广州地区424例乙型肝炎患者病毒基因亚型分布与乙型肝炎疾病谱的关系探讨*

目的调查广州地区乙型肝炎病毒（HBV）基因亚型分布情况, 并探讨其与HBV感染疾病谱的关系。方法采用直接测序法测定S基因序列并构建基于S基因进化树,对424例HBV感染者进行研究,随机选择慢性乙型肝炎（CHB）137例,HBV相关慢加急性肝衰竭（HB-ACLF）90例,肝硬化（LC）90例和肝细胞癌（HCC）107例,应用SPSS 13.0软件进行x²检验、方差分析和多元Logistic回归分析。结果在424例HBV感染者中,B2亚型 269例（63.44%）,C1亚型117例（27.59%）,C2亚型36例（8.49%）,C5亚型 2例（0.47%）,未发现其他亚型;CHB患者感染HBV B2亚型、C1亚型、C2亚型和C5亚型分别为70.1%、24.09%、5.11%和0.73%;HB-ACLF患者感染HBV B2亚型、C1亚型和C2亚型分别为87.78%、7.78%、4.44%,其中HBV B2基因亚型显著高于CHB（x²=9.641,P=0.002）、LC（x²=19.565,P=0.000）、HCC患者（x²=26.789,P=0.000）;LC患者感染HBV B2亚型、C1亚型和C2亚型分别为50.00%、36.67%、13.33%,其中HBV C1和C2亚型显著高于CHB患者（x²=6.262,P=0.012;x²=4.790,P=0.029）或HB-ACLF患者（x²=25.894,P=0.000;x²=4.390,P=0.036）;HCC患者感染HBV B2亚型、C1亚型、C2亚型和C5亚型分别为45.79%、41.12%、12.15%、0.93%,其中HBV C1和C2亚型也显著高于CHB患者（x²=11.264,P=0.001;x²=3.957,P=0.047）或HB-ACLF患者（x²=28.327,P=0.000;x²=3.904,P=0.048）;LC和HCC患者HBV C1和C2基因亚型无明显差异（x²=0.429,P=0.512;x²=0.804,P=0.833）;多因素Logistic回归分析提示B2亚型是HB-ACLF发生的危险因素（OR=2.597,95%CI=1.145~5.891,P=0.022）,C型是HCC发生的危险因素（OR=3.257,95%CI=1.49~7.194,P=0.003）。结论广州地区HBV基因亚型主要由B2、C1和C2亚型构成,同时也存在C5亚型;广州地区B2亚型感染者可能更易发生HBV相关慢加急性肝衰竭,而C1和C2亚型感染者可能更易进展为肝硬化和肝细胞癌。

Hepatitis B virus subgenotypes in 424 patients with hepatitis B,hepatic failure,liver cirrhosis and hepatocellular carcinoma in Guangzhou

Objective To investigate hepatitis B virus （HBV） subgenotypes distribution and its implication in patients with chronic hepatitis B in Guangzhou. Methods 424 patients were enrolled in this study,including 137 with chronic hepatitis B（CHB）,90 with HBV-related acute-on-chronic liver failure （HB-ACLF）,90 with 1iver cirrhosis（LC） and 107 with hepatocellular carcinoma（HCC）. HBV subgenotypes were determined by direct sequencing of HBV S gene and the phylogenetic tree was constructed. The data was compared by x² test,one way ANOVA and Logistic regression analysis. Results Out of 424 patients with HBV infection, 269（63.44%） were infected with HBV B2,117 （27.59% with HBV C1,36 （8.49%） with HBV C2 and 2 （0.47%） with C5; the HBV B2,C1,C2 and C5 Infection in patients with CHB were 70.1%,24.09%,5.11%,0.73%;the HBV B2,C1 and C2 in patients with HB-ACLF were 87.78%,7.78%,4.44%,with HBV B2 subgenotpe significantly higher than in patients with CHB（x²=9.641,P=0.002）,with LC（x²=19.565,P=0.000） or with HCC（x²=26.789,P=0.000）;the subgenotypes of HBV B2,C1 and C2 in patients with LC were 50.00%,36.67%,13.33%,with HBV C1 and C2 subgenotpes significantly higher than in patients with CHB（x²=6.262,P=0.012,x²=4.790,P=0.029） or in patients with HB-ACLF（x²=25.894 P=0.000,x²=4.390,P=0.036）;the subgenotypes of HBV B2,C1,C2 and C5 in HCC patients were 45.79%,41.12%,12.15%,0.93,with HBV C1 and C2 subgenotypes significantly higher than in patients with CHB（x²=11.264,P=0.001,x²=3.957,P=0.047） or in patients with HB-ACLF（x²=28.327,P=0.000,x²=3.904,P=0.048）;there was no significant difference between HCC patients with HBV C1 and C2 subgenotype infection and LC patients;Logistic regression analysis showed that HBV B2 subgenotype was the independent risk factor for HB-ACLF occurrence, and HBV C genotype was the independent risk factor for HCC occurrence. Conclusion HBV B2,C1,C2 are the most frequent HBV subgenotypes in Guangzhou. The HBV B2 subgenotpe is prevalent in patients with HB-ACLF and HBV C1 and C2 is frequent in patients with LC and HCC.