HBV感染者HBsAg和抗-HBs双阳性发生机制

任美欣; 孟庆华

doi:10.3969/j.issn.1001-5256.2014.04.023

HBV感染者HBsAg和抗-HBs双阳性发生机制

DOI: 10.3969/j.issn.1001-5256.2014.04.023

首都医科大学附属北京佑安医院重症肝病科

详细信息

中图分类号: R512.62
计量
- 文章访问数: 3770
- HTML全文浏览量: 47
- PDF下载量: 782
- 被引次数: 0
出版历程
- 出版日期: 2014-04-20

Research progress in mechanism of coexistence of HBsAg and HBsAb in patients with HBV infection

Department of Severe Liver Disease, Beijing Youan Hospital, Capital Medical University

摘要

摘要:
HBV感染后可产生一种保护性抗体抗-HBs,是病毒清除的典型特征。乙型肝炎表面抗原（HBsAg）和抗-HBs序贯表达,理论上在同一患者不可能同时检出。但是近年来,关于HBsAg和抗-HBs同时阳性的报道屡见不鲜。在临床中,HBsAg和抗-HBs同时阳性的现象多见于慢性乙型肝炎患者,及注射乙型肝炎疫苗或使用大剂量单克隆抗-HBs的患者。对于这种特殊现象的发生机制尚不清楚。总结了国内外相关研究结果,分析表明HBsAg和抗-HBs双阳性可能与HBV S基因变异和抗-HBs结合力下降等有关。
- 肝炎,乙型,慢性 /
- 肝炎表面抗原,乙型 /
- 综述
Abstract:
Hepatitis B surface antibody (HBsAb) is formed in response to hepatitic B virus (HBV) infection, which is a typical characteristic of virus clearance.It is theoretically impossible to detect sequential expression of hepatitis B surface antigen (HBsAg) and HBsAb in the same patient.In recent years, however, cases of coexistence of HBsAg and HBsAb have been frequently reported.Clinically, coexistence of HBsAg and HBsAb is commonly seen in patients with chronic hepatitis B and those injected with hepatitis B vaccine or given high-dose monoclonal anti- HBs.The mechanism of this special phenomenon remains unclear.The relevant research findings in China and the rest of the world are summarized.Analysis shows that coexistence of HBsAg and HBsAb may be related to HBV S gene mutation, decreased binding force of HBsAb, etc.
- hepatitis B, chronic /
- hepatitis B surface antigens /
- review

HTML全文

参考文献(42)

[1] ZHANG JM, XU Y, WANG XY, et al.Coexistence of hepatitis B surface antigen (HBsAg) and heterologous sub-type-specific antibodies to HBsAg among patients with chronic hepatitis B virus infection[J].Clin Infect Dis, 2007, 44 (9) :1161-1169.

[2]KOHNO HT, INOUE F, TSUDA H, et al.Mutations in the envelope gene of hepatitis B virus variants co-occurring with antibody to surface antigen in sera from patients with chronic hepatitis B[J].J Gen Virol, 1996, 77 (Pt 8) :1825-1818.

[3]MIMMS L.Hepatitis B virus escape mutants:pushing the envelope of chronic hepatitis B virus infection[J].Hepatology, 1995, 21 (3) :884-887.

[4]YU YC, MA SW, WANG ZH.HBsAg and HBsAb coexistence in Chinese patients with chronic HBV infection:clinical and virological characteristics[J].J Gastroenterol Hepatol, 2006, 21:a143.

[5] WANG JJ, JI HH, WANG WY.Analysis of 39 cases of both positive mode of HBsAg and HBsAb[J].Med Innov Chin, 2011, 32 (8) :105-107. (in Chinese) 王婧婧, 吉晖晖, 王文燕.39例乙型肝炎表面抗原与表面抗体同时阳性的结果分析[J].中国医学创新, 2011, 32 (8) :105-107.

