No direct role for Epstein-Barr virus in American hepatocellular carcinoma

Epstein-Barr virus (EBV) was recently linked to hepatocellular carcinogenes is in Japanese patients. It is not clear whether EBV infection is also asso ciated with hepatocellular carcinoma (HCC) occurring in American patients. We studied 41 cases of HCC from the Los Angeles area for evidence of EBV in fection by in situ hybridization, immunohistochemistry, and polymerase chai n reaction methods. Of 41 cases, 16 were seropositive for hepatitis B virus surface antigen (39%), 9 of 29 tested were seropositive for hepatitis C vi rus antibody (31%); in total, 22 cases were seropositive for hepatitis B vi rus and/or hepatitis C virus (53%). Of 41 cases, 1 was positive for EBV-enc oded small nonpolyadenylated RNA (EBER)-1 (2%) by in situ hybridization. By immunohistochemistry, two cases were positive for EBV nuclear antigen (EBN A)-1 (5%), one was positive for the transactivating immediate early BZLF1 ( ZEBRA) (2%), and none was positive for latent membrane protein-1. None of t he 41 cases was positive for latent membrane protein-1 and EBV nuclear anti gen (EBNA)-4 DNAs by polymerase chain reaction assay. All four positive cas es showed rare EBER-1-, ZEBRA-, or EBNA-1- positive cells (<0.1%); in none of these cases was there expression of any other EBV viral genes. in the on e case each that was positive for EBER-1 and ZEBRA, both of which occurred in patients of non-Asian ethnicity, the staining was limited to infiltratin g small lymphocytes, and tumor cells were negative. In the two cases that w ere positive for EBNA-1, both of which occurred in patients of Asian ethnic ity, the staining was limited to tumor cells, and infiltrating small lympho cytes were negative. Our study indicates that rare cases of American HCC ma y contain EBV-infected cells, but it is unlikely that EBV plays a major rol e in the carcinogenesis of HCC.