Role of hepatitis B virus base core and precore/core promoter mutations on hepatocellular carcinoma in untreated older genotype C Chinese patients

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http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2893.2011.01458.x/abstract

Role of hepatitis B virus base core and precore/core promoter mutations on

hepatocellular carcinoma in untreated older genotype C Chinese patients

J-X. Zheng, Z. Zeng, Y. Y. Zheng, S-J. Yin, D-Y. Zhang, Y-Y. Yu, F. Wang

Article first published online: 4 APR 2011

DOI: 10.1111/j.1365-2893.2011.01458.x

© 2011 Blackwell Publishing Ltd

Issue

Journal of Viral Hepatitis

Early View (Online Version of Record published before inclusion in an issue)

Summary.  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.