Significance of detecting epstein-barr-specific sequences in the peripheral blood of asymptomatic pediatric liver transplant recipients

Abstract

Pediatric allograft recipients are at increased risk for Epstein-Barr virus (EBV)-associated illnesses. The early identification and diagnosis of EBV-associated disorders is critical because disease progression can often be curtailed by modification of immunosuppression. We have previously shown that detection of EBV-specific sequences in the circulation by polymerase chain reaction (PCR) correlated well with the clinical symptoms of EBV infection. The purpose of the current study is to determine the significance of detecting EBV-specific sequences by PCR in asymptomatic pediatric liver transplant recipients. Peripheral-blood DNA was analyzed for the EBV genes, coding from the nuclear antigen 1 (EBNA-1) and the viral capsid antigen (gp220) by PCR. Samples from asymptomatic pediatric liver transplant recipients were analyzed from the immediate postoperative period and at 2-to 4-month intervals thereafter. We followed up 13 of these asymptomatic recipients who tested positive for EBV compared with 7 asymptomatic recipients who tested negative for EBV during the early posttransplantation period. Follow-up ranged from 1.5 to 4 years posttransplantation. Nine patients (69%) initially positive for EBV and asymptomatic ultimately developed symptoms of EBV infection, including fever, lymphadenopathy, rash, respiratory and gastrointestinal symptoms, and/or hepatitis. Five of these patients (56%) went on to develop posttransplant lymphoproliferative disorder based on histological examination of biopsied tissue and immunohistochemical identification of the EBV antigen/DNA in tissue. This is the first report suggesting that detection of EBV-specific sequences in the absence of symptoms may herald impending EBV-associated disorders. Thus, routine monitoring for circulating EBV sequences in asymptomatic recipients may be useful in the early identification of those at risk for developing EBV-associated disease and its ultimate prevention.

Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation (SCT) and quantitatively predicts EBV-lymphoproliferative disease following T-cell–depleted SCT

“…[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] No study, however, has longitudinally followed allo-SCT recipients with multiple risk factors from day 0 until day 180 and reported positive and negative predictive values. Lucas et al 41 evaluated the predictive value of quantitative PCR using DNA extracted from peripheral blood For personal use only.…”

“…25,26 In contrast to cytomegalovirus (CMV) antigenemia after allo-SCT and the risk of developing CMV disease, little is known about reactivation of EBV during the first 3 to 6 months after allo-SCT and the predictive value of EBV reactivation for subsequent EBV-LPD. Although several studies have shown an association between viral load and a diagnosis of EBV-LPD, [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] no study has longitudinally followed a larger cohort of allo-SCT recipients with multiple risk factors. We set out to monitor EBV reactivation by real-time PCR at regular intervals after allo-SCT.…”

Transplante hepático pediátrico: experiência de 10 anos em um único centro no Brasil

“…13 The great majority of biliary complications are secondary to thrombosis of the hepatic artery, 28 and were observed in 7.1% of our cases, which is comparable to what is reported in the literature (5 to 30%). 3 One of our patients had lymphoproliferative disease (2.3%), which is described as affecting 5 to 15% of children after transplantation, 10,22,29,30 The principal causes of immediate repeat transplants are primary non-function of the graft and thrombosis of the hepatic artery, 3,8,13,18,22 while, over the long term, chronic rejection is the number one indication. 8 In our sample there were two repeat transplants due to thrombosis of the hepatic artery.…”

Posttransplant Lymphoproliferative Disorders Following Solid Organ Transplantation

“…(Lee, et al 2005) Series of pediatric intestinal transplant recipients reported similar results. (Green et al, 2000;Krieger, et al 2000) Rituximab is generally well tolerated and rapidly induces the depletion of mature B-lymphocytes, reducing the compartment of EBV infected cells, with an associated normalization of the viral load. It has been successfully used as a preemptive treatment for PTLD, specifically in the HSCT population.…”