Sequential accumulation of the mutations in core promoter of hepatitis B virus is associated with the development of hepatocellular carcinoma in Qidong, China

Background/Aims: To investigate the mutations in hepatitis B virus (HBV) that might be related to hepatocellular carcinoma (HCC) in the high-risk area Qidong, China. Methods: DNA sequences of HBV basal core promoter (BCP) and the overlapping X gene were determined in 58 HCC and 71 chronic hepatitis (CH) patients. In addition, a consecutive series of plasma samples from 15 HCC cases were employed to compare the CP/X sequences before and after the occurrence of HCC. Results: T1762/A1764 double mutation was frequently found in Qidong patients, regardless of clinical status (65.5% in HCC and 73.2% in CH, P > 0.05). Unexpectedly, the adjacent T1766/A1768 mutation significantly increased the risk of HCC (P < 0.05). Moreover, the prevalence of triple mutations in BCP was significantly higher in patients with HCC than those with CH (P < 0.05). The longitudinal study demonstrated that the mutations in BCP were gradually accumulated during the development of HCC. Colony formation assay showed while A1764 mutation alone did not alter the colony-inhibitory activity of HBx, double or triple mutations largely abrogated this effect. Conclusions: The complex mutation involving T1766/A1768 was closely related to HCC. The enhanced risk of HCC caused by BCP variants could be attributable partially to the aberrant activity of HBx. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.