乙型肝炎病毒表面抗原和e抗原双阳性乙型肝炎病毒高载量孕妇孕晚期应用替比夫定行母婴阻断的疗效

目的评价妊娠晚期对乙型肝炎病毒（HBV）表面抗原（HBsAg）和HBV e抗原（HBeAg）双阳性的高HBV载量孕妇应用替比夫定行HBV感染母婴阻断的疗效。 方法选取2007年7月1日至2017年6月30日于首都医科大学附属北京地坛医院产科门诊进行系统产前检查的慢性HBV感染孕晚期（妊娠28周）孕妇及其分娩婴儿作为研究对象,分析血清HBsAg和HBeAg双阳性、肝功能正常、HBV DNA≥ 1 × 10⁶拷贝/ml,且获得完整随访资料的孕妇共250例,向患者充分告知HBV母婴阻断孕期抗病毒用药的利弊,根据知情自愿原则,按照患者是否服用替比夫定,分成替比夫定组（150例）及对照组（100例）。替比夫定组孕妇自孕28周起口服替比夫定600 mg/d,至分娩后42 d止。对照组孕妇则不应用抗病毒药物。检测两组受试者在孕28周和分娩时血清HBV DNA载量;观察替比夫定组孕妇服药后出现的不良反应。两组孕妇的婴儿出生后均接受主、被动联合免疫;在出生6 h内、1月龄和6月龄时肌内注射乙肝疫苗各10 μg,均于出生后6 h内和1月龄时肌肉注射乙肝免疫球蛋白各200 IU。检测婴儿出生后6 h内（于主、被动免疫前抽股静脉血）和7月龄血清HBsAg阳性率及HBV DNA载量。 结果服药后分娩前替比夫定组孕妇平均HBV DNA载量显著低于对照组,差异有统计学意义（t = 31.07、P < 0.001）。替比夫定组与对照组婴儿出生6 h内血清HBV DNA阳性率（0.00% vs. 17.00%）差异有统计学意义（χ² = 27.36、P < 0.001）;新生儿7月龄时,替比夫定组HBV DNA载量均低于检测下限,对照组婴儿HBV DNA阳性率为10.00%。经Fisher精确检验,对照组婴儿宫内感染率显著高于替比夫定组（12.00% vs. 0.00%）,差异有统计学意义（P < 0.001）。替比夫定组使用随访期间未发现严重不良反应,且该组婴儿未发生出生缺陷。 结论随着分娩前孕妇血清HBV DNA载量升高,HBV宫内感染的危险性增加。肝功能正常、HBsAg及HBeAg双阳性,HBV DNA高载量孕妇孕晚期应用替比夫定抗病毒治疗可显著降低妊娠晚期孕妇血清HBV DNA载量,有效阻断HBV宫内感染,对母婴均具有良好的安全性。

Effect of telbivudine on maternal-infant blocking of hepatitis B virus surface antigen and e antigen in pregnant women with high load of hepatitis B virus in late pregnancy

ObjectiveTo evaluate the efficacy of tebivudine in the treatment for maternal-infant blockade of pregnant women with both serum hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive and high load of hepatitis B virus (HBV) infection in late pregnancy. MethodsFrom July 1st, 2007 to June 30th, 2017, pregnant women with chronic HBV infection in late pregnancy (28 weeks of pregnancy) and babies delivered in the outpatient Department of Gynaecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University were selected. Total of 250 pregnant women with both HBsAg and hepatitis B e antigen (HBeAg) positive, normal liver function, HBV DNA ≥ 1 × 10⁶ copies/ml and with complete follow-up data were collected. The pregnant women were fully informed of the advantages and disadvantages of the maternal-infant blocking of the anti-viral medication during pregnancy. According to the voluntary principle, the pregnant women were divided into tebivudine group (150 cases) and control group (100 cases) according to whether treated with tebivudine. The pregnant women in tebivudine group received oral tebivudine 600 mg/d, from 28 weeks of pregnancy to 42 days after delivery. The control group did not use antiviral drugs. The serum HBV DNA load were detected in both groups at 28 weeks and at the time of delivery. The adverse reactions of pregnant women in tebivudine group after taking medicine were observed. The infants of both groups were immunized with active and passive immunization after birth; hepatitis B vaccine was injected intramuscularly within 6 hours, 1 month and 6 months, respectively, while intramuscular injection of hepatitis B immunoglobulin for 200 IU. The positive rate of HBsAg and the load of HBV DNA in 6 hours after the bith and at 7-month of the baby were detected (venous blood was drawn before passive immunization). ResultsCompared with the control group, the average HBV DNA load was significantly lower in tebivudine group after treatment and before delivery, with significant difference (t = 31.07, P < 0.001). The positive rate of serum HBV DNA in tebivudine group was significantly higher than that of control group within 6 hours of the babies birth, with significant difference (0.00% vs. 17.00%; χ² = 27.36, P < 0.001). At the age of 7 months, the HBV DNA load of the infants in tebivudine group were all lower than the limit of detection, and the positive rate of HBV DNA in the control group was 10.00%. Fisher accurate test showed that the intrauterine infection rate of control group was significantly higher than that of tebivudine group (12.00% vs. 0.00%), with significant difference (P < 0.001). No serious adverse reactions were found during the follow-up period of tebivudine use, and no birth defects were found. ConclusionsWith the increase of serum HBV DNA load in pregnant women before delivery, the risk of HBV intrauterine infection increases. Normal liver function, both HBsAg and HBeAg positive, high HBV DNA load with tebivudine antiviral therapy in late of pregnancy could significantly reduce the serum HBV DNA load of pregnant women and block HBV intrauterine infection of effectively. It is safe for both mothers and infants to use tebivudine in late pregnancy.