免疫阻断乙型肝炎病毒母婴传播多中心研究
|
摘要
目的探讨孕产妇乙型肝炎表面抗原(HBs Ag)阳性率及乙型肝炎病毒(HBV)母婴传播阻断的效果。方法2008-2012年,通过多中心队列研究,对湖北省、山西省、广东省、新疆维吾尔自治区等地的孕产妇进行HBs Ag筛查;对上述地区部分医院入院分娩的HBs Ag阳性母亲及8~12个月龄婴儿进行随访观察,所有标本检测乙型肝炎血清标志物(HBs Ag,HBs Ab,HBe Ag,HBe Ab,HBc Ab),部分标本检测HBV DNA。结果筛查孕妇82214例,HBs Ag阳性4924例,阳性率6.0%。随访HBs Ag阳性母亲及8~12个月龄婴儿1371对,婴儿免疫阻断失败率3.1%(42/1371),HBs Ag及HBe Ag双阳性母亲婴儿的免疫阻断失败率为8.2%。免疫阻断失败的婴儿其母亲均为HBe Ag阳性且HBV DNA≥6 log10copies/m L。HBe Ag阳性母亲孕期注射乙型肝炎免疫球蛋白(hepatitis B immune globulin,HBIG)及未注射HBIG组,其婴儿免疫阻断失败率差异无统计学意义(8.8%vs.8.1%,P=0.807)。结论多中心调查显示目前孕产妇HBs Ag阳性率6.0%,HBV母婴阻断失败率3.1%。HBs Ag及HBe Ag双阳性且HBV DNA≥6 log10 copies/m L的孕妇应为母婴阻断的重点人群。孕妇孕期注射HBIG不能提高HBV母婴阻断效果。
Objective To evaluate the current positive rete of HBs Ag among pregnant women and explore more effective interruption measures for mother- to- infant transmission.Methods From 2008 to 2012, pregnant women were screened for HBs Ag in multi-centers(Province of Hubei, Shanxi and Guangdong and Xinjiang Uygur Autonomous Region). HBs Ag positive mothers before labour and their infants aged 8~12 months in some hospitals among those areas were determined for HBV markers(HBs Ag,HBs Ab,HBe Ag,HBe Ab,HBc Ab) and some of them also had HBV DNA tests.Results HBs Ag positive rate of pregnant women was 6.0%(4924/82214). Infants' immunoprophylaxis failure rate was 3.1%(42/1371) and it was 8.2% among infants of HBs Ag and HBe Ag positive mothers. Immunoprophylaxis failure infants were all born to mothers of HBe Ag positive and HBV DNA ≥6 log10copies/m L. Among infants of HBe Ag positive mothers, immunoprophylaxis failure rates had no significant difference between mother with hepatitis B immune globulin(HBIG) and without HBIG(8.8% vs. 8.1%, P=0.807).Conclusions These findings demonstrate that pregnant women are still with high HBs Ag prevalence(6.0%) in China.HBV mother-to-infant transmission(3.1%) still occurs after active-passive immunization. Pregnant women of HBs Ag and HBe Ag positive and HBV DNA≥6 log10copies/m L are the major population for preventing HBV mother- to-infant transmission. HBIG administered during late pregnancy to HBs Ag-positive mothers does not reduce the risk of mother-to-child transmission of HBV.
Objective To evaluate the current positive rete of HBs Ag among pregnant women and explore more effective interruption measures for mother- to- infant transmission.Methods From 2008 to 2012, pregnant women were screened for HBs Ag in multi-centers(Province of Hubei, Shanxi and Guangdong and Xinjiang Uygur Autonomous Region). HBs Ag positive mothers before labour and their infants aged 8~12 months in some hospitals among those areas were determined for HBV markers(HBs Ag,HBs Ab,HBe Ag,HBe Ab,HBc Ab) and some of them also had HBV DNA tests.Results HBs Ag positive rate of pregnant women was 6.0%(4924/82214). Infants' immunoprophylaxis failure rate was 3.1%(42/1371) and it was 8.2% among infants of HBs Ag and HBe Ag positive mothers. Immunoprophylaxis failure infants were all born to mothers of HBe Ag positive and HBV DNA ≥6 log10copies/m L. Among infants of HBe Ag positive mothers, immunoprophylaxis failure rates had no significant difference between mother with hepatitis B immune globulin(HBIG) and without HBIG(8.8% vs. 8.1%, P=0.807).Conclusions These findings demonstrate that pregnant women are still with high HBs Ag prevalence(6.0%) in China.HBV mother-to-infant transmission(3.1%) still occurs after active-passive immunization. Pregnant women of HBs Ag and HBe Ag positive and HBV DNA≥6 log10copies/m L are the major population for preventing HBV mother- to-infant transmission. HBIG administered during late pregnancy to HBs Ag-positive mothers does not reduce the risk of mother-to-child transmission of HBV.
