乙型肝炎病毒宫内传播的多因素分析
摘要
一、研究背景和目的
乙型病毒性肝炎(简称乙肝)是法定乙类传染病,具有传染性强、传播途径复杂、流行面广泛、发病率高。部分乙肝患者可演变为慢性,并可发展为肝硬化和原发性肝癌,成为一个严重的公共卫生问题。全球60亿人口中,约有1/2人口生活在乙肝病毒(HBV)高流行区,约20亿人证明有HBV感染,3～4亿人为HBV临床感染,这些慢性感染人群其中25～40%最终将死于肝硬化和肝癌。世界卫生组织报告,全球每年因乙肝死亡约75万例,为第七大死亡原因。我国属于HBV高和中流行区,且主要感染年龄为围产期和幼儿期。这两个时期的感染来源往往为宫内感染以及出生后母乳喂养及密切生活接触,仅极少部分为来自父系的遗传传递。
过去认为宫内传播率较低,近来国内外学者通过对乙肝患者引产的胎儿胎盘病理分析提示宫内感染率大于过去的估计。急性乙肝
Background and ObjectiveHepatitis B(HB), the legal B contagious disease, has the character of complicated spreading way. Parts of hepatitis B patients will develop chronic carriers, and even to cirrhosis and original liver cancer. It is a serious public health problem. About 1/2 population of 600 million on the earth live in high spreading area of hepatitis B virus (HBV), about 200 million people were proved HBV infected, 30~40 million of among them were clinical infected, 25%~40% of which will be dead for cirrhosis or liver cancer. World Health Organization (WHO) reported that 750 thousand death cases owe to HBV. Our country belongs to the high and middle spreading area, where most of cases happened during the perinatal period and childhood. Transmission patterns include
intrauterine infection, mother milk feeding, living engage closely and little father heredity.In the past, it was believed that there was a low rate of intrauterine infection. But recent standpoint was said that the situation were more serious. For this reason, to control intrauterine infection will prevent the rage of HB effectually. In order to achieve the aim, we investigate the serum of HBV carrier mothers and later of their infants.Materials and Methods1. MaterialsHBV carrier mothers and later their infants. 57 mothers and their 57 infants were followed for 9 — 18 months. Their serum was investigated.2. MethodsHBVM was measured by ECL methods. HBV-DNA was detected byQ-PCR.3. Statistical analysisAll the data were analyzed using SPSS 10.0 Statistical analysis software. Student's x2'test was used to analysis differences between infected group and control group.
Results1. 8 of 57 newborn infants were observed infected, the rate of infection was 14.04%.2. Comparing with peripheral venous blood sample, the sensitivity and positive predictive value of HBV detected in cords was 100.00%, 80.00%respectively.3. 9-—-18 months later, 14 of the infants became HBV chronic carriers.4. The fetal infectious rate in mothers with HBeAg or HBV-DNA positive was 86.67%, 100.00%, respectively which was significantly higher than that in mothers with HBeAg or HBV-DNA negative. PO.01.Conclusions1. HBeAg or HBV-DNA positive in mothers is one of the risk factors of intrauterine infection.2. HBeAg or HBV-DNA negative mothers are also infectious.3. Detection of HBV-DNA in cord blood is a sensitive index for diagnosing fetal infection , however detection of peripheral venous blood is with the significance of making correct diagnosis.
乙型病毒性肝炎(简称乙肝)是法定乙类传染病,具有传染性强、传播途径复杂、流行面广泛、发病率高。部分乙肝患者可演变为慢性,并可发展为肝硬化和原发性肝癌,成为一个严重的公共卫生问题。全球60亿人口中,约有1/2人口生活在乙肝病毒(HBV)高流行区,约20亿人证明有HBV感染,3～4亿人为HBV临床感染,这些慢性感染人群其中25～40%最终将死于肝硬化和肝癌。世界卫生组织报告,全球每年因乙肝死亡约75万例,为第七大死亡原因。我国属于HBV高和中流行区,且主要感染年龄为围产期和幼儿期。这两个时期的感染来源往往为宫内感染以及出生后母乳喂养及密切生活接触,仅极少部分为来自父系的遗传传递。
过去认为宫内传播率较低,近来国内外学者通过对乙肝患者引产的胎儿胎盘病理分析提示宫内感染率大于过去的估计。急性乙肝
Background and ObjectiveHepatitis B(HB), the legal B contagious disease, has the character of complicated spreading way. Parts of hepatitis B patients will develop chronic carriers, and even to cirrhosis and original liver cancer. It is a serious public health problem. About 1/2 population of 600 million on the earth live in high spreading area of hepatitis B virus (HBV), about 200 million people were proved HBV infected, 30~40 million of among them were clinical infected, 25%~40% of which will be dead for cirrhosis or liver cancer. World Health Organization (WHO) reported that 750 thousand death cases owe to HBV. Our country belongs to the high and middle spreading area, where most of cases happened during the perinatal period and childhood. Transmission patterns include
intrauterine infection, mother milk feeding, living engage closely and little father heredity.In the past, it was believed that there was a low rate of intrauterine infection. But recent standpoint was said that the situation were more serious. For this reason, to control intrauterine infection will prevent the rage of HB effectually. In order to achieve the aim, we investigate the serum of HBV carrier mothers and later of their infants.Materials and Methods1. MaterialsHBV carrier mothers and later their infants. 57 mothers and their 57 infants were followed for 9 — 18 months. Their serum was investigated.2. MethodsHBVM was measured by ECL methods. HBV-DNA was detected byQ-PCR.3. Statistical analysisAll the data were analyzed using SPSS 10.0 Statistical analysis software. Student's x2'test was used to analysis differences between infected group and control group.
