CHARACTERISTICS OF EPSTEIN-BARR VIRUS PRIMARY INFECTION IN PEDIATRIC LIVER TRANSPLANT RECIPIENTS

Abstract

41 Background: Pediatric liver transplant recipients are at high risk of Epstein-Barr virus (EBV) infection following surgery. However the incidence of clinical symptoms and the graft function at the time of acute infection remains poorly documented. We report here the characteristics of primary EBV infection when occurring in pediatric liver transplant recipients. Patients and methods: Clinical and biological patterns associated with EBV infection were systematically searched in a cohort of 38 liver transplanted children (median age at OLT 20 months, range 5-158) between 1996 and 1998. Diagnosis of EBV infection was made by detection of EBV genome in peripheral blood lymphocytes using polymerase chain reaction (PCR) and/or by detection of anti-VCA IgM antibodies. Echography was used to detect abdominal lymphoid tissue. Results: Only 5 children (13%) had pretransplant immunity for EBV. Twenty-six (68.5%) developed primary EBV infection within a median of 30 days (range 15-90) following OLT. Ten had positive PCR with negative IgM. Sixteen patients had positive IgM among which PCR was positive whenever tested (n=5). Seven (18.5%) remained EBV negative on follow-up. Four (15%) had clinical symptoms at the time of infection, including necrotic tonsilitis (n=3) and impaired general condition (n=2). Two of them had concomitant PTLD liver nodules (n=2). A third PTLD occurred in one additional patient (gastric involvement) 300 days after primary asymptomatic infection. Overall incidence of PTLD was 10.5%. All three over-PTLD had full recovery following arrest of immunosuppression, one of them treated with anti-CD 20 antibodies (Mabthera®, Roche, Switzerland). No single patient had abnormal liver function tests (AST, ALT, GammaGT) related to EBV infection. Three of four PTLD had hypergammaglobulinemia, but only one of 34 non PTLD patient (cystic fibrosis). Conclusion: EBV primary infection occurs in 80% of seronegative patients within 3 months after OLT. PCR is more reliable than IgM for early diagnosis. Infection is not associated to changes of LFT's. A minority (15%) have clinical symptoms, being at high risk of full PTLD. Hypergammaglobulinemia is closely associated with PTLD.