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*

doi:10.3969/j.issn.1672-5069.2016.05.005

摘要/Abstract

摘要： 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。

关键词: 乙型肝炎, HBV基因亚型, 直接测序法, 进化树

Abstract: 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.

Key words: Hepatitis B, HBV Subgenotypes, Sequence analysis, Phylogenetic tree

邓浩辉, 许敏, 高洪波, 关玉娟. 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^*[J]. 实用肝脏病杂志, 2016, 19(5): 528-531.

Deng Haohui, Xu Min, Gao Hongbo, et al.. Hepatitis B virus subgenotypes in 424 patients with hepatitis B,hepatic failure, liver cirrhosis and hepatocellular carcinoma in Guangzhou[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2016, 19(5): 528-531.

参考文献

[1] 中华医学会肝病学分会和感染病学分会.慢性乙型肝炎防治指南（2015年版）. 实用肝脏病杂志,2016,19（3）：Ⅴ-ⅩⅩⅢ.
[2] 中华医学会感染病学分会肝衰竭与人工肝学组和肝病学分会重型肝病与人工肝学组. 肝衰竭诊治指南.实用肝脏病杂志,2013,16（3）：210-216.
[3] 中华人民共和国卫生部. 原发性肝癌诊疗规范（2011年版）. 临床肿瘤学杂志,2011,16（10）：929-946.
[4] Tran TT,Trinh TN,Abe K. New complex recombinant genotype of hepatitis B virus identified in Vietnam. J Virol,2008,82（11）:5657-5663.
[5] Olinger CM,Jutavijittum P,Hubschen JM,et al. Possible new hepatitis B virus genotype,southeast Asia. Emerg Infect Dis,2008,14（11）:1777-1780.
[6] Tatematsu K,Tanaka Y,Kurbanov F,et al. A genetic variant of hepatitis B virus divergent from known human and ape genotypes isolated from a Japanese patient and provisionally assigned to new genotype J. J Virol,2009,83（20）:10538-10547.
[7] 黄月华,梁敏锋,杨海红,等. 广东地区乙型肝炎病毒C基因亚型的分布与临床. 广东医学,2008,29（12）：2000-2002.
[8] 肖蕾,王雪刚,曾国兵,等. 中国广东地区乙型肝炎病毒基因亚型的分布. 肝脏,2006,11（3）：149-151.
[9] Kramvis A. The clinical implications of hepatitis B virus genotypes and HBeAg in pediatrics. Rev Med Virol,2016,[Epub ahead of print].
[10] Mulyanto,Depamede SN,Surayah K,et al. Identification and characterization of novel hepatitis B virus subgenotype C10 in Nusa Tenggara, Indonesia. Arch Virol,2010,155（5）:705-715.
[11] Mulyanto,Depamede SN,Surayah K,et al. A nationwide molecular epidemiological study on hepatitis B virus in Indonesia:identification of two novel subgenotypes,B8 and C7. Arch Virol,2009,154（7）:1047-1059.
[12] Mulyanto H,Depamede SN,Wahyono A,et al. Analysis of the full-length genomes of novel hepatitis B virus subgenotypes C11 and C12 in Papua,Indonesia. J Med Virol,2011,83（1）:54-64.
[13] Mulyanto M,Pancawardani P,Depamede SN,et al. Identification of four novel subgenotypes（C13-C16） and two inter-genotypic recombinants（C12/G and C13/B3） of hepatitis B virus in Papua province,Indonesia. Virus Res,2012,163（1）:129-140.
[14] Yano Y,Utsumi T,Lusida MI,et al. Hepatitis B virus infection in Indonesia. World J Gastroenterol,2015,21（38）:10714-10720.
[15] Sakamoto T,Tanaka Y,Orito E,et al. Novel subtypes （subgenotypes） of hepatitis B virus genotypes B and C among chronic liver disease patients in the Philippines. J Gen Virol,2006,87（Pt 7）:1873-1882.
[16] Cavinta L,Sun J,May A,et al. A new isolate of hepatitis B virus from the Philippines possibly representing a new subgenotype C6. J Med Virol,2009,81（6）:983-987.
[17] Shi W,Zhu C,Zheng W,et al. Subgenotyping of genotype C hepatitis B virus:correcting misclassifications and identifying a novel subgenotype. PLoS One,2012,7（10）:e47271.
[18] 张爱民,王慧芬,王海滨,等. 中国30个地区HBV基因型分布特点和临床意义. 中华实验和临床病毒学杂志,2011,25（2）： 126-128.
[19] 曾华,张智贤,梁倩文,等. 乙型肝炎病毒 B、C 基因型与临床表现. 广州医科大学学报,2015,25（2）：58-60.
[20] 黄月华,周彬,王战会,等. 中国乙型肝炎病毒B基因亚型的分布. 中华实验和临床病毒学杂志,2007,21（2）：111-113.
[21] Wai CT,Fontana RJ,Polson J,et al. Clinical outcome and virological characteristics of hepatitis B-related acute liver failure in the United States. J Viral Hepat 2005,12（2）:192-198.
[22] Yu MW,Yeh SH,Chen PJ,et al. Hepatitis B virus genotype and DNA level and hepatocellular carcinoma:a prospective study in men. J Natl Cancer Inst,2005,97（4）:265-272.
[23] 谢巧灵,丛庆伟,吴凌虹,等. 耐核苷（酸）类药物慢性乙型肝炎和肝硬化患者血清HBV基因型和P区耐药突变位点分析. 实用肝脏病杂志,2016,19（1）：60-63.