Results1. 8 of 57 newborn infants were observed infected, the rate of infection was 14.04%.2. Comparing with peripheral venous blood sample, the sensitivity and positive predictive value of HBV detected in cords was 100.00%, 80.00%respectively.3. 9-—-18 months later, 14 of the infants became HBV chronic carriers.4. The fetal infectious rate in mothers with HBeAg or HBV-DNA positive was 86.67%, 100.00%, respectively which was significantly higher than that in mothers with HBeAg or HBV-DNA negative. PO.01.Conclusions1. HBeAg or HBV-DNA positive in mothers is one of the risk factors of intrauterine infection.2. HBeAg or HBV-DNA negative mothers are also infectious.3. Detection of HBV-DNA in cord blood is a sensitive index for diagnosing fetal infection , however detection of peripheral venous blood is with the significance of making correct diagnosis.
引文
[1] WHO and CDC fact sheets.www.who.int and www.cdc.gov.
[2] 赵连三等.乙型肝炎病毒感染经精子传播的可能性研究[J].中华传染病杂志,1998,16(3):154-157.
[3] Tang S L,Hsu H Y, Lin H H, et al.Hepatits B surface antigenemia at birth, a long-term follow-up [J]. J Pediatr,1998,133(3),374-377.
[4] Tiollais P, etal.The hepatitis B virus[J].Nature,1985,317:489
[5] Bonino F, Importance of hepatits B virus DNA in serum and liver [J], J Hepotol, 1986,3:136.
[6] Torresi J, Earmeat-Silveim L, Deliyannis G, et al. Reduced antigenicity of the hepatitis B virus HBsAg protein arising as a consequence of sequence changes in the overlapping polymerase gene that are selected by lamifudine therapy[J]. Virology, 2002, 293:305-313.
[7] Fang ZL, Yang JY, Ge XM, et al. Core promoter mutations (A1762T and G1764A) and viral genotype in chronic hepatitis B and hepatocelluiar carcinoma in Guangxi[J].China,J Med Virol, 2002, 68:33-40.
[8] YooBC, Park JW, Kim HJ, et al. Core promoter mutations of hepatitis B virus and hepatitis Be antigen-negative chronic hepatitis B in Korea[J].J Hepatol,2003,38:98-103.
[9] Sun ZT, Zhu YR, Stjemsward J, et ar. Design and complicance of HBV vaccination trial on newborns to prevent hepapocellular carcinoma and 5-year results of its pilot study[J]. Cancer detect Prev, 1991,15(4):313-318.
[10] Chen JG, Parkin DM, Chen QG, et al. Screening for liver cancer: results of a randomized controlled trial in Qidong[J]. China. Med Screen, 2003.
[11] Zhang YY, Nordenfalt Z, Hansson BG. Increasing heterogenelty of the 'a determinant of HBsAg found in the presumed late phase of chronic hepatitis B virus [J]. Stand J Infect Ois, 1996,28(1):9.
[12] Pichoud C, Berby F, Stuyver L et al. Persistence of Viral replication after anto-Hbe serconversion during antiviral therapy for chronic hepatitis B [J], J Hepatol, 2000, 32(2):30F.
[13] 张永新,杜绍财,陈苹,等.肝炎恢复期乙型肝炎表面抗体阳性者血清中的乙型肝炎病毒DNA[J].中华内科杂志,1992,31:629-632.
[14] 姚桢(编著).分子乙型肝炎病毒相关病学[M].北京:中国医药科技出版社,1998.25.
[15] 黄丹文,乙型肝炎病毒变异与临床的关系[J].浙江临床医学, 2000, 12:25-26.
[16] PollicinoT.PreS2 defective hepatitis B vires infection in patients with fulminant hepatitis[J]. Hepalology, 1997,26:495-499.
