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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HBIG 200~400 U(HBsAg阳性者注射HBIG 200 U、HBsAg和HBeAg双阳性者注射HBIG 400 U);HBIG B组:29例孕妇于产前3、2、1妊娠月分别肌肉注射HBIG 200 U;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);HBIG B组7例新生儿有5例宫内感染,但差异无统计学意义(χ~2=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。
Objective To evaluate the efficacy of different regimens of hepatitis B immunoglobulin (HBIG) in preventing intrauterine infection of HBV and to explore its mechanism of action and its influence on virus mutation. Methods Asymptomatic HBV-carrying pregnant women and their newborn infants were studied. Asymptomatic HBV-carrying pregnant women were randomly divided into HBIG group A during antenatal examination. Twenty-six pregnant women were assigned to prenatal months 3, Intramuscular injection of HBIG 200 ~ 400 U (HBsAg positive injection of HBIG 200 U, HBsAg and HBeAg double positive HBIG injection of 400 U); HBIG B group: 29 cases of pregnant women in the prenatal 3,2,1 month of gestation, intramuscular injection of HBIG200 U; control group: 26 pregnant women did not receive any special prenatal treatment. All the 3 groups were given the blood samples before and after HBIG and the blood samples before and after HBIG on the day of labor, and the newborns were taken before the combined immunization. HBV markers were detected by enzyme immunoassay (EIA) Quantitative polymerase chain reaction (FQ-PCR) detection of HBV DNA and PCR amplification of HBV DNA S gene region fragment and sequencing. Results 55 newborns were born to mothers of HBIG group (A and B). The intrauterine infection rate was 14.5% and that of the control group was 35.7% (χ ~ 2 = 4.896, P = 0.027). Among 8 neonates born HBsAg and HBeAg double positive mothers in HBIG group, 3 had intrauterine infection, and 8 neonates in the control group had intrauterine infection (χ ~ 2 = 7.273, P = 0.007). There were 5 intrauterine infection in 7 neonates with HBIG B group, but the difference was not statistically significant (χ ~ 2 = 2.637, P = 0.104). The serum levels of HBsAg in the third trimester pregnant women were comparable to those of HBV DNA, but the levels of HBsAg and HBV DNA in pregnant women before HBIG were lower than those in HBIG B and control groups. HBIG A neonatal serum anti-HBs detection rate was 38.5%. No anti-HBs were detected in all three groups before delivery. There was no significant difference in mutation rate of base substitution and amino acid variation in HBV S region between HBIG group (A and B) and control group. In 18 cases of intrauterine infection, there was no significant difference in the mutation rate of amino acid substitutions and amino acid between the HBIG group (A and B) and the control group. Conclusions The prenatal injection of HBIG in pregnant women has positive effect of blocking the transmission of HBV from mother to child, and the two different doses of HBIG are used according to the different states of HBV carrying. The addition of HBIG before childbirth is more effective. The passive immunization of the fetus through the placenta is HBIG Important mechanism of action; asymptomatic HBV carriers prenatal HBIG did not increase HBV S District mutation, HBV S District mutation is not the main cause of intrauterine infection.