POLYMERASE-CHAIN-REACTION AND IN-SITU HYBRIDIZATION OF EPSTEIN-BARR-VIRUS IN LIVER-BIOPSY SPECIMENS FACILITATE THE DIAGNOSIS OF EBV HEPATITIS AFTER LIVER-TRANSPLANTATION

A nestedpolymerase chain reaction (nPCR) for Epstein-Barr virus (EBV) DNA, RNA in situ hybridization (EBER-ISH), and immunostaining against the ZEBRA EBV protein for diagnosis of EBV hepatitis were performed on 43 liver biopsy specimens obtained from 18 patients in the Ist year a fter liver transplantation (LTX). The findings were related to liver h istology and results of EBV-nPCR on concomitantly obtained serum sampl es. EBV DNA was detected in 30 % and RNA in 34 % of the liver biopsy s pecimens using nPCR and EBER-ISH, respectively, giving a significant c orrelation between the two methods (P = 0.003). All but one patient ha d detectable EBV DNA in serum samples obtained within 1 month of the b iopsy. More than 90 % of the nPCR and EBER-ISH-positive biopsy specime ns were obtained 3 months or less post-LTX. There was no significant d ifference in EBV genome findings in biopsy specimens with or without l ymphocytic-immunoblastic infiltrates, either in nPCR (P = 0.73) or in ISH (P = 0.73). TWO of three biopsy specimens with these histological changes suggesting a viral genesis were positive in EBV-nPCR but negat ive in ISH. Histopathological changes in EBV hepatitis may be nonspeci fic and masked by other complications. The use of EBV-nPCR and EBER-IS H in liver graft biopsy specimens of heavily immunosuppressed patients may give an early indication of EBV-related disease and can be used t o guide therapeutic intervention.