|本期目录/Table of Contents|

[1]储 芳,钟彦伟,杨红艳,等.儿童慢性乙型肝炎患者HBV 前C/ 基本核心启动子区基因变异特点研究[J].传染病信息,2018,06:541-543576.
 CHU Fang,ZHONG Yan-wei,YANG Hong-yan,et al.Gene mutations of hepatitis B virus precore/basal core promoter region in children with chronic hepatitis B virus infection[J].Infectious Disease Information,2018,06:541-543576.
点击复制

儿童慢性乙型肝炎患者HBV 前C/ 基本核心启动子区基因变异特点研究(PDF)

《传染病信息》[ISSN:1007-8134/CN:11-3886/R]

期数:
2018年06期
页码:
541-543576
栏目:
论 著
出版日期:
2018-12-30

文章信息/Info

Title:
Gene mutations of hepatitis B virus precore/basal core promoter region in children with chronic hepatitis B virus infection
作者:
储 芳钟彦伟杨红艳王 丹温梦凡刘 超孙群兰李 晶张 明官卉卉王文波张 敏
545005 柳州,广西壮族自治区龙潭医院感染性疾病科 (蒙志好、左勇、邬剑威);201508,上海市公共卫生临床中心感 染与免疫科(沈银忠)
Author(s):
CHU Fang ZHONG Yan-wei YANG Hong-yan WANG Dan WEN Meng-fan LIU Chao SUN Qun-lan LI Jing ZHANG Ming GUAN Hui-hui WANG Wen-bo* ZHANG Min*
Pediatric Liver Disease Therapy Research Laboratory, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China CHU Fang and ZHONG Yan-wei are the first authors who contributed equally to the article
关键词:
儿童慢性乙型肝炎前C 区基本核心启动子区变异
Keywords:
children chronic hepatitis B precore basal core promoter mutation
分类号:
R373.21  
DOI:
10.3969/j.issn.1007-8134.2018.06.011
文献标识码:
A
摘要:
目的 探讨慢性乙型肝炎(慢乙肝)患儿HBV 前C(procore, PC)/ 基本核心启动子(basic core promoter, BCP)区的变异特点。方法 收集符合慢乙肝和肝硬化诊断标准的患儿血清166 例。采用DNAout 方法提取血清HBV DNA;巢式PCR 方法扩增HBV PC/BCP 区序列,PCR 产物纯化后直接测序。分析HBV PC/BCP 区相关位点变异情况。 结果 166 例患儿中,HBV B 基因型的患儿占比20.83%,HBV C 基因型的患儿占比79.17%。在感染HBV B 基因型的患儿 中,乙型肝炎(乙肝)肝硬化患儿与慢乙肝患儿的HBV DNA 水平无明显差异,但前者G1899A 位点突变率高于后者。在 感染HBV C 基因型的患儿中,与慢乙肝患儿相比,乙肝肝硬化患儿发生 A1762T/G1764A、G1896A 突变的比率明显升高且 ALT 水平较高。结论 HBV C 基因型,ALT 水平升高,发生A1762T/G1764A,G1896A 位点变异的患儿,更容易发展为乙 肝相关肝硬化。  
Abstract:
Objective To investigate the characteristics of HBV precore (PC) and basal core promoter (BCP) region gene mutations in children with chronic hepatitis B (CHB). Methods A total of 166 children with CHB and liver cirrhosis (LC) were enrolled in this study and their serum samples were collected. Serum HBV DNA was extracted with DNAout method; the sequence in HBV PC/BCP region was amplified with nested PCR method, and PCR products were determined by direct sequencing after purification. Mutations of the HBV PC/BCP region were analyzed. Results Among the 166 children, 20.83% of cases had HBV genotype B and 79.17% of cases had HBV genotype C. In children of HBV genotype B infection, there was no significant difference in HBV DNA levels between LC children and CHB children, but the G1899A mutations were prevalent in LC children. In children of HBV genotype C infection, the A1762T/ G1764A, G1896A mutations were significantly prevalent and alanine aminotransferase level was also incr eased in LC children compared with CHB children. Conclusions Children patients with HBV genotype C virus, high alanine aminotransferase, A1762T/ G1764A, G1896A mutant virus are more susceptible to develop HBV-related LC.  