[17] Tipples GA. Mutation in HBV-DNA dependent DNA polymerase confers resistance to Lamivudine iv vivo[J]. Hepaology, 1996,24: 714-717.
[18] 尹华发,卢建溪,陈吉,等.乙肝表面抗原及抗体同时阳性的感染者[J].中国公共卫生,2001,17:621-622.
[19] Wang Y M, Ngwc, Kang Y, et al Scrological profile of Wang hepatitis B carder patients in Singapore with special reference to the frequency and signigicance of concurrent presence of HBsAg and anti-HBs[J]. Singapore Med J, 1996,37:150-152.
[20] Tang JK et al, J Pediatr,1998,133(3):374-377.
[21] 徐勇勇,陈长生.Meta分析常用统计分析方法[J].中华预防医学杂志,1994,28(5):303-305.
[22] Burk R D, Huang L Y, He GYF, et al. Outcome of perinatal hepatitis B virus exposure is dependent on maternal load [J]. J I D, 1994,170(5):1418-1421.
[23] Beasly R P, Trepo C, Stenvens C E, et al. The e antigen and vertical transmission of hepatitis B surface antigen[J]. An J Epidemol, 1977,105(2):94.
[24] Beasly R P, Prevention of perinatally transmitted hepatitis B virus infections with hepatitis B immune globulin and hepatitis B vaccine [J]. Lancet, 1983,2(8359): 1099.
[25] Guisti G ,Gaeta G B. Epidemiolgy of viral hepatitis in Italy[J]. Boll 1st sieroter Milan, 1980,59(6):571.
[26] 詹前胜,谭丽君.乙型肝炎病毒宫内传播的危险因素[J].中山医科大学学报,2001,22(1):61-63.
[27] 王清图,戴龙井,丁守生主编.消化系统疾病的新概念[M].北京,中国广播电视出版社,1993年第1版P323.
[28] 吕晴,朱启熔,段恕诚等.乙型肝炎疫苗免疫失败小儿S基因变异及临床特点研究[J].中华肝脏病杂志,1997,5(1):15.
[29] 王素萍,徐德忠,闫永平,等.用巢式PCR进行HBV宫内感染状况的研究[J].卫生研究,2000,29:23-26.
[30] 史晓红,王素萍,李淑珍,等.HBV阳性孕妇新生儿HBV感染状况的研究[J].山西医科大学学报,2004,35:18-19.
[31] Bianchi DW. Fetomaternal cell traffic,pregnancy-associated progenitor cells, and autoimmune disease[J]. Best Pratt Res Clin Obstet Gynaecol. 2004,18:959-975.
[32] Khosrotehrani K,Mery L,Aractingi S,et al.Absence of fetal cell microchimerism in cutaneous lesions of lupus erythematosus[J]. Ann Rheum Dis,2005,64:159-160.
[33] 魏俊妮,王素萍,双杰玉.母胎细胞转运与乙型肝炎病毒宫内感染关系的研究[J].中华流行病学杂志,2005,26:240-244.
[34] 余敏敏,韩国荣,沈玲.乙型肝炎病毒的母婴阻断977例1年随访研究[J].中国实用妇科与产科杂志,2004,20(9):538-540.
[35] 杨之涛.隐匿性乙型肝炎病毒感染的临床意义[J].国外医学流行病学传染病学分册,2003,30:283-286.
[2] 赵连三等.乙型肝炎病毒感染经精子传播的可能性研究[J].中华传染病杂志,1998,16(3):154-157.
[3] Tang S L,Hsu H Y, Lin H H, et al.Hepatits B surface antigenemia at birth, a long-term follow-up [J]. J Pediatr,1998,133(3),374-377.
[4] Tiollais P, etal.The hepatitis B virus[J].Nature,1985,317:489
[5] Bonino F, Importance of hepatits B virus DNA in serum and liver [J], J Hepotol, 1986,3:136.
[6] Torresi J, Earmeat-Silveim L, Deliyannis G, et al. Reduced antigenicity of the hepatitis B virus HBsAg protein arising as a consequence of sequence changes in the overlapping polymerase gene that are selected by lamifudine therapy[J]. Virology, 2002, 293:305-313.
[7] Fang ZL, Yang JY, Ge XM, et al. Core promoter mutations (A1762T and G1764A) and viral genotype in chronic hepatitis B and hepatocelluiar carcinoma in Guangxi[J].China,J Med Virol, 2002, 68:33-40.
[8] YooBC, Park JW, Kim HJ, et al. Core promoter mutations of hepatitis B virus and hepatitis Be antigen-negative chronic hepatitis B in Korea[J].J Hepatol,2003,38:98-103.
