替诺福韦与安慰剂预防乙型肝炎围产期传播的比较
作者:G.Jourdain,N.Ngo?Giang?Huong,L.Harrison,L.Decker
来源:Thenewenglandjournalofmedicine
背景:PregnantwomenwithanelevatedviralloadofhepatitisBvirus(HBV)haveariskoftransmittinginfectiontotheirinfants,despitetheinfants‘receivinghepatitisBimmuneglobulin.
尽管婴儿接受了乙肝免疫球蛋白注射，乙肝病*（HBV）载量升高的孕妇仍有向婴儿传播HBV的风险。方法:Inthismulticenter,double-blindclinicaltrialperformedinThailand,werandomlyas-signedhepatitisBeantigen(HBeAg)–positivepregnantwomenwithanalanineamino-transferaselevelof60IUorlessperlitertoreceivetenofovirdisoproxilfumarate(TDF)orplacebofrom28weeksofgestationto2monthspostpartum.InfantsreceivedhepatitisBimmuneglobulinatbirthandhepatitisBvaccineatbirthandat1,2,4,and6months.TheprimaryendpointwasahepatitisBsurfaceantigen(HBsAg)–positivestatusintheinfant,confirmedbytheHBVDNAlevelat6monthsofage.Wecalcu-latedthatasampleofwomenwouldprovidethetrialwith90%powertodetectadifferenceofatleast9percentagepointsinthetransmissionrate(expectedrate,3%intheTDFgroupvs.12%intheplacebogroup)在泰国的一个多中心双盲临床试验中，我们将谷丙转氨酶≤60IU/L的乙肝e抗原阳性孕妇随机分配到两组，分别从妊娠28周到产后2个月接受替诺福韦酯(TDF)或安慰剂治疗。婴儿在出生时接受乙肝免疫球蛋白注射，并在出生时和1、2、4、6个月时接种乙肝疫苗。主要终点是婴儿乙肝表面抗原阳性并且在6个月大时由HBVDNA水平证实。我们推测：一个名孕妇的样本量可以检测出两组的传播率至少存在9％的差异(预期的传播率是，TDF组为3%，安慰剂组为12%)，检验效能约为90%。结果:FromJanuarytoAugust,weenrolledwomen;womenwererandomlyassignedtotheTDFgroupandtotheplacebogroup.Atenrollment,themediangestationalagewas28.3weeks,andthemedianHBVDNAlevelwas8.0log10IUpermilliliter.Amongdeliveries(97%oftheparticipants),thereweresingletonbirths,twotwinpairs,andonestillborninfant.ThemediantimefrombirthtoadministrationofhepatitisBimmuneglobulinwas1.3hours,andthemediantimefrombirthtoad-ministrationofhepatitisBvaccinewas1.2hours.Intheprimaryanalysis,noneoftheinfants(0%;95%confidenceinterval[CI],0to2)intheTDFgroupwereinfected,as