[6] YANG HW, FANG XL.Coexistence of HBsAg and HBsAb:an analysis of 48 cases[J].World Health Dig, 2011, 8 (12) :424-425.杨华文, 方晓琳.48例乙型肝炎HBsAg与HBsAb同时阳性结果分析[J].中外健康文摘, 2011, 8 (12) :424-425.

[7]LYU JY, ZHANG L, DING YQ.Analysis of coexistence of HBsAg and HBsAb in patients with hepatitis B[J].Lab Med Clin, 2010, 7 (2) :155-156. (in Chinese) 吕建渊, 张莉, 丁一琴.乙型肝炎患者表面抗原与表面抗体同时阳性结果分析[J].检验医学与临床, 2010, 7 (2) :155-156.

[8]WANG YM, NG WC, LO SK.Detection of pre-S/S gene mutants in chronic hepatitis B carries with concurrent hepatitis B surface antibody and hepatitis B surface antigen[J].J Gastroenterol, 1999, 34 (5) :600-606.

[9]COLSON P, BORENTAIN P, MOTTE A, et al.Clinical and virolological significance of the co-existence of HBsAg and anti-HBs antibodies in hepatitis B chronic carriers[J].Virology, 2007, 367 (1) :30-40.

[10]TIAN YJ, XU Y, ZHANG ZH, et al.The amino acid residues at positions 120 to 123 are crucial for the antigenicity of hepatitis B surface antigen[J].J Clin Microbiol, 2007, 45 (9) :2971-2978.

[11] CARMAN WF, ZANE'ITI AR, KARAYIANNIS P, et al.Vacineinduced escape mutant of hepatitis B virus[J].Lancet, 1990, 336 (8711) :325-329.

[12]LADA O, BENHAMOU Y, POYNARD T, et al.Coexistence of hepatitis B surface antigen (1tBsAg) and anti-HBs antibodies in chronic hepatitis B virus carries:influence of“a”determinant variants[J].J Virol, 2006, 80 (6) :2968-2975.

[13] ZHANG ZH, PENG J, XIAO JB, et al.S gene mutations in HBsAg/HBsAb double positive chronic hepatitis B patients[J].Chin J Hepatol, 2009, 17 (4) :266-270. (in Chinese) 张振华, 彭静, 夏剑波, 等.表面抗原和抗体双阳性慢性乙型肝炎病毒感染者病毒S基因的变异分析[J].中华肝脏病杂志, 2009, 17 (4) :266-270.

[14]WANG ZB, ZHOU HY.Ananysis on the rare several serum markers of hepatitis B[J].Lab Med Clin, 2009, 12 (6) :2093-2094. (in Chinese) 王智斌, 周红艳.乙型肝炎血清标志物少见模式分析[J].检验医学与临床, 2009, 12 (6) :2093-2094.

[15]LADA O, BENHAMOU Y, POYNARD T, et al.Coexistence of hepatitis B surface antigen (HBsAg) and anti-HBs antibodies in chronic hepatitis B virus carriers:influence of“a”determinant variants[J].Virol, 2006, 80 (6) :2968-2975.

[16]WANG L, LIU H, NING X, et al.Sequence analysis of the S gene region in HBV DNA from patients positive for both HBsAg and HBsAb tests[J].Hepatol Res, 2010, 40 (12) :1212-1218.

[17]ZHANG ZH, PENG J, YANG DL, et al.S gene mutations in HBsAg/HBsAb double positive chronic hepatitis B patients[J].Chin J Hepatol, 2009, 17 (4) :266-270. (in Chinese) 张振华, 彭静, 杨东亮, 等.表面抗原和抗体双阳性慢性乙型肝炎病毒感染者病毒S基因的变异分析[J].中华肝脏病杂志, 2009, 17 (4) :266-270.

[18]HUANG XY, QIN YH, ZHANG P, et al.PreS deletion mutations of hepatitis B virus in chronically infected patients with simultaneous seropositivity for hepatitis-B surface antigen and anti-HBs antibodies[J].J Med Virol, 2010, 82 (1) :23-31.

