乙型肝炎病毒感染者病毒基因型和亚型分布及其临床意义

Distribution and clinical significance of hepatitis B virus (HBV) genotypes and subtypes in HBV-infected patients

目的研究不同类型乙型肝炎病毒(HBV)感染者中HBV基因型和亚型分布情况及其临床意义。方法应用基因型和亚型特异性引物聚合酶链反应法(PCR),对北京、长春、汉川、深圳、清远和南京等6个城市445份HBV感染者血清进行基因型及亚型分型,其中急性肝炎7例,无症状携带者36例,慢性乙型肝炎352例,肝硬化28例,肝细胞癌22例。通过对PCR产物测序确定其基因型,以验证该法的准确性。结果445份血清中,239例(53.7%)为C型,其中13例(5.4%)为C1亚型,135例(56.5%)为C2亚型,91例(38.1%)为非C1/C2亚型;145例(32.6%)B型,其中100例(69.0%)为Ba亚型,25例(17.2%)为Bj亚型,20例(13.8%)为非Ba/Bj亚型;61例(13.7%)为B型与C型混合感染,其中6例(9.8%)为Ba与C1 亚型混合感染,3例(4.9%)为Bj与C1亚型混合感染,15例(24.6%)为Ba与C2亚型混合感染,8例(13.1%) 为Bj与C2型混合感染,11例(18.0%)为Ba与非C1/C2亚型混合感染,7例(11.5%)为Bj与非C1/C2亚型混合感染,2例(3.3%)为非Ba/Bj亚型与C1亚型混合感染,3例(4.9%)为非Ba/Bj亚型与C2亚型混合感染,6 例(9.8%)为非Ba/Bj亚型与非C1/C2亚型混合感染。未检测到其他基因型及亚型。在不同类型乙型肝炎病毒感染者中,B型、C型、B与C型混合感染及亚型分布差异有统计学意义,在肝硬化和肝细胞癌患者中C型所占比例较高(分别为78.6%和86.4%),无症状携带者中B型所占比例较高(72.2%)。但不同性别患者中,HBV 基因型和亚型分布无差异。在HBeAg阳性和阴性感染者中,HBV基因型和亚型分布差异也有统计学意义。结论该6个城市HBV感染者中,以B2和C2亚型占优势,C基因型可能与肝硬化和肝细胞癌的发生有关。

Objective To study hepatitis B virus （HBV） genotype and subtype distribution and its clinical significance in HBV-infected patients. Methods We used type/subtype-specific primers and PCR to detect HBV genotype and subtype of 445 HBV-infected patients from Beijing, Changchun, Hanchuan Shenzhen, Qingyuan and Nanjing, including 7 acute hepatitis （AH）, 36 asymptomatic HBV carriers （ASC）, 352 chronic hepatitis （CH）, 28 liver cirrhosis （LC）, and 22 hepatocellular carcinoma （HCC） cases. Genotyping results were confirmed by PCR product sequencing. Results Among 445 HBV-infected patients, the proportions of genotype B, C, and B/C were 32.6% （145/445）, 53.7% （239/445）, and 13.7% （61/445）, respectively. In genotype C, 13 （5.4%） were subtype C1, 135 （56.5%） were subtype C2, and the remaining 91 （38.1%） were neither C1 nor C2. In genotype B, 100 （69.0%） were subtype Ba, 25 （17.2%） subtype Bj, and the other 20 （13.8%） were neither Ba nor Bj. In genotype B/C, 15 （24.6%） were Ba/C2, 8 （13.1%） Bj/C2, 6 （9.8%） Ba/C1, 3 （4.9%） Bj/C1, 11 （18.0%） Ba/neither C1 nor C2, 7 （11.5%） Bj/neither C1 nor C2, and 6 （9.8%） neither Ba nor Bj/neither C1 nor C2, 2（3.3%） neither Ba nor Bj/CI, 3 （4.9%） neither Ba nor Bj/C2. The HBV genotype and subtype distribution we found exhibited significant differences in the various clinical types of HBV infection tested, and showed that genotype C was predominant among patients with liver cirrhosis （78.6%） and hepatocellular carcinoma （86.4%） while genotype B was predominant in asymptomatic carriers （72.2%）. In addition, genotype and subtype distribution showed no significant differences between male and female patients, but genotype and subtype distribution showed significant differences in patients positive or negative with HBeAg. Coneluslon Subtypes Ba and C2 are predominant in patients with hepatitis B from these 6 cities, and genotype C may be associated with the development of liver cirrhosis and hepatocellular carcinoma.