Detection of Epstein-Barr Virus DNA in Hepatocellular Carcinoma Tissues from Hepatitis C-positive Patients

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Abstract
Background: We have previously shown that hepatitis C virus (HCV) replication is promoted by the Epstein-Barr virus (EBV) in vitro. The aim of this study was to examine the EBV load in hepatocellular carcinoma (HCC) tissues from HCV antibody-positive patients. Methods: DNA was extracted from paraffin sections from 168 HCC patients. After amplification of a region in the EBV BamHI W sequence by means of the polymerase chain reaction (PCR), it was detected by Southern hybridization and semi-quantified. Ten hyperplastic lesions from HCV-positive patients and 35 non-tumorous samples from hepatitis-negative patients served as controls. The PCR results were analyzed on the basis of the patient's hepatitis status. Univariate and multivariate analyses were performed to identify clinicopathologic factors for predicting EBV infection in HCC tissues. Results: More than one copy of EBV DNA per 100 cells was detected in 56 (33%) of the HCC sections. The detection ratio in HCC tissues from HCV antibody-positive patients was 40% (45 of 113), which was significantly higher than that in tissues from HBV surface antigen-positive patients (14%, 5 of 37; P = 0.0018). The patient's serum HBV surface antigen and HCV antibody independently predicted the EBV positivity of HCC tissues. Conclusions: These results support our hypothesis that EBV could play an important role in the development of HCV-related HCC.