HBsAg阳性母亲所生婴儿联合免疫后乙型肝炎表面抗体的动态变化

Combined immunoprophylaxis induces changes in anti-hepatitis B surface protein liter in infants born to mothers with post for hepatitis B surface antigen

目的通过前瞻性随机对照观察HBsAg阳性母亲所生婴儿接受联合免疫（乙肝免疫球蛋白联合5μg或10μg重组酵母乙型肝炎疫苗）后乙型肝炎表面抗体（抗-HBs）滴度的动态变化，比较不同剂量乙型肝炎疫苗免疫效果的差异，为更好地建立此类高危人群的免疫策略、监测模式及加强免疫提供基础。方法对269例HBsAg阳性母亲的婴儿于出生后12h内进行联合免疫（乙型肝炎免疫球蛋白200IU，重组酵母乙型肝炎疫苗随机分为5μg和10μg），并在出生时、1、7、12月龄进行HBVDNA载量，HBsAg及抗-HBs滴度的动态监测。根据资料不同运用秩和检验、z。检验及Fisher精确概率法进行统计学分析。结果（1）HBsAg阳性母亲的婴儿出生后联合免疫一年保护率可达到95．9％。接受不同剂量疫苗免疫婴儿中，HBV感染率没有明显差别（x2=0．876，P=0．377）。（2）动态监测未感染婴儿1月龄抗-HBs平均滴度为144．1mIU／ml，7月龄达最高581．8mIU／ml，12月龄降至397．6mIU／ml；7月龄抗-HBs滴度小于100mIU／ml的比例为20．9％，小于10mIU／ml的比例为7．4％（无／弱应答率）；12月龄抗-HBs滴度小于100mIU／ml的比例升至30．20／0，小于10mIU／ml的比例则上升至15．9％。（3）7月龄时，10μg疫苗组婴儿抗-HBs平均滴度高于5ug组（675．3mIU／ml对比425．0mIU／ml，P=0．001），无／弱应答率显著低于5μg组（2．3％对比12．60／0，P=0．002）;12月龄时，10μg疫苗组婴儿抗-HBs滴度小于100mIU／ml的比例明显低于5μg组（20．60／0对比40．20／0，P=0．001）。结论虽然HBsAg阳性母亲所生婴儿联合免疫1年时的保护率可达95．9％，但仍有30．2％的婴儿此时抗-HBs滴度已降至100mIU／ml以下，保护性下降，规律监测可有效发现处于无、低应答状态者，及时采取加强免疫措施可防止此类高危人群后期HBV水平传播;联合免疫中，10Hg重组酞母乙型肝炎疫苗在产生抗-HBs滴度水平及降低无、低应答率方面均优于5μg，应将10μg乙型肝炎疫苗纳入HBsAg阳性母亲所生婴儿的计划免疫。

Objective To conduct a prospective randomized controlled trial of infants born to hepatitis B virus （HBV） surface antigen （HBsAg）-positive mothers in order to investigate the dynamic changes in the titer of anti-HBV surface protein （HBS） induced by treatment with combinedimmunoprophylaxis （200 IU hepatitis B immunoglobulin （HBIG） and 5 or 10 μg yeast recombinant hepatitis B vaccine）, to compare the protective effect of 5 and 10 μg hepatitis B vaccine, and to provide an immunization strategy, monitoring mode and booster immunization schedule for the high-risk group. Methods Two-hundred-and-sixty-nine infants born to HBsAg positive mothers were given combined immunoprophylaxis at birth, and the venous blood samples （at birth, and 1, 7 and 12 months） were tested for HBV DNA load, and HBsAg and anti-HBS titers. Results The overall 1-year protective rate of combined immunoprophylaxis was 95.9%. There was no significant difference between the infectious rates of infants given the 5 μg or the 10 μg hepatitis B vaccine （x2 = 0.876,P = 0.377）. The geometric mean titers （GMTs） of anti-HBS were 144.1 mIU/ml at 1-month old and 564.9 mIU/ml at the age of 7 months old （the highest point）, but declined to 397.6 mIU/ml at the age of 12 months old. The rate of infants with anti-HBS titer 〈 100 mIU/ml was 20.9%, and that of 〈 10 mIU/ml was 7.4% at 7-month-old; the rate of infants with anti-HBS titer 〈 100 mIU/ml increased to 30.2% and that of〈 10 mIU/ml increased to 15.9% at 12-month- old. At 7-month-old, the GMT of the 10 μg vaccine group was higher than that of the 5μg vaccine group （675.3 mIU/ml vs. 25.0 mIU/ml, P = 0.001） and the rate of infants with anti-HBS titer 〈 10 mIU/ml was significantly lower in the 10 μg vaccine group （2.3% vs. 12.6%, P = 0.002）; at 12-month-old, the rate of infants with anti-HBS titer 〈 100 mIU/ml was also significantly lower in the 10 μg group （20.6% vs. 40.2%, P = 0.001）. Conclusion Combined immunoprophylaxis is therapeutically efficacious for treating infants bom to HBsAg positive mothers. Monitoring these infants＇ anti-HBs titer will help to identify non- or low-responders in a timely manner. The high-dose hepatitis B vaccine is preferable to the low-dose, and should be considered for use in immunization strategies for these infants.