Objective: To explore the effect of telbivudine treatment in a prevention program on infants born to HBsAg-positive mothers with non-/hypo-responsiveness to hepatitis B vaccine. Methods: A retrospective cohort study with a total of 321 HBsAg-positive pregnant women and their infants enrolled, was conducted. The mothers were recruited from the Third People' s Hospital of Taiyuan, from July 2011 to January 2013. According to the situation of telbivudine intake in second and third trimesters of pregnancy, the participants were divided into two groups: with telbivudine-treated or as control. The neonates were followed up till the age of 12 months. Maternal, neonatal and infantile HBV-M together with HBV DNA in serum were measured using the electro-chemiluminescence immuno-assay (ECLIA) kits and fluorescence quantitative polymerase chain reaction (FQ-PCR) assay, respectively. Results: The rate of non-/hypo-response was 17.99%. After adjusting the potential confounding factors, the telbivudine treatment on HBsAg-positive mothers in the second and third trimesters of pregnancy seemed as the protective factor for non-/hypo-response to hepatitis B vaccine in infants (aRR=0.119, 95% CI: 0.014-0.974). Levels of IFN-γ and IL-10 in telbivudine-treated group were higher than those in the controls (aRR=8.684, 95%CI: 1.977-38.140; aRR=5.330, 95% CI: 1.278-22.236). When the serum levels of IFN-γ and IL-10 in neonatal peripheral blood were higher than 228.47 pg/ml and 174.05 pg/ml respectively, the infants were less likely to be non-/hypo-responsive to the hepatitis B vaccine (aRR=0.300, 95%CI: 0.105-0.857) (aRR= 0.104, 95% CI: 0.030-0.354). Conclusion: Telbivudine treatment provided for the HBsAg-positive mothers in second and third trimesters of pregnancy were less likely to develop non-/low-responsive to hepatitis B vaccine in infants since IFN-γ and IL-10 might have played a vital role in this process.
目的：检测新生儿外周血干扰素-γ（IFN-γ）和白介素-10 （IL-10）含量，探讨HBsAg阳性母亲妊娠中晚期服用替比夫定对婴儿乙型肝炎（乙肝）疫苗无/弱应答的影响。 方法：采用双向性队列研究方法，选择2011年7月至2013年1月在太原市第三人民医院产科分娩的321对HBsAg阳性孕妇及新生儿，根据HBsAg阳性孕妇妊娠中晚期替比夫定服用情况将其分为服药组和未服药组，对新生儿全程接种乙肝疫苗并随访至12月龄。采用电化学发光法（ECLIA）和荧光定量聚合酶链反应（FQ-PCR）分别检测母亲、新生儿及婴儿外周血HBV血清学标志物与HBV DNA，ELISA检测新生儿外周血IFN-γ、IL-10含量。 结果：乙肝疫苗无／弱应答率为17.99%。非条件logistic回归显示，HBsAg阳性母亲妊娠中晚期服用替比夫定是婴儿乙肝疫苗无／弱应答的保护因素（aRR＝0.119，95%CI：0.014~ 0.974）；以新生儿血清IFN-γ、IL-10含量中位数为界分为高含量组与低含量组，研究发现服药组发生新生儿血清IFN-γ、IL-10高含量的可能性较大（aRR＝ 8.684 ，95%CI：1.977~ 38.140 ；aRR ＝5.330 ，95%CI：1.278~ 22.236），新生儿血清IFN-γ、IL-10高含量组发生乙肝疫苗免疫无／弱应答的可能性较小（aRR＝0.300，95%CI：0.105~ 0.857；aRR＝0.104 ， 95%CI：0.030～0.354）。 结论： HBsAg阳性母亲妊娠中晚期服用替比夫定发生婴儿乙肝疫苗无/弱应答的可能性较小，其可能通过促进新生儿IFN-γ和IL-10分泌来降低婴儿乙肝疫苗无/弱应答发生风险。.
Keywords: Hepatitis B vaccine; Interferon-γ; Interleukin-10; Non-/hypo-response; Telbivudine.