贵州省四城市乙型肝炎病毒感染者病毒基因型调查研究

Investigation on virus genotype in patients infected with hepatitis B virus in four cities of Guizhou

目的调查贵州省4城市乙型肝炎病毒(HBV)感染者的病毒基因型及其与临床的关系。方法选择贵阳、遵义、凯里、都匀4城市慢性HBV感染患者共786例,其中无症状携带者(ASC)346例,慢性肝炎(CH)313例,肝硬化(LC)77例,肝细胞肝癌(HCC)50例。用S基因限制性片段长度多态性确定基因型,直接测序分析B基因亚型,比较主要基因型地区分布及临床特征。结果786例中,B基因型497例(63．23%),C型275例(34．99%),A型7例(0．89%),D型7例(0．89%),未发现E、F型。B型的分布：凯里市最高(96．04%),遵义、都匀市其次(78．79%、64．52%),贵阳市最低(53．14%)。C型的分布,贵阳(45．84%)高于都匀(34．41%)、遵义(13．13%)及凯里市(3．96%),差异有统计学意义(P＜0．05或P＜0．01)。94例B型感染者中,93例为Ba(98．94%)、1例为Bj亚型。从ASC、CH、LC到HCC组,B型的分布逐渐降低,而C型在各组的分布逐渐增高。与B型相比,C型感染者年龄较大；ALT水平较高(P＜0．05)；HBeAg阳性较低(P＜0．025)。结论贵州省存在A、B、C、D 4种HBV基因型,但以B型为主,C型其次,A、D型极少。B型中又以Ba亚型为主。B、C基因型在贵州省4城市的分布有一定差异。

Objective To investigate the distribution of hepatitis B virus （HBV） genotype in Guizhou and to study the relationship between the genotype and the progression of liver disease. Methods 786 patients with chronic HBV infection, from 4 cities of Guizhou, including 346 asymptomatic carriers （ASC）, 313 chronic hepatitis （CH）, 77 liver cirrhosis （LC）, 50 hepatocellular carcinoma （HCC） were examined. HBV genotype was determined by restriction fragment length polymorphism analysis and the subtypes were determined by direct sequencing of PCR product in 94 patients with HBV B genotype, the relationship between HBV genotype and the progression of liver disease was studied by multifactor analysis such as HBeAg positivity,HBV DNA load and ALT level. Results Of the 786 patients, 7（0.89 % ）, 497 （63.23 % ）, 275 （34.99 % ）, and 7 （0.89 % ） belonged to genotype A, B, C, D, respectively. There was statistically significant difference in the distribution of genotype B among Kaili （96.04%）, Zunyi （78.79 % ）, Duyun （ 64.52 % ） and Guiyang （ 53.14 % ） （ P 〈 0.01 ）. Genotype C was more prevaient in Guiyang than in other three cities （P〈 0.01, or P 〈 0.05）. Out of 94 genotypes B, 93 （98.94%） belonged to subtype Ba, only one was subtype Bj. There were statistically significant difference in the distribution of genotype B and C among various stage of liver disease （P 〈 0.05 or P 〈 0.01 ）. Genotype B showed a gradual decrease from ASC, CH, LC to the HCC group while in contrast, genotype C showed a gradual increase in the same order. The ALT levels and the mean age were significantly higher and older in patients with genotype C than those in genotype B （P〈 0.01 or 0.05）. The HBeAg positivity was significantly lower in genotype C than that in genotype B （P〈 0.025）. Conclusion Data showed that there were genotype A,B,C and D existing in Guizhou. Genotype B was the major one but genotype C was more commonly seen. In genotype B, subtype Ba appeared to be predominant. The geographic distribution of genotype B and C were different in some cities of Guizhou. Compared to genotype B, genotype C was associated with the development of more severe liver damage.