[19]YAN XP, ZHANG K, WANG F.Analysis of coexistence of HBsAg and HBsAb in patients with hepatitis B[J].J Clin Hepatol, 2008, 24 (2) :91-93. (in Chinese) 闫秀萍, 张凯, 王峰.HBsAg与抗-HBs同时阳性慢性乙肝患者HBV基因全序列分析[J].临床肝胆病杂志, 2008, 24 (2) :91-93.

[20]MATHET VL, FELD M, ESPLNOLA L, et al.Hepatitis B virus S gene mutants in a patient with chronic active hepatitis with circulating Anti-HBs antibodies[J].J Med Virol, 2003, 69 (1) :18-26.

[21]CHEN Y, QIAN F, YUAN Q, et al.Mutations in hepatitis B virus DNA from patients with coexisting HBsAg and anti-HBs[J].J Clin Virol, 2011, 52 (3) :198-203.

[22] ZHOU XM, LI AD, YU WH, et al.Effect of“a”determinant variants on expression of HBsAg and HBsAb in patients with chronic hepatitis B[J].J Chin Physician, 2008, 10 (4) :453-455. (in Chinese) 周小梅, 李爱娣, 余文辉, 等.“a”决定簇变异对慢性乙型肝炎患者HBsAg与HBsAb表达的影响[J].中国医师杂志, 2008, 10 (4) :453-455.

[23]HSU HY, CHANG MH, NI YH, et al.Survey of hepatitis B surface variant infection in children 15 years after a nationgwide vaccination programme in Taiwan[J].Gut, 2004, 53 (10) :1499-1503.

[24] MATHET VL, FELD M, ESPINOLA L, et al.Hepatitis B virus S gene mutants in a patient with chronic active hepatitis with circulating anti-HBs antibodies[J].Med Virol, 2003, 69 (1) :18-26.

[25]POLLICINO T, AMADDEO G, RESTUCCIA A, et al.Impact of hepatitis B virus (HBV) preS/S genomic variability on HBV surface antigen and HBV DNA serum levels[J].Hepatology, 2012, 56 (2) :434-443.

[26]LIU SZ, SUN DX.Research advances in hepatitis B virus PreS1[J].Int J Virol, 2012, 19 (5) :232-236. (in Chinese) 刘石柱, 孙殿兴.乙型肝炎病毒PreS1的研究进展[J].国际病毒学杂志, 2012, 19 (5) :232-236.

[27]JANG JS, KIM HS, KIM HJ, et al.Association of concurrent hepatitis B surface antigen and antibody to hepatitis B surface antigen with hepatocellular carcinoma in chronic hepatitis B virus infection[J].J Med Virol, 2009, 81 (9) :1531-1538.

[28]ZHOU Y, XIONG Y, LIU JH.The analysis of“a”determinant mutations of hepatitis B virus infecting children in Jiangxi province[J].Chin J Immunol, 2012, 28 (2) :168-171. (in Chinese) 周艳, 熊英, 刘全辉.江西地区儿童感染的乙型肝炎病毒“a”抗原变异分析[J].中国免疫学杂志, 2012, 28 (2) :168-171.

[29]ZHU P, LIN WT.Practical clinical immunology[M].Beijing:High Education Press, 2008:358-359. (in Chinese) 朱平, 林文棠.实用临床免疫学[M].北京:高等教育出版社, 2008:358-359.

[30] LEE KM, KIM YS, KO YY, et al.Emergence of HBsAb vaccineinduced escape of hepatitis B virus with multiple surface gene mutations in a Korean child[J].J Korean Med Sci, 2001, 16 (3) :359-362.

[31]HEIJTINK RA, van BERGEN P, van ROOSMALEN MH, et al.Anti-HBs after hepatitis B immunization with plasma-derived and recombinant DNA-derived vaccines:binding to mutant HBsAg[J].Vaccine, 2001, 19 (27) :3671-3680.

