39例成人急性乙型肝炎患者血清HBV基因变异检测及其临床意义探讨*

doi:10.3969/j.issn.1672-5069.2016.05.004

实用肝脏病杂志 ›› 2016, Vol. 19 ›› Issue (5): 524-527.doi: 10.3969/j.issn.1672-5069.2016.05.004

39例成人急性乙型肝炎患者血清HBV基因变异检测及其临床意义探讨^*

杜晓菲, 马丽娜, 柳雅立, 魏飞力, 吴云, 陈新月

100069 北京市首都医科大学附属北京佑安医院国际医疗部

收稿日期:2016-04-15 出版日期:2016-09-10 发布日期:2016-10-12
通讯作者: 陈新月,E-mail：chenxydoc@163.com
作者简介:杜晓菲，女，36 岁，硕士研究生，主治医师。主要从事肝病诊疗工作。E-mail：dxiaofei80@sina.com
基金资助:
“十二五”国家科技重大专项（编号：2013ZX1002002-006）; 首都临床特色应用研究与成果推广项目（编号：Z151100004015181）; 北京市卫生和计划生育委员会科技成果和适宜技术推广项目（标号：TG-2015-020）

Hepatitis B viral genotypes and gene mutations in 39 adult patients with acute hepatitis B

Du Xiaofei, Ma Lina, Liu Yali et al.

Department of International Medical Service,You’an Hospital,Capital Medical University,Beijing 100069,China

Received:2016-04-15 Online:2016-09-10 Published:2016-10-12

摘要/Abstract

摘要： 目的了解成人急性乙型肝炎患者流行的病毒基因型及基因变异情况。方法在2010年12月~2014年1月北京佑安医院收治39例急性乙型肝炎患者,采用直接基因测序法和平行等位基因特异性检测技术检测HBV基因型、P区、S区、前C区（PreC）和基本核心启动子（BCP）区序列。结果在39例患者中,成功测序35例。35例急性乙型肝炎患者感染HBV B基因型12例（36.4%）,C基因型21例（57.6%,D基因型2例（6.0%）;通过直接测序法和PASS法均检测到同1例患者存在A181S耐药变异,变异病毒占准种池比例达100%;直接测序法检测到1例患者存在S区S132F和W172C变异;1例患者存在PreC/BCP 区G1896A和T1758C变异。结论急性乙型肝炎患者感染病毒基因型与文献报道的慢性乙型肝炎患者感染病毒基因型分布一致,以C型和B型为主,存在P区、S区和PreC/BCP区变异可能,未见不同病毒株感染引起转归的不同。

关键词: 急性乙型肝炎, 基因型, 变异

Abstract: Objective To investigate the prevalent viral genotypes and possible gene mutation in adults with acute hepatitis B（AHB）. Methods Serum samples of 39 patients with AHB admitted in our hospital were collected between December 2012 and January 2014. Viral genotypes and sequences of P region,S region,Pre C region and basic core promoter（BCP） were detected by direct sequencing and parallel allele specific sequencing （PASS）. Results 35 out of 39 patients with AHB were sequenced successfully. Genotype distribution in these 35 cases was as follows. Genotype B accounted for 36.4% （12/35）,genotype C for 57.6% （21/35）,and genotype D for 6.0%（2/35）;A181S drug resistance mutation was found in one patient by both sequencing methods,while S132F and W172C mutations in S region as well as G1896A and T1758C mutations in PreC/BCP regions were noticed by direct sequencing in two different cases,respectively. Conclusions Viral genotype distribution of common genotype C and B in patients with AHB is not different in patients with CHB. Patients infected with P region,S region or PreC/BCP region mutants might have similar prognosis as patients infected with wild HBV.

Key words: Acute hepatitis B, Genotype, Mutation

杜晓菲, 马丽娜, 柳雅立, 魏飞力, 吴云, 陈新月. 39例成人急性乙型肝炎患者血清HBV基因变异检测及其临床意义探讨^*[J]. 实用肝脏病杂志, 2016, 19(5): 524-527.

