乙型肝炎病毒感染相关疾病中病毒基因型和亚型的分布及其与临床指标的关系

Distribution of HBV genotypes and subgenotypes in patients with chronic hepatitis B,hepatocellular carcinoma,asymptomatic HBV carriers and its clinical relevance

目的:明确乙型肝炎病毒(HBV)基因型及亚型在上海及周边地区HBV感染相关的肝细胞癌、慢性乙型肝炎和HBV携带者中的分布,探讨不同基因型及亚型在HBV相关疾病发展进程中的作用。方法:通过多重PCR对462例肝细胞癌患者(HCC组)、234例慢性乙型肝炎患者(CHB组)和110例HBV病毒携带者(ASC组)进行HBV基因型及亚型的鉴定。结果:与CHB组相比,HCC组C型比例增高(P=0.009),B型比例下降(P=0.045),可见少量A、D型;基因型B均为B2亚型;基因型C以C2亚型为主(98.5%),可见少量C1亚型(1.5%)。B2和C2型患者中,HCC组比CHB组HBeAg阳性率低(P=0.005,P=0.008),而抗HBe阳性率高(P=0.003,P=0.001)。HCC组内混合型HBeAg阳性率最高,明显高于B2型(P=0.016)。在40～60岁的HCC患者中,HBVDNA载量B2型<C2型<混合型(B2型vsC2型,P=0.029;B2型vs混合型,P=0.021;C2型vs混合型,P=0.041)。结论:上海及周边地区HBV基因亚型以C2型为主,B2型次之,HCC、CHB及ASC人群中的基因型构成不同;混合型感染比单一基因型引起的病毒载量和HBeAg阳性率高,更容易导致HCC的形成。

Objective：To elucidate the distribution of HBV genotypes and subgenotypes in patients with chronic hepatitis B （CHB）, hepatocellular carcinoma（HCC） and asymptomatic HBV carriers（ASC） in Shanghai and areas around Shanghai, and to analyze the role of HBV genotypes and subgenotypes in the carcinogenesis and progress of HBV-related diseases. Methods： The HBV genotypes and subgenotypes were determined in 462 HCC patients, 234 CHB patients and 110 ASCs from Shanghai and areas around Shanghai by a multiplex PCR assay. Results： Genotypes A, B, C and D and subgenotypes B2, C1 and C2 were detected. Genotype C（mainly C2, 98.5% ） and B（B2, 100% ） were more prevalent than other genotypes in our group. Compared with CHB group, HCC group had higher proportion of genotype C（P=0. 009） and lower proportion of genotype B（P=0. 045）. In the patients infected with HBV subgenotypes B2 or C2, the expression of HBeAg in CHB group was significantly higher than that in HCC group（P=0. 005; P=0. 008）, and the expression of anti-HBe was lower in CHB group（P=0. 003,P=0. 001）. In HCC patients, expression of HBeAg in patients infected with mixture genotype was higher than that in those infected with other genotypes（P=0. 016 for B2）. HCC patients （aged from 40 to 60） with HBV B2 infection had lower viral load than those with C2 and genotype mixture（P= 0. 029, P= 0. 021 ） ; and patients with HBV C2 infection had lower viral load than those with genotype mixture（P=0. 041）. Conclusion： Subgenotype C2 is more prevalent than B2 in people living in Shanghai and areas around Shanghai. The compositions of HBV genotypes and subgenotypes are different in patients with CHB, HCC and ASCs. Co-infection with different HBV-genotypes is associated with higher viral load, expression of HBeAg and easier carcinogenesis of HCC.