Epstein-Barr virus DNA in serum after liver transplantation ? surveillance of viral activity during treatment with different immunosuppressive agents

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Abstract
In immunocompromised HIV-infected and transplanted patients, there is a risk of developing Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPD) and lymphomas. EBV has previously been detected by the polymerase chain reaction (PCR) in cerebrospinal fluid from all AIDS patients with EBV-associated cerebral lymphomas. We therefore thought it would be of interest to determine whether transplant patients with extracerebral EBV-associated LPD have detectable EBV genomes in serum. Nested PCR (nPCR) showed that 58% (18/31) of liver transplant (LTX) patients had EBV DNA in 17% (21/125) of serum samples obtained within the first 3 months after LTX. In 39% (7/18) of the patients, the first EBV nPCR-positive sample was found within 2 weeks post-LTX. Basic immunosuppression with cyclosporin A or FK506 did not seem to influence the frequency of detectable EBV genomes in serum. In contrast, positive EBV nPCR correlated to secondary OKT3 treatment for severe acute rejection (P = 0.009). EBV-associated malignant lymphoma developed in three patients 2-6 months post-LTX. In all of them, EBV DNA was amplifiable within 12-14 days after LTX. The EBV antibody titers were not directly related to detectable EBV DNA in serum. We conclude that monitoring of LTX patients receiving increased immunosuppression by nPCR for EBV DNA in serum may help in the early identification of those at risk of developing EBV-associated LPD.

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