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 nested polymerase 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 1st year after liver transplantation (LTX). The findings were related to liver histology and results of EBV-nPCR on concomitantly obtained serum samples. EBV DNA was detected in 30% and RNA in 34% of the liver biopsy specimens using nPCR and EBER-ISH, respectively, giving a significant correlation between the two methods (P = 0.003). All but one patient had detectable EBV DNA in serum samples obtained within 1 month of the biopsy. More than 90% of the nPCR and EBER-ISH-positive biopsy specimens were obtained 3 months or less post-LTX. There was no significant difference in EBV genome findings in biopsy specimens with or without lymphocytic-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 negative in ISH. Histopathological changes in EBV hepatitis may be nonspecific and masked by other complications. The use of EBV-nPCR and EBER-ISH in liver graft biopsy specimens of heavily immunosuppressed patients may give an early indication of EBV-related disease and can be used to guide therapeutic intervention.