HBsAg阳性母亲其婴幼儿免疫阻断后无/低应答危险因素及个体化免疫干预效果分析

Risk factors and individual immunologic intervention of non-or low-response status in infants of HBsAg positive mothers after hepatitis B vaccination

目的探讨HBsAg阳性母亲其婴幼儿免疫阻断后无/低应答的危险因素,以及个体化免疫干预的效果。方法选取2011年8月至2013年1月于本院出生母亲HBsAg阳性的婴幼儿144例,根据完成3次乙肝疫苗免疫计划后,即婴儿7月龄时的HBsAb水平,分为无/低应答组(53例)和正常应答组(91例)。分析两组母亲孕早期HBVDNA水平、HBV标志物(HBsAg、HBsAb、HBe Ag、HBe Ab和HBc Ab),婴儿出生史、喂养史以及出生后HBV标志物等,分析婴儿无/低应答的危险因素。选取乙肝疫苗全程免疫计划结束后无/低应答婴儿50例,正常应答婴儿50例作为对照组,对无/低应答婴儿进行个体化免疫干预,18月龄时比较两组患儿应答状态。结果 Logistic回归分析显示,早产儿、低出生体重儿、未按时添加蛋白质类辅食、未注射乙肝免疫球蛋白的儿童发生无/低应答的风险分别是正常儿童的25.51倍(Waldχ2=12.45)、20.54倍(Waldχ2=14.59)、28.47倍(Waldχ2=15.36)和16.67倍(Waldχ2=19.09)(P均<0.001),母亲孕期e抗原、核心抗体是独立的危险因素,每增加1个单位,发生免疫不应答的风险分别增加1.001(Waldχ2=3.97)和1.16倍(Waldχ2=4.45)(P均<0.05)。通过个体化免疫干预治疗,18个月龄时,83.3%的低应答儿和70.0%的无应答儿获得正常应答,与正常应答组差异无统计学意义(χ2=2.84、P=0.12;χ2=2.32、P=0.15),干预后低应答组的表面抗体水平与正常应答组差异无统计学意义(t=1.22、P=0.61),而无应答组抗体水平仍较正常组偏低(t=2.43、P=0.02)。与干预前相比,无应答组和低应答组的抗体水平均显著增高(t=2.54、P=0.02;t=2.76、P=0.01)。结论母亲孕期高水平HBe Ag、HBc Ab,早产儿、低出生体重儿、未按时添加蛋白质类辅食、未注射第2次乙肝免疫球蛋白是发生乙肝免疫无/低应答的危险因素。个体化免疫干预可有效提高免疫应答率,提高HBsAb水平,降低感染HBV的风险。

Objective To identify the risk factors for non/low response to hepatitis B vaccinations in infants of hepatitis B surface antigen （HBsAg）-positive mothers and to evaluate the effects of subsequent individualized immune intervention in these infants. Methods Total of 144 infants of HBsAg-positive mothers enrolled in our hospital from August 2011 to January 2013, that had completed an immunization program of three-dose hepatitis B vaccines, were recruited. The risk factors for the non- or low-immune response to hepatitis B vaccinations were analyzed. Infants of the non-/low-immune response group were subsequently administered individualized immune interventions, following by reevaluation of immune responses to hepatitis B vaccinations at 18 months of age. Results Logistic regression showed that the risk of the non- or low-immune response to＆amp;nbsp;hepatitis B vaccinations in infants with preterm delivery, low birth weight of the infants, late administration of protein supplements, and failure to receive the second dose of hepatitis B immunoglobulin （HBIG） during neonatal days 15-30 increased 25.51, 20.54, 28.47 and 16.67 times than normal children, and the value of Waldχ2 were 12.45, 14.59, 15.36 and 10.09, respectively （all P 〈 0.001）. The risk increased 1.001 （Wald χ2 = 3.97） and 1.16 times （Wald χ2 = 4.45） when HBeAg and HBcAb in the mother during early pregnancy increased one unit （all P 〈 0.05）. Moreover, 83.3% of low-immune response infants and 70.0% of non-immune response infants achieved normal-immune response at 18 months, and had no statistic significance with normal-immune response infants （χ2 = 2.84, P = 0.12; χ2 = 2.32, P = 0.15）, and the HBsAb levels were significantly elevated after individualized immune interventions （t = 2.54, P = 0.02; t = 2.76, P = 0.01）. Conclusions High HBeAg and HBcAb levels of the mothers during early pregnancy, preterm delivery, low birth weight of the infants, late administration of protein supplements, and failure to receive second HBIG injection in the infants were the risk factors for non- or low-immune response. Individualized immune intervention effectively enhanced the immune response and alleviated the risk of HBV infection in the infants.