乙型肝炎病毒母婴传播产前免疫阻断的研究

目的评价不同方案乙型肝炎免疫球蛋白（HBIG）预防HBV宫内感染的疗效，探讨其作用机制，并了解其对病毒变异的影响。方法以无症状HBV携带孕妇及其新生婴儿为研究对象，将无症状HBV携带孕妇在产前检查时随机分为HBIG A组：26例孕妇于产前3、2、1妊娠月和分娩前分别肌肉注射HBIG200～400U（HBsAg阳性者注射HBIG200U、HBsAg和HBeAg双阳性者注射HBIG400U）；HBIG B组：29例孕妇于产前3、2、1妊娠月分别肌肉注射HBIG200U；对照组：26例孕妇产前未接受任何特殊治疗。3组均留取孕中期产检时（应用HBIG前）和临产日使用HBIG前后的静脉血标本，新生儿于生后联合免疫前留取外周血，酶免疫测定法（EIA）检测HBV标志，荧光定量聚合酶链反应（FQ-PCR）检测HBV DNA以及PCR扩增HBV DNA S基因区片段并测序。结果55例新生儿为HBIG组（A和B）母亲所生，宫内感染率为14．5％，对照组为35．7％（χ^2=4．896，P=0．027）。HBIG A组HBsAg和HBeAg双阳性母亲所生的8例新生儿有3例宫内感染，对照组8例新生儿均有宫内感染（χ^2=7．273，P=0．007）；HBIGB组7例新生儿有5例宫内感染，但差异无统计学意义（χ=2．637，P=0．104）。3组孕妇孕中期血清HBsAg与HBV DNA水平相当，但分娩前HBIG A组孕妇HBsAg及HBV DNA均低于HBIG B组和对照组。HBIG A组新生儿血清抗-HBs检出率为38．5％。3组产妇分娩前均未检测到抗-HBs。HBV S区碱基替代突变率和氨基酸变异数在HBIG组（A和B）和对照组之间差异均无统计学意义。18例宫内感染儿，HBV S区碱基替代突变率和氨基酸变异数在HBIG组（A和B）和对照组之间差异均无统计学意义。结论孕妇产前注射HBIG阻断HBV母婴传播的免疫效果肯定，按HBV携带不同状态使用两种不同剂量HBIG，并于分娩前加用一次，效果更佳；经胎盘使胎儿获得被动免疫是HBIG重要作用机制；无症状携带HBV孕妇产前使用HBIG并未增加HBV S区的变异，HBV S区变异并非是发生宫内感染的主要原因。

Study on a antepartum immunoprophylaxis to interrupt the transmission of hepatitis B virus from mother to infant

Objective To investigate the efficacy and the mechanism of different dose hepatitis B immunoglohulin(HBIG)on prevention of HBV intrauterine infection and HBV S gene mutation. Methods HBV carrier mothers were randomly divided into three groups.Eighty-one HBsAg carrier pregnant women were divided into HBIG A group.HBIG B group and control group.Each subject in the HBIG A group received 200 U or 400 U(for HBsAg and HBeAg double positive carrier)intra muscularly at 3,2,1 month before delivery.Each subject in the HBIG B group received 200 U intra muscularly at 3,2,1 month before delivery.The subjects in the control group did not receive any treatment.Maternal blood samples were taken before HBIG injection and at delivery.Neonatal blood samples of all newborn infants after birth were taken before immunopropbylaxis.Their sera were ob tained to test HBV markers by enzyme immunoassay(EIA)and HBV DNA by fluorescence quantita- tive polymerase chain reaction(FQ-PCR),then to amplify and sequence HBV S gene region.Results The rate of HBV intrauterine infection in the HBIG group(14.5%)was lower than that in the control group(35.7%)(X~2=4.896,P=0.027).The rate of HBV intrauterine infection of newborns from HBsAg and HBeAg double positive carrier mother in the HBIG A group(37.5%)were lower than control group(100.0%)(X~2=7.273,P=0.007),while the rate was no different in the HBIG B group(71.5%)and the control group(X~2=2.637,P=0.104).Maternal HBsAg titer and HBV DNA level were of no difference among three groups before HBIG injection.Maternal HBsAg titers and HBV DNA levels of the HBIG A group were lower than those of the HBIG B group and the con- trol group at delivery.Among the 26 neonatal serum samples in the HBIG A group,10(38.5%)were positive for anti-HBs,while in the HBIG B group and in the control group,no neonatal serum sam- ples was positive.There was no significant difference of nucleotide and amino acid changes in the S gene between the HBIG group and the control group.Conclusions HBV infection in the uterus may be interrupted by injection HBIG intramuscularly before delivery.More efficacy would be found using variable HBIG dose according to different HBV virema and must be once more again injected just he- fore one week of delivery;anti-HBs transported to the fetus via the placenta and it's may be the im- portant mechanism of HBIG prevention.Asymptomatic HBsAg carrier mother received injections of HBIG before delivery should not influence HBV S gene mutation.Gene mutation of HBV is not the main factor in intrauterine transmission of HBV.