乙型肝炎病毒S基因变异与乙型肝炎病毒相关慢加急性(亚急性)肝衰竭的关系探讨  

The relationship between hepatitis B virus S gene mutations and hepatitis B virus-related acute on chronic liver failure

作　　者：邓浩辉 许敏 高洪波 Deng Haohui;Xu min;Gao Hongbo(Department of Infectious Diseases, Guangzhou Eighth People′s Hospital, Guangzhou Medical University, Guangzhou 510060, China)

机构地区：[1]广州医科大学附属市八人民医院重症肝病科,510060

出　　处：《中华传染病杂志》2019年第1期16-20,共5页Chinese Journal of Infectious Diseases

基　　金：广东省科技计划项目(2015B020226004);广州市医药卫生科技项目(20171A011264).

摘　　要：目的探讨HBV S基因序列变异与HBV相关慢加急性(亚急性)肝衰竭(HBV-related acute on chronic liver failure,HBV-ACLF)的关系。方法纳入2012年7月至2017年9月广州市第八人民医院门诊或住院的非活动性HBsAg携带者51例(携带组)、CHB患者78例(CHB组)、HBV-ACLF患者101例(HBV-ACLF组)、HBV相关肝硬化(liver cirrhosis,LC)患者69例(LC组)和HBV相关肝细胞癌(hepatocellular carcinoma,HCC)患者78例(HCC组)。采用套式PCR扩增HBV全基因组和S基因片段,直接测序法检测HBV变异位点,使用Mega 7.0软件Neighbor-joining法构建基于S基因的进化树进行基因分型,使用Geneious R10.0.5软件对S抗原的读码框进行翻译,确定非同义突变和同义突变的变异位点。组间比较采用χ^2检验、Fisher确切概率法,相关性采用logistic回归分析。结果在HBV-ACLF组、CHB组、携带组、LC组和HCC组中,HBV B基因型患者分别为83、51、34、31和35例,HBV C基因型患者分别为18、27、17、38和43例。在HBV B基因型患者中,HBV全基因组差异显著的变异位点有:S基因(T216C、G285A和A529G),增强子Ⅰ(A1317G),基本核心启动子区(A1762T/G1764A),前C/C区(A1846T、C1913A、G1896A、T2045A、C2078G和C2304A);在HBV C基因型患者中,未发现差异显著的变异位点。HBV B基因型的患者中,T216C(sL21S)变异在HBV-ACLF组显著高于携带组、CHB组和HCC组(χ^2值分别为14.474、10.982和5.440,均P<0.05),但与LC组比较差异无统计学意义(χ^2=2.641,P=0.106);G285A(sG44E)变异在HBV-ACLF组显著高于携带组、CHB组、LC组和HCC组(χ^2值分别为27.301、29.287、15.719和16.076,均P<0.01)。在HBV C基因型的患者中,HBV S基因高频变异在各组患者中均差异无统计学意义(均P>0.05)。logistic回归分析提示男性(OR=6.90,95%CI:1.52~24.39,P=0.010)、HBeAg阴性(OR=4.73,95%CI:1.60~13.94,P=0.005)、B基因型(OR=4.80,95%CI:1.82~12.16,P=0.006)和G285A变异(OR=7.72,95%CI:5.64~16.37,P=0.006)是HBV-ACLF发生的独立危险因素。结论HBV S�Objective To investigate and analyze the relationship between hepatitis B virus (HBV) S gene mutations and the occurrence of HBV-related acute on chronic liver failure (HBV-ACLF). Methods A total of 377 patients were enrolled in this study, including 51 inactive hepatitis B surface antigen (HBsAg) carriers, 78 chronic hepatitis B (CHB) patients, 101 HBV-ACLF patients, 69 HBV-related liver cirrhosis (LC) patients and 78 HBV-related hepatocellular carcinoma (HCC) patients. Serum samples were collected from July 2012 to September 2017 in Guangzhou Eighth People′s Hospital. Nested polyoneras chain reaction (PCR) was performed for all the samples, the HBV whole genome and HBV S gene were amplified. PCR products were sequenced by Sanger sequencing method. HBV genotypes were determined by the phylogenetic tree based on HBV S gene constructed by Mega 7.0 software with the neighbor-joining method. Geneious R10.0.5 software was used to analyze the mutations of the HBV genome. The data in different groups were compared by χ^2 test or Fisher′s exact test. The correlation analysis was done by logistic regression. Results Among the 377 patients enrolled in this study, the HBV-ACLF, CHB, inactive HBsAg carriers, and HCC patients infected with HBV genotype B were 83, 51, 34, 31, and 35 cases respectively, and the patients infected with HBV genotype C were 18, 27, 17, 38, and 43 cases respectively. The results of this study showed that 11 mutations were significantly higher in HBV-ACLF patients than CHB patients who were infected with HBV genotype B, including T216C, G285A and A529G in HBV S gene, A1317G in HBV enchanter I, A1762T/G1764A in basal core promoter (BCP) gene, A1846T, C1913A, G1896A, T2045A, C2078G, C2304A in HBV preC/C gene. However, no significant difference mutations were found in HBV-ACLF patients and CHB patients who were infected with HBV genotype C. In the patients infected with HBV genotype B, the prevalence of T216C (sL21S) mutation in HBV-ACLF was significantly higher than those in inactive HBsAg carrie

关 键 词：肝炎病毒 乙型 突变 慢加急性肝衰竭 

分 类 号：R512.62[医药卫生—内科学]