Gastroenterology

Gastroenterology

Volume 124, Issue 2, February 2003, Pages 327-334
Gastroenterology

Clinical–Liver, Pancreas, and Biliary Tract
Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers

https://doi.org/10.1053/gast.2003.50053Get rights and content

Abstract

Background & Aims: 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.

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Supported by grants from the Department of Health and the National Science Council, Executive Yuan, Taiwan.

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