乙肝病毒活跃复制与肝细胞癌发生的相关性研究

目的 前瞻性队列研究启东肝癌高发区人群HBV HBeAg、cccDNA的表达与肝细胞癌发生的相关性。方法 对1989--2002年启东地区377例HBV感染的男性患者进行随访，采集系列血清，监测肝细胞癌的发生，选取其中发生肝癌的32例患者与32例非肝癌慢性HBV患者作对照，组成巢式病例对照研究队列。采用ELISA法检测血清HBeAg，半巢式PCR扩增HBV cccDNA并经序列测定证实。结果 血清HBeAg在肝癌组和对照组的阳性率分别是53．1％和15．6％（OR=6．12，P＜0．01）。HBV cccDNA，在肝癌组和对照组的阳性率分别是62．5％和21．8％（OR=5．73，P〈0．01）。结论 慢性HBV感染的中年男性，HBeAg和ccc DNA反映的HBV复制的活跃程度与肝癌的发生密切关联，可作为预测肝癌发生的风险指标。

The relationship between HBV replicative markers and hepatocarcinogenesis

Objective To identify the association strength of the prevalence of HBeAg, cccDNA with the occurrence of HBV related hepatocellular carcinoma (HCC) in high risk male cohort in Qidong area in China. Methods A cohort of 377 middle aged HBV infected men in Qidong was followed from 1989 for 13. 25 years. HCC cases were registered. A matched case-controlled study was conducted on 32 pairs of inherent HCC cases with non-HCC controls. Serum HBeAg was measured by ELISA. cccDNA was detected by semi-nested PCR and verified by DNA sequencing. Standard statistical comparison between the prevalence of each HBV marker in HCC versus control group provided the odds ratio and P-value was used to evaluate its association strength with HCC occurrence. Results Serum HBeAg prevalence was 53. 1% (17/32) in HCC group versus 15. 6% (5/32) in controls, odds ratio (OR) =6. 12, P <0. 01. Prevalence of serum cccDNA was detected in 62. 5% (21/32) of HCC cases and in 21. 8% (8/32) of controls, with OR of 5. 73 and P <0. 01. Sequence of detected cccDNA was, found to be over 90% homologous with HBV. Conclusions A case-controlled study in this cohort showed that serum HBeAg and cccDNA prevalence were highly associated with hepatocellular carcinoma occurrence in HBV infected men. These viral markers may be of predictive value for early HCC diagnosis.