[32]WANG JJ, YAN TQ, LI QS, et al.Molecular epidemiological characteristics of“a”determinant mutation in HBsAg carriers after immunization with hepatitis B vaccine only[J].Pract Prevent Med, 2002, 9 (2) :106-109. (in Chinese) 王继杰, 颜天强, 李乔生, 等.单纯乙型肝炎疫苗免疫后表面抗原携带者“a”决定簇基因突变的分子流行病学特征[J].实用预防医学, 2002, 9 (2) :106-109.

[33]LONG HY, WANG SW, YAN YW.Detection of hepatitis B surface antigen mutants[J].Inter J Epidemiol Infect Dis, 2006, 33 (4) :271-274. (in Chinese) 龙厚玉, 王思望, 严有望.乙型肝炎病毒表面抗原变异的检测[J].国际流行病学传染病学杂志, 2006, 33 (4) :271-274.

[34]LIU CJ, KAO JH, SHAU WY, et al.Naturally occurring hepatitis B surface gene variants in chronic hepatitis B virus infection:correlation with viral serotypes and clinical stages of liver disease[J].J Med Virol, 2002, 68 (1) :50-59.

[35]SLOAN RD, IJAZ S, MOORE PL, et al.Antiviral resistance mutations potentiate hepatitis B virus immune evasion through disruption of its surface antigen a determinant[J].Antivir Ther, 2008, 13 (3) :439-447.

[36]LU HY, ZENG Z, XU XY, et al.Mutations in surface and polymerase gene of chronic hepatitis B patients with coexisting HBsAg and anti-HBs[J].World J Gastroenterol, 2006, 12 (26) :4219-4223.

[37]SHIELS MT, TASWELL HF, CZAJA AJ, et al.Frequency and significance of concurrent hepatitis B surface antigen and antibody in acute and chronic hepatitis B[J].Gastroenterology, 1987, 93 (4) :675-680.

[38]TABOR E, GERETY RJ, SMALLWOOD LA, et al.Coincident hepatitis B surface antigen and antibody of different subtypes in human serum[J].J Immunol, 1977, 18 (1) :369-370.

[39]YU LC, MA SW, WANG XG, et al.The correlations between HBV genotypes and HBsAg mutaion and coexistence of HBsAg/anti-HBs in patients with chronic hepatitis B[J].Chin Hepatol, 2010, 15 (4) :259-264. (in Chinese) 于乐成, 马世武, 王雪刚, 等.HBV基因型和S基因序列特点与慢性乙型肝炎患者HBsAg/抗-HBs共存关系[J].肝脏, 2010, 15 (4) :259-264.

[40]WANG L, LIU H, NING XX, et al.Relationship between genotypes and mutations in S gene sequence of chronic hepatitis B patients with positive results for both HBsAg and HBsAb tests[J].J Shanghai Jiaotong Univ:Med Sci, 2010, 30 (10) :1226-1230. (in Chinese) 王蕾, 刘华, 宁小晓, 等.HBsAg和HBsAb双阳性慢性乙肝患者血清中HBV基因型与S区突变的关系[J].上海交通大学学报:医学版, 2010, 30 (10) :1226-1230.

[41]YUKIMASA N, MATSUDA R, YASUHARA T, et al.The relation between virus genotypes and coexisting surface antigen and antibody in patients with hepatitis B and the development of pre S region deletions[J].Rinsho Byori, 2005, 53 (8) :698-702.

[42]ZHAO XY, CHEN JM, WANG WJ, et al.Comparison study and analysis of detecting HBsAb using ECLIA and ELISA[J].Beijing Med J, 2011, 33 (6) :461-463. (in Chinese) 赵秀英, 陈俊梅, 王文静, 等.电化学发光法和ELISA法检测HBV表面抗体结果的比较与分析[J].北京医学, 2011, 33 (6) :461-463.

施引文献

资源附件(0)

访问统计