54例高病毒载量乙型肝炎e抗原阳性孕妇抗病毒短期干预的临床安全性及阻断乙型肝炎病毒母婴传播的效果

Clinical safety of short-term antivirus intervention in 54 pregnant women with high viral load of hepatitis B e antigen and the effect of blocking mother-to-child transmission of hepatitis B virus

目的探讨乙型肝炎e抗原(HBeAg)阳性高病毒载量孕妇孕中期开始给予核苷类药物替比夫定短期干预后乙型肝炎病毒(HBV)母婴传播阻断效果及安全性。方法选择2016年11月至2017年11月大连医科大学附属大连市第六人民医院门诊HBeAg阳性慢性HBV感染孕妇54例,血清HBVDNA≥10^10U/L。孕妇在妊娠第24周开始口服替比夫定600mg,1次/d,至分娩当日停用;新生儿分娩后12h内分别注射乙肝疫苗10μg和乙型肝炎免疫球蛋白100U,出生后1和6个月再分别注射乙肝疫苗10μg。于妊娠第12、24、28、32周和产后1、7个月检测HBVDNA(行对数转换)、肌酸激酶(CK)、丙氨酸氨基转移酶(ALT)和总胆红素(TBIL)。婴儿于出生后28~30周检测乙型肝炎表面抗体(HBsAb)和乙型肝炎表面抗原(HBsAg)情况。结果54例孕妇各时间点CK、ALT和TBIL比较差异无统计学意义(P>0.05)。妊娠第28周、妊娠第32周和产后1个月HBVDNA明显低于妊娠12周(5.7±2.2、5.1±2.3和8.3±1.7比9.5±1.0),差异有统计学意义(P<0.05);产后7个月与妊娠第12周比较差异无统计学意义(P>0.05)。54例婴儿出生后28~30周检查结果显示,血清HBsAb>109U/L,血清HBsAg<30U/L。结论高病毒载量HBeAg阳性慢性HBV感染孕妇孕中期替比夫定短期干预可明显降低HBVDNA至安全线以下,干预期间孕妇未出现明显不良事件,停药后HBVDNA均有不同程度反弹,但婴儿病毒学检查结果证实,孕中期替比夫定短期干预后可实现母婴完全阻断。

Objective To investigate the effects and safety of short-term telbivudine intervention on blocking mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in pregnant women with hepatitis B e antigens (HBeAg) positive during mid-gestation. Methods Fifty-four chronic HBV infection pregnant women with HBeAg positive from November 2016 to November 2017 in Dalian Sixth People′s Hospital Affiliated to Dalian Medical University were selected, and the serum HBV DNA(logarithmic transformation) of pregnant women was ≥10^10 U/L. The pregnant women began oral telbivudine 600 mg at the 24th week of pregnancy, 1 time/d, and stopped at the day of delivery. The neonates were injected 10 μg hepatitis B vaccine and 100 U HBV immunoglobin 12 h after parturition, and they were injected 10 μg hepatitis B vaccine at 1 and 6 months of birth. The HBV DNA, creatine kinase (CK), alanine aminotransferase (ALT) and total bilirubin (TBIL) at 12th, 24th, 28th, 32th week of pregnancy and 1, 7 months after parturition were detected. The hepatitis B surface antibody (HBsAb) and hepatitis B surface antigen (HBsAg) of infants during 28 to 32 weeks of birth were detected. Results There were no statistical differences in CK, ALT and TBIL of 54 pregnant women (P>0.05). The HBV DNA at 28th, 32th week of pregnancy and 1 month after parturition was significantly lower than that at 12th week of pregnancy (5.7 ± 2.2, 5.1 ± 2.3 and 8.3 ± 1.7 vs. 9.5 ± 1.0), and there was statistical difference (P<0.05);there was no statistical difference between 7 months and 12th week of pregnancy after parturition (P>0.05). During 28 to 30 weeks of birth, all the neonates showed serum HBsAb > 109 U/L and HBsAg < 30 U/L. Conclusions Short-term intervention with telbivudine in mid-gestation for pregnant women infected with HBV could significantly reduce the level of serum HBV-DNA to the safety level or below. The adverse effects are not found during the telbivudine intervention period. Of note, after drug withdrawal, the HBV DNA level will rebound variously. The virus related detection conducted on the neonates indicates that short-term telbivudine intervention can realize complete MTCT blocking.