Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers.
OBJECTIVE
Hepatitis B viral (HBV) genotype C is associated with the development of hepatocellular carcinoma (HCC) compared with genotype B; however, the virologic factors contributing to the pathogenic differences remain unknown. We investigated the prevalence of T1762/A1764 basal core promoter mutant in a cohort of 250 genotype B- or C-infected HBV carriers with different stages of liver disease to clarify a possible role for this mutant in hepatocarcinogenesis.


METHODS
The sequences of basal core promoter of HBV genome were determined in 60 inactive HBV carriers and 190 patients with histologically verified chronic liver disease and HCC.


RESULTS
Genotype C has a higher prevalence of T1762/A1764 mutation than genotype B (odds ratio, 5.18; 95% confidence interval [CI], 2.59-10.37; P < 0.001). The likelihood of T1762/A1764 mutation parallels the progression of liver disease, from 3% in inactive carriers to 64% in HCC patients (odds ratio, 20.04; 95% CI, 7.25-55.41; P < 0.001). By multiple logistic regression analysis, patients with T1762/A1764 mutation were significantly associated with the development of HCC than those without (odds ratio, 10.60; 95% CI, 4.92-22.86; P < 0.001), and the risk was observed for both genotypes B and C. In addition, the prevalence of T1762/A1764 mutation in younger HCC patients was comparable with older HCC patients but was significantly higher than that in age-matched inactive carriers, irrespective of genotypes.


CONCLUSIONS
Our data suggest that HBV carriers with T1762/A1764 basal core promoter mutant are at increased risk for HCC and that this mutant may contribute to the pathogenesis of HBV infection.
Kao
Jia-Horng
JH
Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. kjh@ha.mc.ntu.edu.tw
Chen
Pei-Jer
PJ
Lai
Ming-Yang
MY
Chen
Ding-Shinn
DS
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D002353:Carrier State; D015331:Cohort Studies; D005260:Female; D005814:Genes, Viral / Q000235:genetics; D006509:Hepatitis B / Q000150:complications*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D014758:Viral Core Proteins / Q000235:genetics*
D014758:Viral Core Proteins