替比夫定干预的HBV携带孕妇分娩前后Th1/Th2型细胞因子的动态变化研究

Th1/Th2 Cytokines Level Changes in Telbivudine Treated Pregnant Hepatitis B Virus Carrier before and after Delivery

目的观察孕晚期替比夫定(Ld T)干预的慢性乙型肝炎病毒(HBV携带孕妇分娩前后辅助性T细胞(Th)1和Th2细胞因子的动态变化。方法选择2014年1-12月在首都医科大学附属北京佑安医院产科就诊并分娩的60例HBV携带孕妇为研究对象。所有入组患者于妊娠晚期(26~30周)开始应用Ld T(600 mg/d)抗病毒治疗,产后4~8周停药。分别于Ld T干预前、分娩前及产后4~8周进行3次随访,监测孕产妇的肝功能、HBV DNA水平、HBV血清学、Th1/Th2细胞因子水平的动态变化。结果产后有35例(58.3%)产妇的血清ALT的水平维持在正常水平;25例(41.7%)产妇的血清ALT≥正常值上限(ULN),其中16例(26.7%)血清ALT为(1~2)倍ULN,9例(15.0%)血清ALT≥2倍ULN,1例血清ALT>10倍ULN。分娩前以及产后HBV DNA水平均较干预前水平下降(均P<0.001),产后HBV DNA水平较分娩前升高(P<0.05)。分娩前乙型肝炎表面抗原(HBs Ag)较干预前下降趋势,但差异无统计学意义(P<0.05),而产后HBs Ag水平与干预前以及分娩前比较,差异均无统计学意义(均P>0.05)。产后有19例(31.67%)孕妇乙型肝炎e抗原(HBe Ag)滴度较干预前下降50%以上,其中有3例(5.0%)转阴。产后Th1细胞因子[白细胞介素(IL)-2、肿瘤坏死因子(TNF)-α]和Th2细胞因子(IL-4、IL-6及IL-10)水平均高于干预前和分娩前水平(P<0.05),γ干扰素水平低于干预前和分娩前水平(P<0.05);分娩前Th1细胞因子(IL-2、TNF-α)和Th2细胞因子(IL-4、IL-10)水平与干预前比较差异无统计学意义(P>0.05),分娩前γ干扰素和IL-6水平显著低于干预前(P>0.05)。结论应用Ld T干预的慢性HBV携带孕妇分娩前后Th1和Th2细胞因子发生动态变化,总体上为孕期中低表达,产后高表达,维持动态平衡。

Objective To observe the dynamic changes of Th1/Th2 cytokines levels among peripartum of pregnant women with hepatitis B virus（HBV） infection blocked by telbivudine （LdT）. Methods A total of 60 pregnant women of chronic HBV carders in the obstetrical department of Beijing You＇an Hospital Affiliated to Capital Medical University from Jan. 2014 to Dee. 2014 were enrolled in the study. All the enrolled cases were treated with LdT （600 mg/d） for antiviral therapy from third trimester（26-30 weeks of gestation） to 4-8 weeks postpartum. The women were followed up before the treatment, during perinatal period and 4-8 weeks postpartum respectively. The dynamic changes of hepatic function, serum HBV DNA level,HBV serology and Th1/Th2 cytokines were monitored. Results At postpartum,the alanine aminotransferase（ALT） levels of 35 puerperas（58.3% ） remained normal,25 cases（41.7% ） were more than 1 ×upper litnit of normal（ULN）, among them, 16 cases（26.7% ） were （1-2） × ULN,9 cases（ 15.0% ） were ≥2 × ULN,one case was higher than 10 × ULN. The levels of HBV DNA postpartum and pre-delivery were declined than before intervention （ both P 〈 0. 001 ）, the level of postpartum was higher than pre-delivery （ P 〈 0.05）. The HBsAg level of pre-delivery was lower than before intervention,but there was no significant difference （P 〉 0.05 ） , and postpartum level had no significant difference compared with before intervention and pre-delivery（P 〉0.05）. HBeAg titer of 19 cases（31.67% ） declined 50% postpartum,3 cases （5.0%） turned negative. The serum Thl cytokines （ IL-2, TNF-α） and Th2 cytokines （ IL-4, IL-6 and IL-10） levels postpartum were higher than before intervention and pre-delivery（ P 〈 0.05 ）, the interferon （IFN） -γ level was lower than before intervention and pre-delivery （ P 〈 0.05 ）. There was no significant difference between pre-delivery and before intervention on serum Thl cytokines （ IL-2 ,TNF-α） and Th2 cytokines（ IL-4 and IL-10） （ P 〉 0. 05 ）, the levels of IFN-γ and IL-6 pre-delivery were lower than before intervention （ P 〈 0. 05 ）. Conclusions Using LdT as intervention to the chronicHBV pregnant women before and after childbirth,Th1 and Th2 levels have dynamic changes,mainly presented as low Th1 and Th2 expression during pregnancy and high postpartum expression,malntaining a dynamic balance in general.