慢性乙型肝炎患者妊娠早期替比夫定抗病毒的疗效及母婴阻断的临床观察

Clinical observation of telbivudine＇s antiviral efficacy and protection against mother-to-infant transmission of chronic hepatitis B during the first trimester of pregnancy

目的 探讨慢性乙型肝炎妇女妊娠早期使用替比夫定抗病毒的疗效、安全性及母婴阻断有效性. 方法 慢性乙型肝炎妊娠早期妇女84例,HBsAg、HBeAg均阳性、HBV DNA≥107拷贝/ml,血清ALT≥4 ULN,拒绝终止妊娠.分为治疗组43例,在妊娠早期使用替比夫定治疗,600 mg/d;对照组41例,在妊娠期不接受抗病毒治疗.两组婴儿出生后均注射乙型肝炎免疫球蛋白和乙型肝炎疫苗.所生婴儿均采用人工喂养.观察孕期肝、肾功能、心肌酶谱、血常规、尿常规,HBV血清标志物、HBV DNA及不良反应.检测婴儿6个月及12月时HBV DNA、HBsAg及生长发育情况、并发症,并进行Apgar评分.采用SPESS 13.0统计软件进行数据处理和分析,率的比较采用x^2检验或Fisher精确概率检验法. 结果 治疗组有1例在妊娠36周出现rtM204I变异,对照组有1例在妊娠28周发生重型肝炎而加用替比夫定抗病毒治疗.在妊娠12、24周、分娩前的ALT复常率：治疗组分别为62.8％、76.7％和88.1％;对照组分别为29.3％、46.3％和60.0％,P值分别为0.002、0.000和0.004.HBV DNA阴转率治疗组分别为20.9％、37.2％和78.6％;对照组均为0,P值分别为0.006、0.001和0.000.e抗原血清学转换率治疗组分别为2.3％、9.3％和21.4％;对照组均为0,P值分别为1.000、0.116和0、002.婴儿6个月HBsAg阳性率和HBV DNA阳性率治疗组分别为2.4％和0;对照组均为17.5％,P值分别为0.027和0.005.12个月HBsAg阳性率及HBV DNA阳性率治疗组均为0;对照组均为17.5％,P值均为0.005. 结论 妊娠早期开始使用替比夫定有较好的抗病毒疗效,可安全有效地阻断乙型肝炎病毒垂直传播.

Objective To explore the antiviral efficacy,safety and protective ability against mother-to-infant transmission of telbivudine in pregnant patiets with chronic hepatitis B （CHB） during the first trimester.Methods Eightyfour gravid women who were diagnosed with CHB,in their first trimester of pregnancy,and had refused to terminate their pregnancies were enrolled; all study participants were clinically classified as active hepatitis cases with positivity for both hepatitis B surface antigen （HBsAg） and hepatitis B e antigen （HBeAg）,HBV DNA ≥ 107 copies/mL and serum level of alanine aminotarnsferase （ALT） of ≥ 4 ULN.Patients with YMDD mutations were excluded from the study.The study participants were divided into a telbivudine treatment group （n =43; administered in the first trimester of pregnancy） and a control group （n =41,consisting of patients who refused to take antivirals）.All babies bom to the women in both groups of the study received standard immune prevention （anti-hepatitis B immunoglobulin plus hepatitis B vaccine） and artificial feeding.Data recorded for the women during pregnancy included clinical findings for tests of hepatic and renal function,myocardial enzymes,blood and urine clinical parameters,hepatitis B virus makers and HBV DNA,as well as notation of any adverse reactions.The neonaes were evahated for presence of HBV infection,paramers of growth and development,presence of complications,and Apgar score.At 6 and 12 months old,all infants were evaluated for HBV DNA level and HBsAg presence.Results The genetic variant rtM204I was detected in one of the women in the treatment group at 36 weeks of pregnancy.One woman in the control group developed severe hepatitis at 28 weeks of pregnancy and was put on the lelbivudine treatment The treatment group showed greater recovery rates of ALT than the control group at 12 weeks of pregnancy （62.8％ vs.29.3％,P =0.002）,24 weeks ofpregnancy （76.7％ vs.46.3％,P =0.000）,and at ante partum （88.1％ vs.60.0％,P =0.004）.The treatment group also showed greater HBV DNA-negative conversion rates at 12 weeks of pregnanay （20.9％ vs.0,P=0.006）,at 24 weeks of pregnancy （37.2％ vs.0,P =0.001） and at ante partum （78.6％ vs.0,P=0.000）,and greater HBeAg seroconversion rates at 12 weeks of pregnancy （2.3％ vs.0,P=1.000）,at 24 weeks ofpregnancy （9.3％ vs.0,P=0.1 1 6） and at ante partum （2 1.4％ vs.0,=0.002）.The HBsAg-positive rates and HBV DNA-positive rates among the infants born to the mothers in the treatment and control groups,respectively,were 2.4％ vs.17.5％ （P =0.027） at birth,0 vs.17.5％（P=0.005）at 6months old and 0 vs.17.5％ （P=0.005）at 12 months old.The Apgar scores were not significantly different for the children born to the mothers from the two groups,and all the children showed parameters of growth development within normal limits.Conclusion Telbivudine administration in the first trimester had a good antiviral curative effect and effectively blocked mother-to-infant transmission in women with CHB.The treatment was safe,causing no obvious adverse reaction in the gravid women or developnental effects on the infaants.