参考文献/References


[1] Liang X, Bi S, Yang W, et al. Epidemiological serosurvey of hepatitis B in China--declining HBV prevalence due to hepatitis B vaccination[J]. Vaccine, 2009, 27(47):6550-6557.
[2] Liang X, Bi S, Yang W, et al. Evaluation of the impact of hepatitis B vaccination among children born during 1992-2005 in China[J]. J Infect Dis, 2009, 200(1):39-47.
[3] Sayed SK, Kobeisy MA. The relationship between core promoter mutation of hepatitis B virus, viral load and hepatitis B e antigen status in chronic hepatitis B patients[J]. Cell Immunol, 2012, 276(1-2):35-41.
[4] 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[J]. Hepatology, 2006, 44(2):326-334.
[5] Xu Z, Ren X, Liu Y, et al. Association of hepatitis B virus mutations in basal core promoter and precore regions with severity of liver disease: an investigation of 793 Chinese patients with mild and severe chronic hepatitis B and acute-on-chronic liver failure [J]. J Gastroenterol, 2011, 46(3):391-400.
[6] Liu Y, Zhong Y, Zhou 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]. J Clin Virol, 2010, 47(3):243-247.
[7] Tacke F, Gehrke C, Luedde T, et al. Basal core promoter and precore mutations in the hepatitis B virus genome enhance replication efficacy of Lamivudine-resistant mutants[J]. J Virol, 2004, 78(16):8524-8535.
[8] Cui XJ, Cho YK, Song BC. Influence of the basal core promoter and precore mutation on replication of hepatitis B virus and antiviral susceptibility of different genotypes[J]. J Med Virol, 2015, 87(4):601-608.
[9] Ferns RB, Naoumov NV, Gilson RJ, et al. Presence of hepatitis B virus core promoter mutations pre-seroconversion predict persistent viral replication after HBeAg loss[J]. J Clin Virol, 2007, 39(3):199-204.
[10] Tabernero D, Sánchez MJ, Homs M, et al. Main mutations in the hepatitis B virus basic core promoter (A1762T/G1764A) before HBeAg loss are markers that identify patients who will require long-term treatment[J]. Aliment Pharmacol Ther, 2010, 32(1):97-104.
[11] Yuen MF, Sablon E, Yuan HJ, et al. Relationship between the development of precore and core promoter mutations and hepatitis B e antigen seroconversion in patients with chronic hepatitis B virus[J]. J Infect Dis, 2002, 186(9):1335-1338.
[12] Chauhan R, Kazim SN, Bhattacharjee J, et al. Basal core promoter, precure region mutations of HBV and their association with e antigen, genotype, and severity of liver disease in patients with chronic hepatitis B in India[J]. J Med Virol, 2006, 78(8):1047- 1054.
[13] Kamijo N, Matsumoto A, Umemura T, et al. Mutations of precure and basal core promoter before and after hepatitis B e antigen seroconversion[J]. World J Gastroenterol, 2015, 21(2):541-548.
[14] Yang HC, Chen CL, Shen YC, et al. Distinct evolution and predictive value of hepatitis B virus precore and basal core promoter mutations in interferon-induced hepatitis B e antigen seroconversion[J]. Hepatology, 2013, 57(3):934-943.
[15] Lyu H, Lee D, Chung YH, et al. Synergistic effects of A1896, T1653 and T1762/A1764 mutations in genotype C2 hepatitis B virus on development of hepatocellular carcinoma[J]. J Viral Hepatitis, 2013, 20(3):219-224.
[16] Zhang D, Ma S, Zhang X, et al. Prevalent HBV point mutations and mutation combinations at BCP/preC region and their association with liver disease progression[J]. BMC Infect Dis, 2010, 10:271.
[17] Chen CH, Lee CM, Lu SN, et al. Comparison of sequence changes of precore and core promoter regions in HBeAg-positive chronic hepatitis B patients with and without HBeAg clearance in lamivudine therapy[J]. J Hepatol, 2006, 44(1):76-82.
[18] Juniastuti, Utsumi T, Aksono EB, et al. Predominance of precure mutations and clinical significance of basal core promoter mutations in chronic hepatitis B virus infection in Indonesia[J]. Biomed Rep, 2013, 1(4):522-528.
[19] Makondo E, Bell TG, Kramvis A. Genotyping and molecular characterization of hepatitis B virus from human immunodeficiency virus-infected individuals in southern Africa[J]. PLoS One, 2012, 7(9):e46345.
[20] Datta S, Ghosh A, Dasgupta D, et al. Novel point and combomutations in the genome of hepatitis B virus-genotype D: characterization and impact on liver disease progression to hepatocellular carcinoma[J]. PLoS One, 2014, 9(10):e110012.
[21] Jammeh S, Tavner F, Watson R, et al. Effect of basal core promoter and pre-core mutations on hepatitis B virus replication[J]. J Gen Virol, 2008, 89(Pt 4):901-909.
[22] Ren X, Xu Z, Liu Y, et al. Hepatitis B virus genotype and basal core promoter/precore mutations are associated with hepatitis B-related acute-on-chronic liver failure without pre-existing liver cirrhosis[J]. J Viral Hepatitis, 2010, 17(12):887-895.
[23] Asim M, Malik A, Sarma MP, et al. Hepatitis B virus BCP, precore/ core, X gene mutations/genotypes and the risk of hepatocellular carcinoma in India[J]. J Med Virol, 2010, 82(7):1115-1125.

备注/Memo

备注/Memo:
[ 基金项目] 北京市科技计划课题(Z171100001017182)
[ 作者单位] 100039 北京,中国人民解放军总医院第五医学中心 青少年肝病诊疗与研究中心(储芳、钟彦伟、杨红艳、王丹、温梦凡、 刘超、孙群兰、李晶、张明、官卉卉、王文波、张敏) 前两位作者对本文有同等贡献,均为第一作者
[通信作者] 王文波,E-mail: beijing67907@163.com;张敏,E-mail: zhangmin302302@163.com
更新日期/Last Update: 2018-12-30