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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 35 Issue 4
Apr.  2019
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Article Contents

Association between HBeAg-negative chronic hepatitis B and pre C/BCP mutation

DOI: 10.3969/j.issn.1001-5256.2019.04.038
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  • Published Date: 2019-04-20
  • Studies on the HBV gene have shown that HBeAg-negative chronic hepatitis B ( CHB) is associated with gene mutations in the pre-C ( preC) and basic core promoter ( BCP) region of HBV DNA, and it is pointed out that the mutation in the preC/BCP region can affect the expression of serum HBeAg and is closely associated with the low replication of HBV DNA in the body, the progression of diseases, and the response to antiviral therapy, which makes the treatment of CHB more complicated. This article reviews the current status of the treatment of HBeAg-negative CHB, structure and mutation of HBV preC/BCP region, and the influence of mutation on the progression of HBeAg-negative CHB and the effect of antiviral therapy for hepatitis B.

     

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  • [1]OTT JJ, STEVWNS GA, GROEGER J, et al. Global epidemiology of hepatitis B virus infection:New estimates of age-specific HBsAg seroprevalence and endemicity[J]. Vaccine, 2012, 30 (12) :2212-2219.
    [2]LU FM, ZHUANG H. Management of hepatitis B in China[J].Chin Med J (Engl) , 2009, 122 (1) :3-4.
    [3]WANG FS, FAN JG, ZHANG Z, et al. The global burden of liver disease:The major impact of China[J]. Hepatology, 2014, 60 (6) :2099-2108.
    [4]Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association. The guideline of prevention andtreatment for chronic hepatitis B:A 2015 update[J]. J Clin Hepatol, 2015, 31 (12) :1941-1960. (in Chinese) 中华医学会肝病学分会, 中华医学会感染病学分会.慢性乙型肝炎防治指南 (2015年更新版) [J].临床肝胆病杂志, 2015, 31 (12) :1941-1960.
    [5]YU HB, ZHAI Y, SUN YN, et al. Clinical characteristics of HBe Ag positive and HBe Ag negative chronic hepatitis B[J].Chin Clin Dr, 2017, 45 (2) :35-38. (in Chinese) 于海滨, 翟云, 孙亚男, 等. HBe Ag阴性及HBe Ag阳性慢性乙型肝炎患者的临床特征比较[J].中国临床医生杂志, 2017, 45 (2) :35-38.
    [6]LI W, CHEN G, YU X, et al. Accumulation of the mutations in basal core promoter of hepatitis B virus subgenotype C1 increase the risk of hepatocellular carcinoma in Southern China[J]. Int J Clin Exp Pathol, 2013, 6 (6) :1076-1085.
    [7]LYU H, LEE D, CHUNG YH, et al. Synergistic effects of Al896, T1653 and T1762/A l764 mutations in genotype c2 hepatitis B virus on development of hepatocellular carcinoma[J]. J Viral Hepat, 2013, 20 (3) :219-224.
    [8]GAO SX. The research progress of hepatitis B virus e antigen[J]. Med Recapitulate, 2011, 17 (14) :2151-2153. (in Chinese) 高尚秀.乙型肝炎病毒e抗原的研究进展[J].医学综述, 2011, 17 (14) :2151-2153.
    [9]OKAMOTO H, TSUDA F, AKAHANE Y. Hepatitis B virus with mutations in the e antigen-negative phenotype in carriers with e antibody to e antigen[J]. Virol, 1994, 68 (12) :8102-8110.
    [10]ALESTIG E, HANNOUN C, HORAL P, et al. Phylogenetic origin of hepatitis B virus strains with precore-1858 variant[J].J Clin Microbiol, 2001, 39 (9) :3200-3203.
    [11]LUO KX. Hepatitis B basic biology and clinical science[M].Beijing:People’s Medical Publishing House, 2006:56-57. (in Chinese) 骆抗先.乙型肝炎基础和临床[M].北京:人民卫生出版社, 2006:56-57.
    [12]LI JE, CHEN XY. Recent progress in research of hepatitis B viruses with precore and basic core promoter mutations[J]. J Clin Hepatol, 2013, 29 (2) :88-92. (in Chinese) 李金娥, 陈新月.乙型肝炎病毒前C/BCP区变异的研究现状[J].临床肝胆病杂志, 2013, 29 (2) :88-92.
