HBsAg阳性母亲所分娩婴儿完成主被动免疫后的免疫保护效果及其持久性研究

Immune protection effect and persistence of passive-active immunization in infants delivered by HBsAg-positive mothers

目的明确HBsAg阳性母亲所分娩婴儿完成主被动免疫后7月龄至3岁期间的免疫保护效果与持久性。方法选取从2015年6月1日开始入组的在首都医科大学附属北京佑安医院完成了出生后主被动联合免疫[于出生后6 h内注射100 IU的乙型肝炎免疫球蛋白(hepatitis B immunoglobulin,HBIG)及接种重组酵母乙型肝炎疫苗10μg,然后在1月龄及6月龄分别注射第2次及第3次乙肝疫苗]的婴儿并进行随访,在7月龄、1岁、2岁和3岁时采用进口罗氏试剂检测乙肝5项(部分婴儿采用进口罗氏试剂检测HBV DNA定量)。结果入组婴儿550例,548例完成了出生后7个月的随访与检测,其中528例(96.4%)获得保护性抗体(HBsAb≥10 IU/L),低应答者(10 IU/L≤HBsAb<100 IU/L)有31例(5.8%)、中应答者(100 IU/L≤HBsAb<1 000 IU/L)有196例(36.6%)、高应答者(HBsAb≥1 000 IU/L)有301例(56.3%);此外,无应答者7例(1.3%),阻断失败者8例(1.5%),隐匿HBV感染者5例(0.9%)。1例7月龄时为中应答者,随访至3岁时,不但HBsAb转阴,并发生HBV再感染。随着年龄的增长,婴儿HBsAb水平逐渐下降,从7月龄至1岁的随访,528例获得保护性抗体婴儿中仅有12例(2.3%)HBsAb水平升高,其余516例(97.7%)抗体水平均下降,部分婴儿下降明显甚至转为阴性。随访至3岁时,无应答率和低应答率分别由7月龄时的1.3%和5.8%升至49.7%和27.3%,而高应答率和中应答率分别由7月龄时的56.3%和36.6%降至1.1%和21.9%。结论HBsAg阳性母亲所分娩婴儿7月龄至3岁的HBsAb水平不同,呈动态变化;随着年龄的增长,大部分婴儿HBsAb水平下降,随访至3岁时,更多的婴儿抗体水平下降至低应答水平或转为阴性,甚至发生再感染;建议HBsAg阳性母亲所分娩的婴儿在出生后7个月至3年进行积极随访监测,可有效发现处于无应答、低应答状态者,及时采取加强或再次免疫措施,防止此类高危人群出生后再次感染HBV。

Objective To confirm the immune protection effects and persistence of infants delivered by mothers with hepatitis B surface antigen(HBsAg)positive from seven months to three years old after passive-active immunization.Methods Infants who completed passive-active immunization after birth(injecting 100 IU of hepatitis B immunoglobulin and 10μg of recombinant yeast hepatitis B vaccine within six hours after birth,and then injecting the 2 nd and 3 rd hepatitis B vaccines at one month and six months respectively)were enrolled from June 1 st,2015 and followed up.Five serological markers of hepatitis B were tested at the age of seven months,one year,two years and three years old with Roche reagent(some infants were tested for HBV DNA by using imported Roche reagent).Results A total of 550 infants were enrolled in the study,548 patients completed follow-up and were tested at seven months of age,of whom 528(96.4%)received protective antibodies(anti-HBs≥10 IU/L),and low responders(10 IU/L≤anti-HBs<100 IU/L)was 31(5.8%),medium responders(100 IU/L≤antiHBs<1 000 IU/L)were 196(36.6%),high responders(anti-HBs≥1 000 IU/L)301 cases(56.3%);in addition,seven infants(1.3%)were non-responders,8(1.5%)infants became HBV infection and five infants(0.9%)became occult HBV infected.For one infant who was a medium responder at seven months of age,when followed up to three years old,not only anti-HBs were negative,but HBV reinfection occurred.Anti-HBs levels of infants gradually decreased from seven months age to one year old.At follow-up,only 12 infants’(2.3%)anti-HBs levels were elevated,and the remaining 516 infants’(97.7%)antibody levels decreased,and some infants decreased significantly or even became negative.When followed up to three years old,the no response rate and low response rate increased from 1.3%and 5.8%at seven months of age to 49.7%and 27.3%at three years old,while the high and medium response rates were reduced from 56.3%and 36.6%at seven months of age to1.1%and 21.9%at three years old.Conclusions Levels of anti-HBs in infants from seven months to three years were different,which showed dynamic changes.Some infants had decreased anti-HBs levels.When they were three years old,more infant antibody levels fell to low response level or became negative.It is recommended that infants delivered by HBsAg-positive mothers should be actively followed up for seven months to three years after birth.It can effectively detect those who are in a state of non-responders or low-responders,and timely immunization measures can be taken to prevent HBV reinfection in high-risk groups.