引文
[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]Luo Z,Li L,Ruan B.Impact of the implementation of a vaccination strategy on hepatitis B virus infections in China over a 20-year period[J].Int J Infect Di,s,2012,16(2):e82-88.
[3]Shi Z,Li X,Ma L,et al.Hepatitis B immunoglobulin injection in pregnancy to interrupt hepatitis B virus mother-to-child transmission-a meta-analysis[J].Int J Infect Dis,2010,14(7):e622-634.
[4]Yin Y,Wu L,Zhang J,et al.Identification of risk factors associated with immunoprophylaxis failure to prevent the vertical transmission of hepatitis B virus[J].J Infect,2013,66(5):447-452.
[5]Peng X.China's demographic history and future challenges[J].Science,2011,333(6042):581-587.
[6]Merrill RM,Hunter BD.Seroprevalence of markers for hepatitis B viral infection[J].Int J Infect Dis,2011,15(2):e78-121.
[7]Panda SK,Gupta A,Datta R,et al.Transplacental transmission of hepatitis B virus[J].Lancet,1986,2(8512):919-920.
[8]Beasley RP,Trepo C,Stevens CE,et al.The e antigen and vertical transmission of hepatitis B surface antigen[J].Am J Epidemiol,1977,105(2):94-98.
[9]Elefsiniotis IS,Tsoumakas K,Papadakis M,et al.Importance of maternal and cord blood viremia in pregnant women with chronic hepatitis B virus infection[J].Eur J Intern Med,2011,22(2):182-186.
[10]Wong VC,Ip HM,Reesink HW,et al.Prevention of the HBs Ag carrier state in newborn infants of mothers who are chronic carriers of HBs Ag and HBe Ag by administration of hepatitis-B vaccine and hepatitis-B immunoglobulin:double-blind randomised placebo-controlled study[J].Lancet,1984,1(8383):921-926.
[11]Wong VC,Lee AK,Ip HM.Transmission of hepatitis B antigens from symptom free carrier mothers to the fetus and the infant[J].Br J Obstet Gynaecol,1980,87(11):958-965.
[12]Lee AK,Ip HM,Wong VC.Mechanisms of maternal-fetal transmission of hepatitis B virus[J].J Infect Dis,1978,138(5):668-671.
[13]Zou H,Chen Y,Duan Z,et al.Virologic factors associated with failure to passive-active immunoprophylaxis in infants born to HBs Ag-positive mothers[J].J Viral Hepat,2012,19(2):e18-25.
[14]Ying HM,Lelie PN,Wong VC,et al.Prevention of hepatitis B virus carrier state in infants according to maternal serum levels of HBV DNA[J].Lancet,1989,1(8635):406-410.
[15]Wiseman E,Fraser MA,Holden S,et al.Perinatal transmission of hepatitis B virus:an Australian experience[J].Med J Aust,2009,190(9):489-492.
[16]Hahne S,van den Hoek A,Baayen D,et al.Prevention of perinatal hepatitis B virus transmission in the Netherlands,2003-2007:children of Chinese mothers are at increased risk of breakthrough infection[J].Vaccine,2012,30(9):1715-1720.
[17]Song YM,Sung J,Yang S,et al.Factors associated with immunoprophylaxis failure against vertical transmission of hepatitis B virus[J].Eur J Pediatr,2007,166(8):813-818.
[18]Li XM,Shi MF,Yang YB,et al.Effect of hepatitis B immunoglobulin on interruption of HBV intrauterine infection[J].World J Gastroenterol,2004,10(21):3215-3217.
[19]朱启镕,吕晴,顾新焕,等.阻断乙型肝炎病毒宫内传播的初步研究[J].中华儿科杂志,1995,33(2):93-95+126-127.
[20]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.
[21]Lok AS,Heathcote EJ,Hoofnagle JH.Management of hepatitis B:2000--summary of a workshop[J].Gastroenterology,2001,120(7):1828-1853.
[22]Liaw YF,Leung N,Guan R,et al.Asian-Pacific consensus statement on the management of chronic hepatitis B:a 2005 update[J].Liver Int,2005,25(3):472-489.
[23]孙玉革,庄辉,韩忠厚,等.孕晚期注射乙肝免疫球蛋白对乙型肝炎病毒母婴传播阻断率影响的探讨[J].中华实验和临床感染病杂志(电子版),2007,1(3):155-157.
[24]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(2010年版)[J].中华传染病杂志,2011,29(2):65-80.
[25]夏国良,龚健,王继杰,等.重组乙型肝炎疫苗阻断乙型肝炎病毒母婴传播方案的保护效果评价[J].中华流行病学杂志,2003,24(5):362-365.
[26]Shao ZJ,Zhang L,Xu JQ,et al.Mother-to-infant transmission of hepatitis B virus:a Chinese experience[J].J Med Virol,2011,83(5):791-795.