Du Xiaofei, Ma Lina, Liu Yali et al.. Hepatitis B viral genotypes and gene mutations in 39 adult patients with acute hepatitis B[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2016, 19(5): 524-527.

参考文献

[1] GBD 2013 Mortality and Causes of Death Collaborators. Global, regional,and national age-sex specific all-cause and cause-specific mortality for 240 causes of death,1990-2013:a systematic analysis for the Global Burden of Disease Study 2013. Lancet,2015,385：117-171.
[2] Trepo C,Chan HL,Lok A. Hepatitis B virus infection. Lancet,2014,384：2053-2063 .
[3] Xu Z,Liu Y,Xu T,et al. Acute hepatitis B infection associated with drug-resistant hepatitis B virus. J Clin Virol,2010,48:270-274.
[4] Liu Y,Zhong Y,Zou Z,et al. Features and clinical implications of hepatitis B virus genotypes and mutations in basal core promoter/precore region in 507 Chinese patients with acute and chronic hepatitis B. J Clin Virol,2010,47:243-247.
[5] 赵琳,黄玲,王晶慧. 240例初治乙型肝炎患者的流行病学特征. 肝脏,2011,16:442-445.
[6] Thibault V,Aubron-Olivier C,Agut H,et al. Primary infection with a lamivudine-resistant hepatitis B virus. Aids,2002,16:131-133.
[7] 中华医学会传染病与寄生虫病学分会、肝病学分会联合修订. 病毒性肝炎防治方案. 中华肝脏病杂志,2000,8:5-10.
[8] Ozasa A,Tanaka Y,Orito E,et al. Influence of genotypes and precore mutations on fulminant or chronic outcome of acute hepatitis B virus infection. Hepatology,2006,44:326-334.
[9] Matsuura K,Tanaka Y,Hige S,et al. Distribution of hepatitis B virus genotypes among patients with chronic infection in Japan shifting toward an increase of genotype A. J Clin Microbiol,2009,47:1476-1483.
[10] Yotsuyanagi H, Ito K,Yamada N,et al. High levels of hepatitis B virus after the onset of disease lead to chronic infection in patients with acute hepatitis B. Clin Infect Dis,2013,57:935-942.
[11] Yano K,Tamada Y,Yatsuhashi H,et al. Dynamic epidemiology of acute viral hepatitis in Japan. Intervirology,2010,53:70-75.
[12] Ito K,Yotsuyanagi H,Yatsuhashi H,et al. Risk factors for long term persistence of serum hepatitis B surface antigen following acute hepatitis B virus infection in Japanese adults. Hepatology,2014,59:89-97.
[13] Li HM,Wang JQ,Wang R,et al. Hepatitis B virus genotypes and genome characteristics in China. World J Gastroenterol,2015,21（21）:6684-6697.
[14] Chattopadhyay S,Das BC,Hussain Z,et al. Hepatitis B virus genotypes in acute and fulminant hepatitis patients from north India using two different molecular genotyping approaches. Hepatol Res,2006,35:79-82.
[15] Suzuki Y,Kobayashi M,Ikeda K,et al. Persistence of acute infection with hepatitis B virus genotype A and treatment in Japan. J Med Virol,2005,76:33-39.
[16] Hayashi K,Katano Y,Ishigami M,et al. Prevalence and clinical characterization of patients with acute hepatitis B induced by lamivudine resistant strains. J Gastroenterol Hepatol,2010,25:745-749.
[17] Baxa DM,Thekdi AD,Golembieski A,et al. Evaluation of anti-HBV drug resistant mutations among patients with acute symptomatic hepatitis B in the United States. J Hepatol,2013,58:212-216.
[18] Morando F,Rosi S,Fasolato S, et al. Severe acute hepatitis B in a treatment naive patient with antiviral drug resistant mutations in the polymerase gene. J Med Virol,2013,85:210-213.
[19] Clements CJ,Coghlan B,Creati M,et al. Global control of hepatitis B virus:does treatment-induced antigenic change affect immunization. Bull World Health Organ,2010,88:66-73.
[20] Sainokami S,Abe K,Sato A,et al. Initial load of hepatitis B virus（HBV）,its changing profile,and precore/core promoter mutations correlate with the severity and outcome of acute HBV infection. J Gastroenterol,2007,42:241-249.

