues and migrate into the peripheral blood. A high viral load measurement clearly represents an abnormal state. However, the meaning of a high viral load and the likely consequences will Pediatr Transplantation 2009: 13: 268–271 2008 John Wiley & Sons A/S.