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摘要：
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摘要：目的 探讨乙型肝炎病毒（hepatitis B virus，HBV）感染母亲所生儿童3岁时的乙
肝疫苗免疫应答情况及其影响因素。方法 以2017年1月1日至2018年5月1日于首都医科
大学附属北京地坛医院产检并分娩的HBV感染孕妇及其分娩的婴儿为研究对象，婴儿
完成规范的乙肝疫苗接种及乙肝免疫球蛋白注射，并对婴儿随访至3岁。1岁及3岁时
检测婴儿乙型肝炎病毒表面抗原（hepatitis B virus surface antigen，HBsAg）、乙型肝
炎病毒表面抗体（hepatitis B virus surface antibody，HBsAb）滴度、肝功能及血红蛋白
等，通过医院HIS系统和LIS系统收集孕妇孕产期临床生物化学指标、HBV DNA、孕期
抗病毒治疗情况及孕产期并发症等。按儿童3岁时HBsAb水平将母亲及儿童分为无/弱
应答组（HBsAb ＜ 100 mIU/ml）和强应答组（HBsAb ≥ 100 mIU/ml）。采用Logistic
回归分析3岁儿童对乙肝疫苗免疫应答的影响因素。结果 共纳入符合条件的HBV感染
孕妇及其分娩婴儿各155例，孕期未应用抗病毒药物行母婴阻断者39例，用药者116例
（其中拉米夫定30例，替比夫定86例），用药组孕中期（用药前）HBV DNA为（7.35 ±
0.57）lg IU/ml，未用药组孕中期HBV DNA为（7.26 ± 0.71）lg IU/ml，差异无统计学意义
（t = -0.856，P = 0.393）；用药组分娩前HBV DNA为（3.69 ± 0.88）lgIU/ml，未用药组分
娩前HBV DNA为（6.77 ± 1.22）lgIU/ml，差异有统计学意义（t = 17.04，P ＜ 0.001）。
23例儿童出生后7个月～3岁曾补种乙肝疫苗，3岁时HBsAb中位滴度为208.84 mIU/ml；
132例未补种，3岁时HBsAb中位滴度为94.07 mIU/ml，较1岁时（370.66 mIU/ml）显
著降低（z = -0.607，P ＜ 0.001），补种疫苗儿童3岁时HBsAb滴度显著高于未补种疫
苗儿童（z = -2.402，P = 0.016）。未补种乙肝疫苗儿童1岁时乙肝疫苗无/弱应答率为
25.75%（34/132），3岁时无/弱应答率为51.52%（68/132），补种乙肝疫苗儿童3岁时
无/弱应答率为21.74%（5/23）。155例母婴阻断成功儿童至3岁时无1例感染HBV。多因
素Logistic回归分析表明补种乙肝疫苗是3岁儿童乙肝免疫应答效果的独立保护因素
（OR = 0.259，95%CI：0.09～0.741，P = 0.012）。结论 孕期应用乙型肝炎抗病毒药物
可显著降低HBV DNA水平，不影响婴儿对乙肝疫苗的免疫应答，补种乙肝疫苗是3岁
儿童乙肝疫苗免疫应答效果的独立保护因素。
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Abstract: Objective To investigate the immune response and influencing factor of hepatitis
B virus vaccine on 3-year-old children born to mothers infected with hepatitis B virus (HBV).
Methods HBV-infected pregnant women and their babies delivered in Beijing Ditan Hospital,
Capital Medical University from January 1st, 2017 to May 1st, 2018 were collected. The
infants received standard hepatitis B virus vaccine and immunoglobulin injection, and were
followed up to 3 years old. Hepatitis B virus surface antigen (HBsAg), hepatitis B virus
surface antibody (HBsAb) titer, liver function and hemoglobin of the infants were detected at
1 year and 3 years old. Clinical biochemical indexes, HBV DNA, antiviral treatment during
pregnancy and complications were collected through HIS system and LIS system. Mothers
and children were divided into no/weak response group (HBsAb ＜ 100 mIU/ml) and strong
response group (HBsAb ≥ 100 mIU/ml) according to children’s HBsAb level at 3 years
old. Logistic regression was used to analyze the influencing factors of immune response to
hepatitis B virus vaccine for 3-year-old children. Results A total of 155 eligible HBV-infected
pregnant women and their delivered infants were included. A total of 39 cases did not take antiviral
drugs during pregnancy and 116 cases took antiviral drugs (lamivudine: 30 cases; tibivudine:
86 cases). In the middle of pregnancy (before treatment), HBV DNA load of pregnant women
in treatment group was (7.35 ± 0.57) lg IU/ml, which was (7.26 ± 0.71）lg IU/ml in untreated
group, the difference was not statistically significant (t = -0.856, P = 0.393). There was
statistical difference in HBV DNA load before delivery between pregnant women in treatment
group and untreated group [(3.69 ± 0.88) lg IU/ml vs (6.77 ± 1.22) lg IU/ml; t = 17.04, P ＜ 0.001].
Total of 23 infants (reseed group) were vaccinated again with hepatitis B virus vaccine between
7 months and 3 years old after birth, the median value of HBsAb of children at 3 years old was
208.84 mIU/ml. There were 132 cases who were not vaccinated again with hepatitis B virus
vaccine, the median value of HBsAb of children at 3 years old was 94.07 mIU/ml, which was
significantly lower than that at 1 year old (370.66 mIU/ml, z = -0.607, P ＜ 0.001). HBsAb
titer of children at 3 years reseed group was significantly higher than that in unreseed group (z =
-2.402, P = 0.016). The rates of no/weak response to hepatitis B virus vaccine of children in
unreseed group were 25.75% (34/132) at the age of 1 year and 51.52% (68/132) at the age of
3 years, respectively, which was 21.74% (5/23) at the age of 3 years in reseed group. None of
the 155 children with successful mother-to-child blockade was infected with HBV at the age
of 3 years old. Multivariate Logistic regression analysis showed that hepatitis B virus vaccine
supplementation was an independent protective factor for the effect of immune response in
3-year-old children (OR = 0.259, 95%CI: 0.09～0.741, P = 0.012). Conclusions Treatment
with antiviral drug during pregnancy could reduce HBV load significantly and not affect the
immune response of infants to hepatitis B virus vaccine. Hepatitis B virus vaccine reseeding
was an independent protective factor of hepatitis B immune response in 3 years old children.
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