高HBV载量女性孕中期使用替诺福韦阻断母婴传播的效果及安全性评估

Efficacy and Safety of Tenofovir Disoproxil Fumarate in Pregnant Women with A High HBV Load During the Second Trimester for Prevention of Vertical Transmission of HBV Infection

探讨高HBV(Hepaitis B virus,HBV)载量孕妇妊娠中期使用替诺福韦阻断母婴传播的效果和安全性。以2017年10月1日至2019年12月30日期间在北京地坛医院待产及分娩慢性HBV感染女性及所生婴儿为研究对象,根据母亲HBV载量分为病毒载量低于检测下限组(199例)、低病毒载量组(<2×105 IU/mL但高于检测下限,596例)及高病毒载量组(≥2×105 IU/mL,298例)。按规范化HBV母婴阻断流程高病毒载量组孕24周加用替诺福韦抗病毒,分娩后停药;所有婴儿出生后接受乙肝疫苗及乙肝免疫球蛋白联合免疫预防。收集产妇孕期病毒学指标和临床生化指标、孕期并发症信息及分娩相关信息;婴儿出生后及7月龄时HBsAg、HBV DNA。三组产妇年龄、基线HBV DNA水平及HBeAg阳性率差异有统计学意义(F=15.743,P=0.001;H=892.660,P=0.00;H=632.044,P=0.01);高病毒载量组产妇分娩前血清HBV DNA 4.33(3.48,5.0)IgIU/mL显著低于用药前HBV DNA8.23(7.98,8.23)IgIU/mL,差异有统计学意义(P=0.00);7月龄时高病毒载量组2名(0.67%)婴儿发生HBV感染,低病毒载量组(0%)及病毒载量低于检测下限组(0%)无婴儿感染,三组间阻断失败率差异无统计学意义(P=0.107);高病毒载量组用药后肌酐(CREA)升高(P=0.00)。三组孕妇分娩前ALT、TBIL、肌酐、孕期并发症差异均无统计学意义(P>0.05);三组婴儿先天畸形率、早产率、胎龄、低体重儿比率和Apgar评分差异无统计学意义(P>0.05)。高HBV载量女性于孕中期使用替诺福韦可降低HBV母婴传播且安全性良好。

To evaluate the efficacy and safety of tenofovir disoproxil fumarate(TDF)during the second trimester to reduce hepatitis B virus(HBV)transmission in highly viremic mothers.A total of 1093 eligible mothers and children were enrolled:298 in the high⁃viral⁃load group(mothers’HBV DNA≥2×105 IU/mL),596 in the low⁃viral⁃load group(0<mothers’HBV DNA<2×105 IU/mL)and 199 in a group with HBV DNA that was under the limit of detection(mothers’HBV DNA was not detectable).All infants received standard combination immunoprophylaxis after birth.In the high⁃viral⁃load group,all women received TDF(300 mg,q.d.)during the second trimester.We investigated virological indicators,biochemical results,and complications during pregnancy and childbirth.Serum levels of the surface antigen of the hepatitis B virus(HBsAg)and/or HBV DNA in infants were determined after birth(venous blood was collected before vaccination)and at 7 months of age.There were significant differences in age,baseline HBV DNA level,and prevalence of hepatitis B viral protein(HBeAg)positivity among the three groups(F=15.743,P=0.001;H=892.660,P=0.00;H=632.044,P=0.01).Serum HBV DNA was 4.33(range,3.48–5.0)IgIU/mL before delivery in the high⁃viral⁃load group,which was significantly lower than before delivery(8.23(range,7.98–8.23)IgIU/mL)and the difference was significant(P=0.00).At age 7 months,no chronic HBV infection occurred in children in the low⁃viral⁃load group or HBV DNA was under the limit of detection.Two cases(0.67%)in the high⁃viral⁃load group became infected,but the difference between the three groups was not significant(P=0.107).In the high⁃viral⁃load group,the serum creatinine level increased after TDF was administered(P=0.00).Before delivery,there were no significant differences in levels of alanine aminotransferase,creatinine,or prevalence of pregnancy complications(P>0.05).There were no significant differences in the prevalence of congenital malformations,premature birth,gestational age,low birthweight ratio,or Apgar score among the three groups(P>0.05).The current standardized strategy can reduce the risk of mother⁃to⁃child transmission(MTCT)of the HBV significantly in pregnant women.Antiviral treatment with TDF in pregnant women with a high viral load during the second trimester can reduce MTCT of HBV.