Precore/basal core promoter mutants and hepatitis B viral DNA levels as predictors for liver deaths and hepatocellular carcinoma.
OBJECTIVE
To conduct a retrospective study in 400 chronic hepatitis B patients in order to identify hepatitis B viral factors associated with complications of liver disease or development of hepatocellular carcinoma.


METHODS
The mean follow-up time was 83.6+/-39.6 mo. Alpha-fetoprotein test and abdominal ultrasound were used for cancer surveillance. Hepatitis B basal core promoter mutants, precore mutants, genotypes, hepatitis B viral DNA (HBV DNA) level and hepatitis B e antigen (HBeAg) were measured. Univariate analysis and logistic regression were used to assess odds ratios for viral factors related to liver deaths and hepatocellular carcinoma development.


RESULTS
During follow-up, 38 patients had liver deaths not related to hepatocellular carcinoma. On multivariate analysis, older age [odds ratio: 95.74 (12.13-891.31); P<0.0001], male sex [odds ratio: 7.61 (2.20-47.95); P=0.006], and higher log10 HBV DNA [odds ratio: 4.69 (1.16-20.43); P<0.0001] were independently predictive for these liver related deaths. Also, 31 patients developed hepatocellular carcinoma. Multivariate analysis showed that older age [odds ratio: 26.51 (2.36-381.47); P=0.007], presence of precore mutants [odds ratio: 4.23 (1.53-19.58); P=0.02] and presence of basal core promoter mutants [odds ratio: 2.93 (1.24-7.57); P=0.02] were independent predictors for progression to hepatocellular carcinoma.


CONCLUSIONS
Our results show that high levels of baseline serum HBV DNA are associated with non-hepatocellular carcinoma-related deaths of liver failure, while genetic mutations in the basal core promoter and precore regions are predictive for development of hepatocellular carcinoma.
Tong
Myron J
MJ
Liver Center, Huntington Medical Research Institutes, 660 South Fair Oaks Avenue, Pasadena, California 91105, United States. myrontong@hmri.org
Blatt
Lawrence M
LM
Kao
Jia-Horng
JH
Cheng
Jason Tzuying
JT
Corey
William G
WG
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000821:virology*; D004279:DNA, Viral / Q000097:blood / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006509:Hepatitis B / Q000150:complications; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D017093:Liver Failure / Q000097:blood / Q000401:mortality* / Q000821:virology*; D008113:Liver Neoplasms / Q000097:blood / Q000821:virology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies
D004279:DNA, Viral; D006513:Hepatitis B e Antigens