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^*

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

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	朱凌云, 张茂海, 崔莎莎, 张秋萍. 慢性乙型肝炎患者血清IL-12、IL-18水平和外周血单个核细胞FOXp3基因水平研究^*[J]. 实用肝脏病杂志, 2019, 22(6): 816-819.
[2]	石莹莹, 王元喜. 替比夫定联合阿德福韦酯治疗慢性乙型肝炎患者效果及其对肾功能的影响^*[J]. 实用肝脏病杂志, 2019, 22(6): 820-823.
[3]	闵峰, 黄文琪, 吴卫兵, 张丽, 范荣华. 慢性乙型肝炎患者血清脂肪细胞因子水平变化及其临床意义^*[J]. 实用肝脏病杂志, 2019, 22(6): 824-827.
[4]	张迎明, 申爽, 田飞, 孙园园. IFNL4和IL-28B基因多态性检测评估慢性乙型肝炎患者抗病毒治疗应答价值分析^*[J]. 实用肝脏病杂志, 2019, 22(6): 828-831.
[5]	吴海义, 陈建新. 四种诊断模型诊断乙型肝炎病毒携带者肝纤维化的效能分析^*[J]. 实用肝脏病杂志, 2019, 22(6): 832-835.
[6]	马丽英, 沈利娟. 妊娠后期应用替诺福韦治疗血清HBV高载量孕妇阻断HBV母婴传播的疗效及安全性分析^*[J]. 实用肝脏病杂志, 2019, 22(6): 836-839.
[7]	李传杰, 徐静, 王亮亮, 潘劲劲, 刘波. 恩替卡韦治疗慢性乙型肝炎患者血清HBsAg变化与病毒学应答的相关性研究[J]. 实用肝脏病杂志, 2019, 22(6): 928-929.
[8]	杜科业, 杨东亮, 刘嘉. 慢性乙型肝炎与调节性T细胞研究进展^*[J]. 实用肝脏病杂志, 2019, 22(5): 613-616.
[9]	廖桂婵, 彭颉, 张小勇. 肝细胞介导的天然免疫应答参与控制乙型肝炎病毒感染^*[J]. 实用肝脏病杂志, 2019, 22(5): 617-619.
[10]	赵协山, 伍春瑢, 王春峰, 余积洁, 何青. 替诺福韦联合安络化纤丸治疗HBeAg阴性慢性乙型肝炎患者疗效及其血清肝纤维化指标的变化研究*[J]. 实用肝脏病杂志, 2019, 22(5): 644-647.
[11]	涂杰霞, 王安娜, 廖若汐. 干扰素α-2b与聚乙二醇干扰素α-2a治疗慢性乙型肝炎患者疗效比较研究*[J]. 实用肝脏病杂志, 2019, 22(5): 648-651.
[12]	高伟, 侯勇. 肝脏硬度值检测诊断慢性乙型肝炎患者肝组织纤维化的效能分析*[J]. 实用肝脏病杂志, 2019, 22(5): 652-655.
[13]	朱玉成, 闫家微, 孙景坤, 张秋月. 慢加急性肝衰竭患者血清二胺氧化酶水平及其临床意义探讨*[J]. 实用肝脏病杂志, 2019, 22(5): 672-675.
[14]	张梅, 石秀英, 李林娟, 薛亚妮. 肝源性糖尿病患者肝组织干扰素诱导蛋白-10表达变化*[J]. 实用肝脏病杂志, 2019, 22(5): 688-691.
[15]	陈嵘, 黄美玲, 凌雪梅, 林小红, 曾俊, 黎云, 夏建红. 替比夫定联合HBIG和乙肝疫苗阻断HBV母婴传播临床效果分析*[J]. 实用肝脏病杂志, 2019, 22(5): 752-753.