39例成人急性乙型肝炎患者血清HBV基因变异检测及其临床意义探讨^*

Hepatitis B viral genotypes and gene mutations in 39 adult patients with acute hepatitis B

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]	邓浩辉, 李晓强, 高洪波, 陈伟烈. HIV/HCV混合感染者与HCV感染者感染HCV基因型分析*[J]. 实用肝脏病杂志, 2019, 22(5): 656-659.
[2]	李芳, 邹桂舟, 叶珺, 郜玉峰. 不同HBV感染转归人群外周血PD-1拷贝数分布研究^*[J]. 实用肝脏病杂志, 2019, 22(1): 37-40.
[3]	张欢欢, 杨欢, 沈思兰, 陈佳婕, 宣彬彬. 慢性乙型肝炎患者HBV基因型分布及其耐药基因突变分析^*[J]. 实用肝脏病杂志, 2019, 22(1): 41-44.
[4]	赵鹏, 王磊. 聚乙二醇化干扰素-α对不同基因型慢性丙型肝炎患者治疗效果比较^*[J]. 实用肝脏病杂志, 2019, 22(1): 57-60.
[5]	谈国蕾, 孙梅, 王建芳, 吴旭平. 汉族人群乙型肝炎病毒感染者外周血IL-28B基因多态性研究^*[J]. 实用肝脏病杂志, 2018, 21(4): 561-564.
[6]	伍宵, 魏少峰, 徐楠, 苏倩, 李旭, 张振华. 中国慢性HBV感染者基因型分布及其临床意义Meta分析^*[J]. 实用肝脏病杂志, 2017, 20(3): 271-275.
[7]	邓家征, 申洋, 凌晶, 邓宏, 乐永红, 庄小芳. 转化生长因子α-435G/A基因多态性与非酒精性脂肪性肝病相互关系研究[J]. 实用肝脏病杂志, 2017, 20(1): 65-68.
[8]	刘菲菲, 张海月, 张倩, 王鲁文, 龚作炯. 慢性丙型肝炎合并2型糖尿病患者临床特征及胰岛素抵抗对抗病毒疗效影响的Meta分析[J]. 实用肝脏病杂志, 2016, 19(4): 436-440.
[9]	郝建宏, 胡忆玲, 林爱清. 慢性乙型肝炎患者HBV基因耐药突变分析[J]. 实用肝脏病杂志, 2016, 19(4): 473-475.
[10]	张撷华, 林爱清, 胡忆玲, 韦丽琴. 102例慢性HBV感染者病毒基因变异情况分析^*[J]. 实用肝脏病杂志, 2016, 19(4): 480-481.
[11]	单奔，孔歌，李彦，王霞，傅涓涓，李丽，潘修成. HBeAg阳性慢性乙型肝炎患者血清Mig、RANTES和IL-9水平与HBV前C/BCP区变异的关系及其对聚乙二醇α-干扰素治疗应答的影响*[J]. 实用肝脏病杂志, 2016, 19(3): 283-287.
[12]	黄鹏宇(综述), 徐东平(审校). 慢加急性乙型肝炎肝衰竭患者乙型肝炎病毒前C/CP区变异研究进展^*[J]. 实用肝脏病杂志, 2016, 19(2): 241-244.
[13]	谢巧灵, 丛庆伟, 吴凌虹, 朱英. 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^*[J]. 实用肝脏病杂志, 2016, 19(1): 60-63.
[14]	哈明昊，佘会元，吴建秋，孙莉萍，沈文娟，黄钟鸣，陈晓兰，单文艳，何慧芳. 乙型肝炎病毒包膜区和核心区CTL抗原表位变异对感染慢性化及疾病转归的影响^*[J]. 实用肝脏病杂志, 2015, 18(6): 581-584.
[15]	关翠英，阿娜尔古丽?穆哈买尔，王亚楠，葛力菲，郭宇. 不同抗病毒治疗方案治疗慢性丙型肝炎患者疗效分析[J]. 实用肝脏病杂志, 2015, 18(5): 496-499.