    [13]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.
    [14]LIN CL, KAO JH. Hepatitis B virus genotypes and variants[J].Cold Spring Harb Perspect Med, 2015, 5 (5) :a021436.
    [15]ALEXOPOLOU A, KARAYIANNIS P. HBe Ag negative variants and their role in the natural history of chronic hepatitis B virus infection[J]. World J Gastroenterol, 2014, 20 (24) :7644-7652.
    [16]HUSSAIN Z, JUNG HS, RYU DK, et al. Genetic dissection of naturally occurring basal core promoter mutations of hepatitis B virus reveals a silent phenotype in the overlapping X gene[J].J Gen Virol, 2009, 90 (9) :2272-2281.
    [17]TONG MJ, PAN CQ, HARM HW, et al. The management of chronic hepatitis B in Asian Americans[J]. Dig Dis Sci, 2011, 56 (11) :3143-3162.
    [18]ZONG L, QIN Y, JIA H, et al. Differential regulation of hepatitis B virus core protein expression and genome replication by a small upstream open reading frame and naturally occurring mutations in the precore region[J]. Virology, 2017, 505 (5) :155-161.
    [19]XU YJ, SONG WQ. Association of mutations in basal core promoter and precore region of hepatitis B virus with progress of liver disease[J]. Chin J Clin Infect Dis, 2012, 5 (4) :253-256. (in Chinese) 徐尧江, 宋伟泉. HBV基本核心启动子区和前C区变异与肝病进展的关系[J].中华临床感染病杂志, 2012, 5 (4) :253-256.
    [20]ZHOU WH, DING SX, WENG PJ. Effects of HBV pre-core and basal core promoter mutations on serum HBV DNA level in chronic hepatitis B using Gene-chip technique[J]. J Chin Physic, 2006, 8 (3) :350-352. (in Chinese) 周文红, 丁世雄, 翁彭剑.乙型肝炎病毒前C区/BCP区突变对血清HBV DNA含量的影响[J].中国医师杂志, 2006, 8 (3) :350-352.
    [21]SUN M, CHEN QZ, ZHAO HJ, et al. Clinical significance of PC/BCP region variation and the serum parameters in HBV chronic infection patients[J]. Chin Trop Med, 2017, 17 (9) :912-914, 924. (in Chinese) 孙敏, 陈巧真, 赵华菊, 等. HBV慢性感染者PC/BCP区变异特点及血清检测指标临床意义[J].中国热带医学, 2017, 17 (9) :912-914, 924.
    [22]WANG XL, REN JP, WANG XQ, et al. Mutations in pre-core and basic core promoter regions of hepatitis B virus in chronic hepatitis B patients[J]. World J Gastroenterol, 2016, 22 (11) :3268-3274.
    [23]DENG YJ, QIAN J. Pre-C/basic core promoter gene mutation in chronic HBV infection and its clinical application[J].Chin J Integr Tradit West Med Liver Dis, 2015, 25 (4) :239-241. (in Chinese) 邓拥军, 钱军.慢性HBV感染者HBV前C区/基本核心启动子区基因突变与临床应用[J].中西医结合肝病杂志, 2015, 25 (4) :239-241.
    [24]CHACHA SGF, GOMES-GOUVEA MS, MALTA FM, et al.Basal core promoter and precore mutations among hepatitis B virus circulating in Brazil and its association with severe forms of hepatic diseases[J]. Mem Inst Oswaldo Cruz, 2017, 112 (9) :626-631.
    [25]ZHOU H, GEWAILY D, AHN SH, et al. Sequence analysis and functional characterization of full-length hepatitis B virus genomes from Korean cirrhotic patients with or without liver cancer[J]. Virus Res, 2017, 235:86-95.
    [26]PARK YM, JANG JW, YOO SH, et al. Combinations of eight key mutations in the X/preC region and genomic activity of hepatitis B virus are associated with hepatocellular carcinoma[J]. J Viral Hepat, 2014, 21 (3) :171-177.
    [27]WEI F, ZHENG Q, LI M, et al. The association between hepatitis B mutants and hepatocellular carcinoma:A meta-analysis[J]. Medicine (Baltimore) , 2017, 96 (19) :e6835.
