[Risk features of HBV in human hepatocarcinogenesis: a nested case-controlled study].
OBJECTIVE
To identify the association strength of the prevalence of HBeAg, covalently closed circular DNA (cccDNA) and 1762/1764 nucleotide mutations of hepatitis B virus (HBV) with the occurrence of hepatocellular carcinoma (HCC) in Qidong high risk male cohort.


METHODS
A cohort of 377 middle aged HBV infected men in Qidong was followed from January 1989 to December 2002. Incident HCC cases were carefully registered. A matched case-controlled study was conducted on 32 pairs of inherent HCC cases with their matched non-HCC controls. Serum HBeAg was measured by ELISA. cccDNA was detected by primer selected PCR. 1762/1764 nucleotide mutations of HBV was identified by PCR of X gene segment spanning the mutation region. Standard statistical comparison between the prevalence of each HBV marker in HCC versus in control group provided the odds ratio with P value to evaluate its association strength with HCC occurrence.


RESULTS
Serum HBeAg prevalence was 53.1% (17/32) in HCC group versus and 15.6% (5/32) in controls (OR = 6.12, P < 0.01). Prevalence of serum cccDNA was detected in 62.5% (21/32) of HCC cases but in 25.0% (8/32) of controls (OR = 5.73, P < 0.01). Sequence of detected cccDNA was repeatedly found to be over 90% homologous with HBV. However, the mutation rate of nucleotide 1762/1764 was not found to be statistically higher in the HCC group versus its controls (OR = 1.54, P = 0.425).


CONCLUSIONS
The Qidong male case-controlled cohort had shown that serum HBeAg and cccDNA prevalence were tightly associated with hepatocellular carcinoma occurrence in HBV infected men. These biomarkers may have predictive value in earlier diagnosis and therapeutic effect monitoring.
Zhang
Feng
F
Hepatic Surgery Centre, Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Shao
Yong-fu
YF
Gao
Ji-dong
JD
Xu
Yang
Y
Liu
Guo-ting
GT
Xu
Li-bin
LB
Wu
Zhi-yuan
ZY
Gao
Wen-hong
WH
Sun
Zong-tang
ZT
D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000821:virology*; D016022:Case-Control Studies; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000097:blood / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000821:virology*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011446:Prospective Studies; D012307:Risk Factors
D004279:DNA, Viral; D006513:Hepatitis B e Antigens