OBJECTIVETo 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.

METHODSA 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.

RESULTSSerum 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).

CONCLUSIONSThe 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.