    [28]MALIK A, SINGHAL DK, ALBANYAN A. Hepatitis B virus gene mutations in liver diseases:A report from New Delhi[J]. PLo S One, 2012, 7 (6) :e39028.
    [29]WANG M, HU YF, SHI WT, et al. Associations between hepatitis B virus X gene mutations and hepatocellular carcinoma[J]. Chin J Hepatol, 2015, 23 (8) :599-603. (in Chinese) 王淼, 胡艳芳, 史为涛, 等.原发性肝细胞癌患者乙型肝炎病毒X基因突变检测及其临床意义[J].中华肝脏病杂志, 2015, 23 (8) :599-603.
    [30]CHEN F, LI CS. Relationship between HBV base core promoter and precore mutation with hepatocellular carcinoma in HBe Ag negative patients[J]. Jiangsu Med J, 2017, 43 (6) :418-421. (in Chinese) 陈飞, 李传生. HBV基本核心启动子区和前C区变异与HBe Ag阴性患者肝癌发生的关系[J].江苏医药, 2017, 43 (6) :418-421.
    [31]ELIZALDE MM, SEVIC I, GONZLEZ LPEZ LEDESMA MM, et al. Human hepatocytes apoptosis induced by replication of hepatitis B virus subgenotypes F1b and F4:Role of basal core promoter and preCore mutations[J]. Virology, 2018, 513 (1) :160-167.
    [32] HAN YP, LI J, JIANG LF, et al. Hepatitis B e antigen from chronic hepatitis B patients induces Th1/Th2 cytokine imbalance in vitro[J]. Chin J Hepatol, 2013, 21 (8) :584-589. (in Chinese) 韩亚萍, 李军, 蒋龙凤, 等. HBe Ag导致慢性乙型肝炎患者外周血Th1/Th2型细胞因子失衡[J].中华肝脏病杂志, 2013, 21 (8) :584-589.
    [33]JIANG XH, LI XF. The relationship between HBV precore and basal core promoter mutations and serum cytokines in patients with chronic hepatitis B[J]. Chin J Infect Control, 2010, 9 (5) :320-323. (in Chinese) 蒋孝华, 李小芬.慢性乙型肝炎患者HBV前C区及BCP区变异与血清细胞因子的关系[J].中国感染控制杂志, 2010, 9 (5) :320-323.
    [34] GUO W. A study on Hepatitis B virus BCP/Pre-C gene mutations and Th1/Th2 immunological condition in Patients with chronic severe hepatitis B[D]. Wuhan:Huazhong University of Science and Technology, 2006:1-74. (in Chinese) 郭威.慢性重型乙型肝炎患者HBV BCP/前C区基因变异及Th1/Th2免疫状态的研究[D].武汉:华中科技大学, 2006:1-74.
    [35]GAO HB, WANG XM, LIU BR, et al. Expression of Treg and Th17in HBV-related acute-on-chronic liver failure patients and their correlations with the mutations in HBV pre-C/BCP region[J].Chin Hepatol, 2018, 23 (1) :18-21, 86. (in Chinese) 高海兵, 王香梅, 刘宝荣, 等. HBV相关慢加急性肝衰竭患者Treg细胞、Th17细胞表达特点及其与HBV前C区/BCP区变异的相关性[J].肝脏, 2018, 23 (1) :18-21, 86.
    [36]YANG S, XING HC, CHENG J. Progress in hepatitis B virus resistance to nucleos (t) ide analogues[J/CD]. Chin J Exp Clin Infect Dis:Electronic Edition, 2018, 12 (1) :1-6. (in Chinese) 杨松, 邢卉春, 成军.乙型肝炎病毒核苷 (酸) 类似物耐药研究进展[J/CD].中华实验和临床感染病杂志:电子版, 2018, 12 (1) :1-6.
    [37]SONG BC, CUI XJ, SHIN JW, et al. Response to adefovir depends on mutation patterns in precore region, basal core promoter and reverse transcriptase, and on-treatment responses in Lamivudine-resistant chronic hepatitis B patients[J].Intervirology, 2010, 53 (4) :203-210.
    [38]BELYHUN Y, LIEBERT UG, MAIE M. Analysis of HBV basal core promoter/precore gene variability in patients with HBV drug resistance and HIV co-infection in Northwest Ethiopia[J]. PLo S One, 2018, 13 (2) :e0191970.
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