Occult hepatitis B virus infection in HBs antigen-negative hepatocellular carcinoma in a Japanese population: Involvement of HBx and p53

Hepatitis B virus (HBV) genome was reported to be detected in serum or live r tissues in hepatocellular carcinoma (HCC) patients negative for hepatitis B surface antigen (HBsAg). Hepatitis B x (HBx) and p53 protein were report ed to play an important role in HBV-related hepatocarcinogenesis. To clarif y latent HBV infection in HBsAg- and anti-hepatitis C virus (anti-HCV)negat ive HCC in a Japanese population and involvement of HBx and p53 protein in these patients, we performed the sensitive and specific nested polymerase c hain reaction (PCR) and immunohistochemical analysis. Of 7,024 HCC patients we saw between 1974 and 1998, 66 (6.4%) were negative for HBsAg and anti-H CV. Serum DNA was amplified by nested PCR by using specific primers of surf ace (S), core (C) and X regions in 26 patients negative for HBsAg and anti- HCV. Eighteen (69%) patients were positive for either S, C, or X region and the results of PCR were confirmed by Southern blotting. Of 18 PCR-positive patients, 3 were positive for anti-HBs and 9 were positive for anti-HBc, h owever, one was negative for any HBV markers. In HBsAg-negative and PCR-pos itive patients, the positive rates of expression of HBx and p53 were 8/13 ( 62%) and 7/13 (54%), being comparable to those in HBsAg-positive HCC patien ts. The results of the present study suggest that high prevalence of HBV in fection is observed in HBsAg-negative HCC in a Japanese population and expr ession of HBx and p53 is consistent with a role, in these patients, for the transforming ability of these proteins. (C) 2000 Wiley-Liss, Inc.