高载量慢性乙型肝炎病毒感染孕妇晚孕期应用替比夫定的临床观察

Clinical Observation of Effects of Telbivudine on Pregnant Women at Third Trimester With High Viral Load of Hepatitis B Virus

目的：观察高载量慢性乙型肝炎病毒（HBV）感染孕妇晚孕期应用替比夫定（LdT）抗病毒治疗的疗效、安全性及其阻断母婴垂直传播的作用。方法选取2012年3月至2013年2月于江苏省常州市第三人民医院妇产科门诊进行产前检查的60例慢性 HBV感染孕妇为研究对象,并按照不同用药方式,将其分为LdT组（n=30）和对照组（n=30）（本研究遵循的程序符合江苏省常州市第三人民医院人体试验委员会所制定的伦理学标准,得到该委员会批准,分组征得受试对象本人的知情同意,并与之签署临床研究知情同意书）。两组患者年龄、体质量、孕龄等一般资料比较,差异无统计学意义（P＞0.05）。LdT组孕妇自孕龄为28~32孕周开始口服LdT（600 mg/d）,对照组孕妇未接受抗HBV感染治疗。检测两组孕妇孕龄为28~32孕周前及分娩时血清 HBV DNA载量,LdT组服药期间肝、肾功能水平,新生儿娩出时脐静脉血 HBV DNA载量,所生婴儿月龄为7个月时血清 HBV表面抗原（HBsAg）情况。观察 LdT组孕妇的药物不良反应。结果①两组孕妇孕龄为28~32孕周前血清 HBV DNA载量比较[（1.12±1.46）×108拷贝/mL vs.（9.01±6.65）×108拷贝/mL],差异无统计学意义（t=0.73,P=0.24）；②LdT 组孕妇分娩时（治疗后）HBV DNA载量下降均＞102拷贝/mL,其抗病毒治疗有效率达100%,且两组分娩时 HBV DNA载量＜5.6×103拷贝/mL孕妇数比较,差异有统计学意义（χ2=12.00,P＜0.01）；③LdT 组出现丙氨转氨酶（ALT）轻度升高孕妇为7例（23.3%）,无一例孕妇出现肾功能异常,治疗期均未出现药物不良反应。④LdT组脐静脉 HBV DNA载量＜5.6×103拷贝/mL 新生儿为30例（100%）,对照组为26例（86.6%）,两组比较,差异有统计学意义（χ2=4.29,P＜0.05）。⑤LdT组月龄为7个月婴儿血清 HBsAg 均呈阴性（100%）,对照组呈阴性婴儿为28例（93.3%）,两组比较,差异无统计学意义（χ2=0.52,P＞0.05）。结论 HBV高病毒载量孕妇晚孕期应用 LdT抗病毒治疗可显著降低分娩时血清 HBV DNA载量水平,可有效阻断 HBV垂直传播。

Objective To observe the efficacy and safety of telbivudine（LdT）on pregnancy women with high viral load of hepatitis B virus （HBV）infection during the third trimester.Methods From March 2012 to February 2013,a total of 60 pregnant women with chronic HBV infection were enrolled in this study.They were divided into LdT group （n=30）and control group （n=30）according to whether taking LdT or not.LdT group were administered 600 mg/d LdT from 28-32 gestational weeks and control group were treated without antiviral drugs.Adverse reactions were observed in LdT group after treatment.The serum HBV DNA levels were tested in both groups.The HBV DNA levels of umbilical vein after delivery and serum HBsAg of the baby after seven months were also detected.The study protocol was approved by the Ethical Review Board of Investigation in Human Being of The Third People′s Hospital of Changzhou. Informed consent was obtained from each participants.Results ①There was no significant difference of HBV DNA levels between two groups at 28-32 gestational weeks [（1.12 ± 1.46）× 108 copies/mL vs. （9.01±6.65）× 108 copies/mL]（t=0.73,P=0.24）.②HBV DNA level of LdT group declined over 100 copies/mL when delivering,the anti-viral treatment effective rate in LdT group was 100%.There had significant difference in rates of HBV DNA 〈5.6×103 copies/mL between both groups at childbirth＆amp;nbsp;（χ2=12.00,P〈0.01）.③No seriously adverse reaction and birth defect was found in LdT group.④The rates of HBV DNA〈5.6×103copies/mL of umbilical vein in LdT group was higher than that of control group（χ2=4.29,P=0.05）.⑤After 7 months,babies with HBsAg-positive were found in control group, none in LdT group.Conclusions The usage of LdT on pregnant women with high viral load of HBV during the third trimester can significantly inhibit maternal serum HBV DNA levels,and effectively block HBV vertical transmission with good security.