替比夫定阻断HBV DNA高载量孕妇母婴传播的疗效和安全性观察

目的评价妊娠早期（12周）应用替比夫定阻断高病毒载量孕妇母婴传播的疗效和安全性。方法选择妊娠12周慢性乙型肝炎孕妇80例,病毒载量均超过1×10^7拷贝/ml。按患者意愿分治疗组（替比夫定组）38例和对照组42例,治疗组口服替比夫定600 mg,1次/d,加用复方甘草酸苷保肝治疗,替比夫定服用至产后12周;对照组不给予抗病毒药物,只给予复方甘草酸苷保肝治疗。两组新生儿出生后均接种乙型肝炎免疫球蛋白200 IU与乙型肝炎疫苗20μg。婴儿7月龄时HBsAg及HBV DNA阳性者为HBV宫内感染。观察两组患者母体HBV DNA水平的变化情况和新生儿HBsAg的阳性率。对两组HBsAg阳性率的差异分析采用卡方检验;组间比较行t（t＇）检验,治疗前后的比较采用配对t检验。结果至分娩前,替比夫定组孕妇HBV DNA、ALT水平明显下降。替比夫定组HBV DNA载量于治疗2周后迅速下降,之后缓慢下降直至分娩。替比夫定组服药至分娩前及分娩后12周HBVDNA水平明显降低（t=29.15、40.06,P〈0.01）,而对照组无明显变化（P〉0.05）。替比夫定组分娩前及分娩后12周HBV DNA水平较对照组明显下降（P〈0.01）。替比夫定组新生儿7月龄时HBV感染率为0,明显低于对照组14.3%,差异有统计学意义（χ2=3.99,P〈0.05）,替比夫定组母婴均无不良事件发生,对照组有2例发生严重肝功能异常。两组孕产妇的剖宫产率、不良妊娠率、产后出血率及新生儿的胎龄、体质量、身长、Apgar评分等,差异均无统计学意义。结论乙型肝炎病毒高载量孕妇孕12周开始应用替比夫定可显著抑制孕妇外周血清HBV DNA水平,降低新生儿HBV感染率,并具有良好的耐受性及安全性。

Efficacy and safety of telbivudine in preventing mother-to-infant transmission of HBV in pregnant women with high HBV DNA load

Objective To evaluate the efficacy and safety of telbivudine given from the 12th week of gestation in preventing mother-to-infant transmission of hepatitis B virus（HBV） in pregnant women with high HBV DNA load.Methods Eighty pregnant women（at 12 weeks of gestation） with chronic hepatitis B,who had a HBV DNA load higher than 1.0×107 copies/ml,were enrolled.The patients were divided into two groups according to their personal preferences： treatment group（n=38） and control group（n=42）.The treatment group received oral telbivudine（600 mg） once daily until 12 weeks after delivery and was administered compound glycyrrhizin for liver protection,while the control group was given compound glycyrrhizin for liver protection alone.All infants in both groups were vaccinated with hepatitis B immunoglobulin（200 IU） and HBV vaccine（20 μg） after birth.The mother-to-infant transmission of HBV was indicated by the presence of HBsAg and HBV DNA in infants at 7 months after birth.The HBV DNA levels in these women were measured,and the positive rate of HBsAg in infants was determined.The difference in positive rate of HBsAg was analyzed by chi-square test;the between-group comparison was analyzed by group t（t′）-test,and the before-after comparison was analyzed by paired t-test.Results The treatment group showed significantly decreased HBV DNA and alanine aminotransferase levels before delivery.The HBV DNA load of treatment group dropped rapidly after 2 weeks of treatment and then decreased slowly until delivery.The treatment group had significantly decreased HBV DNA levels before delivery and at 12 weeks after delivery（t=29.15,P0.01;t=40.06,P0.01）,but the control group showed no significant changes（P0.05）.The treatment group had significantly lower HBV DNA levels than the control group before delivery and at 12 weeks after delivery（P0.01）.No infants in the treatment group were HBV-positive,versus a positive rate of 14.3% in the control group（χ2=3.99,P0.05）.No adverse events occurred in the mothers or their infants in treatment group,but two cases of severe hepatic dysfunction were found in the control group.There were no significant differences between the two groups in terms of cesarean section rate,adverse pregnancy rate,and postpartum hemorrhage rate as well as the gestational age,body weight and height,and Apgar scores of neonates.Conclusion Telbivudine given from the 12th week of gestation can significantly decrease the serum HBV DNA level in peripheral blood among pregnant women with high HBV DNA load and reduce the infection rate of HBV in neonates,and it has high tolerability and safety.