Frequent detection of hepatitis B virus X-gene DNA in hepatocellular carcinoma and adjacent liver tissue in hepatitis B surface antigen-negative patients

Hepatitis B virus is associated with human hepatocellular carcinoma. We performed polymerase chain reaction for the X, C, S, and preS2/S regions of the viral genome in 23 hepatitis B surface antigen-negative hepatocellular carcinomas and adjacent liver. Hepatitis B viral genomes were detected in 17 of 23 tumors and adjacent tissues(73.9%). Among recognized transactivators, the X gene was present in 16 (69.6%) cases of hepatocellular carcinoma, but preS2/S was detected in only 7 (30.4%). Hepatitis B virus C and S regions were detected in 3 (13.0%) and 9 (39.1%) hepatocellular carcinomas, respectively. Serologic study revealed antibodies to hepatitis B surface antigen, hepatitis B core antigen, and hepatitis B e antigen in 14 patients; among these, X-gene DNA was detected in 12 of 14 tumors (85.7%). The X gene was also detected in 4 of 9 tumors of seronegative patients. The X gene, present in many hepatocellular carcinomas, may promote hepatocellular carcinoma in hepatitis B surface antigen-negative patients.