title: Role of hepatitis B virus base core and precore/core promoter mutations on hepatocellular carcinoma in untreated older genotype C Chinese patients.
abstract: The aim of the study was to investigate the prevalence of mutations of basal core promoter (BCP) and precore (PreC) region of hepatitis B virus (HBV) and their association with hepatocellular carcinoma. A total of 341 untreated older HBV patients were divided into three groups: chronic hepatitis B (CHB, 185), cirrhotic hepatocellular carcinoma (LC-HCC, 113) and non-cirrhotic hepatocellular carcinoma (non-LC-HCC, 43). HBV BCP and PreC mutations and genotypes were determined by direct sequencing. Using univariate analysis, age (≥ 45 years), single mutations including A1896 and A1899 and multiple mutations T1762/A1764 + A1896, T1762/A1764 + A1899 and T1762/A1764 + A1896 + A1899 were more frequently detected in LC-HCC and non-LC-HCC patients than in CHB patients. BCP T1762/A1764 mutations were highly detected in LC-HCC patients than in CHB patients. Multivariate logistic regression analysis (adjusted for age and gender) revealed that among HBeAg-positive patients, BCP T1762/A1764 mutations (OR, 5.975; P = 0.05), PreC A1899 mutation (OR, 4.180; P = 0.013) and multiple mutations T1762/A1764 + A1899 (OR, 6.408; P = 0.006) were independently associated with the development of LC-HCC; PreC A1899 mutation (OR, 7.347; P = 0.034) was also independently associated with the development of non-LC-HCC. On the other hand, among HBeAg-negative patients, PreC A1896 mutation (OR, 5.176; P = 0.002) and multiple mutations T1762/A1764 + A1896 (OR, 4.149; P = 0.007) were independently associated with the development of non-LC-HCC. These results indicated that older age (≥ 45 years) was associated with LC-HCC and non-LC-HCC development. BCP T1762/A1764 mutations and PreC A1899 mutation were associated with the LC-HCC development in HBeAg-positive patients. PreC A1896 mutation was associated with the non-LC-HCC development in HBeAg-negative patients.
authors.affiliation: Laboratory of Virology, Department of Infectious Diseases, Peking University First Hospital, Beijing, China.
authors.forename: J-X
authors.initials: JX
authors.lastname: Zheng
authors.forename: Z
authors.initials: Z
authors.lastname: Zeng
authors.forename: Y Y
authors.initials: YY
authors.lastname: Zheng
authors.forename: S-J
authors.initials: SJ
authors.lastname: Yin
authors.forename: D-Y
authors.initials: DY
authors.lastname: Zhang
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Yu
authors.forename: F
authors.initials: F
authors.lastname: Wang
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D002681:China / Q000453:epidemiology; D005260:Female; D005838:Genotype; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics / Q000472:pathogenicity*; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D006512:Hepatitis B Core Antigens