CAJ | 학술논문

目的：通过观察慢性HBV感染孕妇替比夫定治疗前后血清Th1/Th2型细胞因子水平变化，探讨替比夫定阻断HBV母婴传播的免疫机制。方法对2008年4月至2012年9月收治的HBeAg阳性慢性HBV感染孕妇54例进行回顾分析，根据ALT水平分为免疫活化组（n＝18）和免疫耐受组（n＝36），于妊娠中晚期给予替比夫定600 mg/d，常规检测治疗前、分娩前血清ALT、TBil、HBV DNA水平及HBV标志物变化情况，酶联免疫吸附测定法检测Th1型细胞因子[白细胞介素（IL）2、干扰素（IFN）γ]和Th2型细胞因子（IL-4、IL-6）水平。正态分布的计量资料采用t检验，非正态分布的采用非参数检验。以Bivariate分析两变量相关性，用Pearson相关系数表示相关性。结果替比夫定治疗后血清HBV DNA水平明显下降（P＜0．01），ALT、TBil水平均无显著变化，无HBeAg血清学转换。相较于健康人群，2组在治疗前和分娩前均表现为IL-2（健康人群＜4 pg/ml）和IFNγ（健康人群＜15 pg/ml）高表达，而 IL-4（健康人群＜10 pg/ml）和IL-6（健康人群＜5 pg/ml）低表达。治疗前和分娩前的IL-2、IFNγ、IL-4和IL-6水平在2组之间差异均无统计学意义（P＞0．01）。分娩前较治疗前，免疫活化组IL-4水平有升高（P＝0．014），但均未超出正常上限；IL-2、IFNγ和IL-6水平无显著变化（P＝0．182、0．259、0．710）；免疫耐受组IL-2、IFNγ、IL-4和IL-6水平均无显著变化（P＝0．651、0．839、0．650、0．542）。结论 HBV感染孕妇妊娠中晚期血清Th1型细胞因子高表达、Th2型细胞因子低表达；替比夫定短期治疗对孕妇Th1/Th2平衡影响较小，其参与阻断HBV母婴传播可能通过其他途径发挥作用。
목적：통과관찰만성HBV감염잉부체비부정치료전후혈청Th1/Th2형세포인자수평변화，탐토체비부정조단HBV모영전파적면역궤제。방법대2008년4월지2012년9월수치적HBeAg양성만성HBV감염잉부54례진행회고분석，근거ALT수평분위면역활화조（n＝18）화면역내수조（n＝36），우임신중만기급여체비부정600 mg/d，상규검측치료전、분면전혈청ALT、TBil、HBV DNA수평급HBV표지물변화정황，매련면역흡부측정법검측Th1형세포인자[백세포개소（IL）2、간우소（IFN）γ]화Th2형세포인자（IL-4、IL-6）수평。정태분포적계량자료채용t검험，비정태분포적채용비삼수검험。이Bivariate분석량변량상관성，용Pearson상관계수표시상관성。결과체비부정치료후혈청HBV DNA수평명현하강（P＜0．01），ALT、TBil수평균무현저변화，무HBeAg혈청학전환。상교우건강인군，2조재치료전화분면전균표현위IL-2（건강인군＜4 pg/ml）화IFNγ（건강인군＜15 pg/ml）고표체，이 IL-4（건강인군＜10 pg/ml）화IL-6（건강인군＜5 pg/ml）저표체。치료전화분면전적IL-2、IFNγ、IL-4화IL-6수평재2조지간차이균무통계학의의（P＞0．01）。분면전교치료전，면역활화조IL-4수평유승고（P＝0．014），단균미초출정상상한；IL-2、IFNγ화IL-6수평무현저변화（P＝0．182、0．259、0．710）；면역내수조IL-2、IFNγ、IL-4화IL-6수평균무현저변화（P＝0．651、0．839、0．650、0．542）。결론 HBV감염잉부임신중만기혈청Th1형세포인자고표체、Th2형세포인자저표체；체비부정단기치료대잉부Th1/Th2평형영향교소，기삼여조단HBV모영전파가능통과기타도경발휘작용。
Objective To evaluate the changes in serum levels of Th1/Th2 cytokines in pregnant women with chronic hepatitis B virus (HBV)infection after telbivudine treatment and to investigate the immune mechanism by which telbivudine blocks the mother-to-infant transmission of HBV.Methods Fifty-four HBeAg-positive pregnant women with chronic HBV infection were enrolled from April 2008 to September 2012,and they were divided into two groups based on their alanine aminotransferase (ALT)levels:immune active group (n=18)and immune tolerant group (n=36).Telbivudine was administrated at a dose of 600 mg per day during the second or third trimester. Before treatment and prior to delivery,the serum levels of ALT,total bilirubin (TBil),HBV DNA,and HBV markers were routinely meas-ured,and the levels of Th1 cytokines (interleukin-2 (IL-2),interferon -γ(IFNγ))and Th2 cytokines (interleukin-4 (IL-4),in-terleukin-6 (IL-6))were determined by enzyme-linked immunosorbent assay.SPSS 18.0 was used for statistical analysis.Results After treatment,HBV DNA level was reduced significantly (P<0.01),while there were no significant changes in serum ALT and TBil and no HBeAg seroconversion.Compared with the healthy population,before treatment and prior to delivery,both treatment groups showed high-er expression of IL-2 (healthy control <4 pg/ml)and IFNγ(healthy control <15 pg/ml)but lower expression of IL-4 (healthy control <10 pg/ml)and IL-6 (healthy control<5 pg/ml).Furthermore,there were no significant differences in IL-2,IFNγ,IL-4,and IL-6 levels between the two groups (P>0.01).Prior to delivery,IL-4 level was elevated in immune active group (P=0.014),but within the limits of normal range,while IL-2,IFNγ,and IL-6 levels showed no significant changes (P=0.182,0.259,and 0.710,respective-ly);the levels of IL-2,IFNγ,IL-4,and IL-6 in immune tolerant group showed no significant changes (P=0.651,0.839,0.650, and 0.542,respectively).Conclusion Th1 cytokines are highly expressed while Th2 cytokines are lowly expressed in the second or third trimester among HBV-infected pregnant women.Short-term telbivudine treatment has limited influence on Th1/Th2 balance in HBV-in-fected pregnant women,indicating that other mechanisms might be recruited for interfering with the mother-infant transmission of HBV.