[9] Sun ZT, Zhu YR, Stjemsward J, et ar. Design and complicance of HBV vaccination trial on newborns to prevent hepapocellular carcinoma and 5-year results of its pilot study[J]. Cancer detect Prev, 1991,15(4):313-318.
[10] Chen JG, Parkin DM, Chen QG, et al. Screening for liver cancer: results of a randomized controlled trial in Qidong[J]. China. Med Screen, 2003.
[11] Zhang YY, Nordenfalt Z, Hansson BG. Increasing heterogenelty of the 'a determinant of HBsAg found in the presumed late phase of chronic hepatitis B virus [J]. Stand J Infect Ois, 1996,28(1):9.
[12] Pichoud C, Berby F, Stuyver L et al. Persistence of Viral replication after anto-Hbe serconversion during antiviral therapy for chronic hepatitis B [J], J Hepatol, 2000, 32(2):30F.
[13] 张永新,杜绍财,陈苹,等.肝炎恢复期乙型肝炎表面抗体阳性者血清中的乙型肝炎病毒DNA[J].中华内科杂志,1992,31:629-632.
[14] 姚桢(编著).分子乙型肝炎病毒相关病学[M].北京:中国医药科技出版社,1998.25.
[15] 黄丹文,乙型肝炎病毒变异与临床的关系[J].浙江临床医学, 2000, 12:25-26.
[16] PollicinoT.PreS2 defective hepatitis B vires infection in patients with fulminant hepatitis[J]. Hepalology, 1997,26:495-499.
[17] Tipples GA. Mutation in HBV-DNA dependent DNA polymerase confers resistance to Lamivudine iv vivo[J]. Hepaology, 1996,24: 714-717.
[18] 尹华发,卢建溪,陈吉,等.乙肝表面抗原及抗体同时阳性的感染者[J].中国公共卫生,2001,17:621-622.
[19] Wang Y M, Ngwc, Kang Y, et al Scrological profile of Wang hepatitis B carder patients in Singapore with special reference to the frequency and signigicance of concurrent presence of HBsAg and anti-HBs[J]. Singapore Med J, 1996,37:150-152.
[20] Tang JK et al, J Pediatr,1998,133(3):374-377.
[21] 徐勇勇,陈长生.Meta分析常用统计分析方法[J].中华预防医学杂志,1994,28(5):303-305.
[22] Burk R D, Huang L Y, He GYF, et al. Outcome of perinatal hepatitis B virus exposure is dependent on maternal load [J]. J I D, 1994,170(5):1418-1421.
[23] Beasly R P, Trepo C, Stenvens C E, et al. The e antigen and vertical transmission of hepatitis B surface antigen[J]. An J Epidemol, 1977,105(2):94.
[24] Beasly R P, Prevention of perinatally transmitted hepatitis B virus infections with hepatitis B immune globulin and hepatitis B vaccine [J]. Lancet, 1983,2(8359): 1099.
[25] Guisti G ,Gaeta G B. Epidemiolgy of viral hepatitis in Italy[J]. Boll 1st sieroter Milan, 1980,59(6):571.
[26] 詹前胜,谭丽君.乙型肝炎病毒宫内传播的危险因素[J].中山医科大学学报,2001,22(1):61-63.
[27] 王清图,戴龙井,丁守生主编.消化系统疾病的新概念[M].北京,中国广播电视出版社,1993年第1版P323.
[28] 吕晴,朱启熔,段恕诚等.乙型肝炎疫苗免疫失败小儿S基因变异及临床特点研究[J].中华肝脏病杂志,1997,5(1):15.
[29] 王素萍,徐德忠,闫永平,等.用巢式PCR进行HBV宫内感染状况的研究[J].卫生研究,2000,29:23-26.
[30] 史晓红,王素萍,李淑珍,等.HBV阳性孕妇新生儿HBV感染状况的研究[J].山西医科大学学报,2004,35:18-19.
[31] Bianchi DW. Fetomaternal cell traffic,pregnancy-associated progenitor cells, and autoimmune disease[J]. Best Pratt Res Clin Obstet Gynaecol. 2004,18:959-975.
[32] Khosrotehrani K,Mery L,Aractingi S,et al.Absence of fetal cell microchimerism in cutaneous lesions of lupus erythematosus[J]. Ann Rheum Dis,2005,64:159-160.
[33] 魏俊妮,王素萍,双杰玉.母胎细胞转运与乙型肝炎病毒宫内感染关系的研究[J].中华流行病学杂志,2005,26:240-244.
[34] 余敏敏,韩国荣,沈玲.乙型肝炎病毒的母婴阻断977例1年随访研究[J].中国实用妇科与产科杂志,2004,20(9):538-540.
[35] 杨之涛.隐匿性乙型肝炎病毒感染的临床意义[J].国外医学流行病学传染病学分册,2003,30:283-286.