[2]Luo Z,Li L,Ruan B.Impact of the implementation of a vaccination strategy on hepatitis B virus infections in China over a 20-year period[J].Int J Infect Di,s,2012,16(2):e82-88.
[3]Shi Z,Li X,Ma L,et al.Hepatitis B immunoglobulin injection in pregnancy to interrupt hepatitis B virus mother-to-child transmission-a meta-analysis[J].Int J Infect Dis,2010,14(7):e622-634.
[4]Yin Y,Wu L,Zhang J,et al.Identification of risk factors associated with immunoprophylaxis failure to prevent the vertical transmission of hepatitis B virus[J].J Infect,2013,66(5):447-452.
[5]Peng X.China's demographic history and future challenges[J].Science,2011,333(6042):581-587.
[6]Merrill RM,Hunter BD.Seroprevalence of markers for hepatitis B viral infection[J].Int J Infect Dis,2011,15(2):e78-121.
[7]Panda SK,Gupta A,Datta R,et al.Transplacental transmission of hepatitis B virus[J].Lancet,1986,2(8512):919-920.
[8]Beasley RP,Trepo C,Stevens CE,et al.The e antigen and vertical transmission of hepatitis B surface antigen[J].Am J Epidemiol,1977,105(2):94-98.
[9]Elefsiniotis IS,Tsoumakas K,Papadakis M,et al.Importance of maternal and cord blood viremia in pregnant women with chronic hepatitis B virus infection[J].Eur J Intern Med,2011,22(2):182-186.
[10]Wong VC,Ip HM,Reesink HW,et al.Prevention of the HBs Ag carrier state in newborn infants of mothers who are chronic carriers of HBs Ag and HBe Ag by administration of hepatitis-B vaccine and hepatitis-B immunoglobulin:double-blind randomised placebo-controlled study[J].Lancet,1984,1(8383):921-926.
[11]Wong VC,Lee AK,Ip HM.Transmission of hepatitis B antigens from symptom free carrier mothers to the fetus and the infant[J].Br J Obstet Gynaecol,1980,87(11):958-965.
[12]Lee AK,Ip HM,Wong VC.Mechanisms of maternal-fetal transmission of hepatitis B virus[J].J Infect Dis,1978,138(5):668-671.
[13]Zou H,Chen Y,Duan Z,et al.Virologic factors associated with failure to passive-active immunoprophylaxis in infants born to HBs Ag-positive mothers[J].J Viral Hepat,2012,19(2):e18-25.
[14]Ying HM,Lelie PN,Wong VC,et al.Prevention of hepatitis B virus carrier state in infants according to maternal serum levels of HBV DNA[J].Lancet,1989,1(8635):406-410.
[15]Wiseman E,Fraser MA,Holden S,et al.Perinatal transmission of hepatitis B virus:an Australian experience[J].Med J Aust,2009,190(9):489-492.
[16]Hahne S,van den Hoek A,Baayen D,et al.Prevention of perinatal hepatitis B virus transmission in the Netherlands,2003-2007:children of Chinese mothers are at increased risk of breakthrough infection[J].Vaccine,2012,30(9):1715-1720.
[17]Song YM,Sung J,Yang S,et al.Factors associated with immunoprophylaxis failure against vertical transmission of hepatitis B virus[J].Eur J Pediatr,2007,166(8):813-818.
[18]Li XM,Shi MF,Yang YB,et al.Effect of hepatitis B immunoglobulin on interruption of HBV intrauterine infection[J].World J Gastroenterol,2004,10(21):3215-3217.
[19]朱启镕,吕晴,顾新焕,等.阻断乙型肝炎病毒宫内传播的初步研究[J].中华儿科杂志,1995,33(2):93-95+126-127.
[20]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.
[21]Lok AS,Heathcote EJ,Hoofnagle JH.Management of hepatitis B:2000--summary of a workshop[J].Gastroenterology,2001,120(7):1828-1853.
[22]Liaw YF,Leung N,Guan R,et al.Asian-Pacific consensus statement on the management of chronic hepatitis B:a 2005 update[J].Liver Int,2005,25(3):472-489.
[23]孙玉革,庄辉,韩忠厚,等.孕晚期注射乙肝免疫球蛋白对乙型肝炎病毒母婴传播阻断率影响的探讨[J].中华实验和临床感染病杂志(电子版),2007,1(3):155-157.
[24]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(2010年版)[J].中华传染病杂志,2011,29(2):65-80.
[25]夏国良,龚健,王继杰,等.重组乙型肝炎疫苗阻断乙型肝炎病毒母婴传播方案的保护效果评价[J].中华流行病学杂志,2003,24(5):362-365.
[26]Shao ZJ,Zhang L,Xu JQ,et al.Mother-to-infant transmission of hepatitis B virus:a Chinese experience[J].J Med Virol,2011,83(5):791-795.