Basal core promoter T1762/A1764 and precore A1896 gene mutations in hepatitis B surface antigen-positive hepatocellular carcinoma: a comparison with chronic carriers.
BACKGROUND
Chronic hepatitis B virus (HBV) infection is associated with hepatocellular carcinoma (HCC), and specific viral factors have been identified that may increase the risk for HCC development. However, the differences in these viral factors in chronic carriers who seldom develop HCC compared with HCC patients have not been adequately evaluated.


METHODS
From 1989 to 2005, 101 hepatitis B surface antigen-positive patients presented to our clinic with HCC. Baseline basal core promoter (BCP) T1762/A1764 mutants, precore (PC) A1896 mutants, HBV genotypes and HBV DNA in HCC patients were compared with 67 chronic carriers who had been followed for a mean of 112.1+/-77.7 standard deviation months.


RESULTS
At baseline, HCC patients had lower levels of serum albumin, but higher values of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, bilirubin and alpha-foetoprotein than those of chronic carriers (P<0.001 for all comparisons). The presence of genotype C, higher frequencies of PC A1896 mutants, BCP T1762/A1764 mutants and higher circulating levels of HBV DNA were more frequently detected in HCC patients than that in chronic carriers (P<0.001 for all observations). Logistic regression analysis revealed that BCP T1762/A1764 mutants [odds ratio (OR) 11.14, 95% confidence interval (CI) 3.05-40.72; P<0.001] and PC A1896 mutants (OR 3.75, 95% CI 1.14-12.34; P<0.05) were significantly associated with HCC development.


CONCLUSIONS
Our results indicate that the presence of BCP and PC mutations significantly increases the risk for HCC in chronic hepatitis B patients. These mutations were less often detected in chronic carriers who seldom develop HCC.
Tong
Myron J
MJ
The Liver Center, Huntington Medical Research Institutes, Pasadena, CA 91105, USA. myrontong@hmri.org
Blatt
Lawrence M
LM
Kao
Jia-Horng
JH
Cheng
Jason Tzuying
JT
Corey
William G
WG
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006514:Hepatitis B Surface Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology / Q000821:virology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D015995:Prevalence; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors
D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens