替诺福韦酯对四川地区妊娠中期高HBV载量慢性乙型肝炎孕妇母婴阻断的疗效

Efficacy of tenofovir disoproxil on blocking mother-to-child transmission of hepatitis B virus with high viral load of women in the middle of pregnancy in Sichuan region

目的探讨替诺福韦酯(TDF)在四川地区感染高载量不同基因型乙型肝炎病毒(HBV)妊娠中期孕妇中阻断HBV母婴传播的疗效。方法选择2016年8月至2019年8月成都市公共卫生临床医疗中心收治的高HBV载量乙型肝炎孕妇共258例,根据患者意愿分为观察组(156例)和对照组(102例),观察组孕妇于妊娠第24周开始口服TDF至分娩当日停药,对照组孕妇不予抗病毒治疗。两组孕妇所生婴儿均接受规范的乙型肝炎免疫接种,对抗病毒治疗后孕妇及婴儿的安全性及母婴阻断效果进行比较。结果258例孕妇中HBV基因B型213例(82.5%),C型45例(17.5%),差异有显著统计学意义(χ^2=14.616、P<0.001)。无B/C混合基因型和其他基因型检出。基因B型与基因C型HBV DNA基线载量差异无统计学意义(t=0.752、P=0.458)。两组患者的新生儿早产发生率(χ^2=0.018、P=0.904)、剖宫产率(χ^2=0.038、P=0.813)和产后24 h出血量(t=0.153、P=0.703)差异均无统计学意义。观察组患者分娩时HBV DNA水平较抗病毒治疗前显著降低(t=19.67、P=0.032),随访至产后7个月,观察组婴儿HBsAg阳性者2例(阳性率为1.28%),HBeAg、HBV DNA均为阴性;对照组婴儿HBsAg阳性者9例(阳性率为8.82%),其中HBeAg阳性者6例(阳性率为5.88%),HBV DNA阳性者6例(阳性率为5.88%)。两组婴儿HBsAg阳性率差异有统计学意义(χ^2=4.956、P=0.038)。观察组HBV基因B型及C型在抗病毒治疗后HBV DNA载量均显著下降,差异无统计学意义(t=1.043、P=0.491)。发生母婴传播的11例患者中,8例为基因B型,3例为基因C型,两种基因型母婴传播发生率差异有统计学意义(χ^2=4.527、P=0.045)。观察组中3例孕妇出现轻微头晕、乏力,1例孕妇出现轻微恶心、食欲下降,不良反应发生率为2.6%(4/156)。治疗期间无血磷和血肌酐异常。两组患者新生儿头围、身长、体质量差异均无统计学意义(P均>0.05)。结论四川地区乙型肝炎孕妇HBV基因型以B型为主,TDF用于高HBV载量的妊娠中期乙型肝炎孕妇安全性好,能有效阻断HBV母婴传播。

Objective To investigate the clinical efficacy of tenofovir disoproxil(TDF)on blocking mother-to-child tranmission of hepatitis B virus(HBV)in middle pregnant women with high HBV load of different genotypes in Sichuan region.Methods Total of 258 pregnant cases of hepatitis B with high HBV load were selected from the Public Health Clinical Center of Chengdu from August 2016 to August 2019,and divided into observation group(156 cases)and control group(102 cases)according to their willingness.The patients in observation group were orally given TDF from 24 gestational weeks until delivery,while patients in control group did not receive antiviral therapy.The infants in both groups were given standardized immunizations to hepatitis B.The safety of pregnant women and infants and the effect of mother-to-child blocking after antiviral therapy were analyzed.Results There were 213 cases(82.5%)of HBV genotype B and 45 cases(17.5%)of HBV genotype C among the 258 pregnant women,with significant difference(χ^2=14.616,P<0.001).No B/C hybrid genotype and other genotype were detected.HBV DNA baseline between genotype B and genotype C were not statistically significant(t=0.752,P=0.458).There were no differences between the two groups on preterm birth rate of patients in newborns(χ^2=0.018,P=0.904),the rate of caesarean section(χ^2=0.038,P=0.813)and the amount of bleeding in 24 hours after birth(t=0.153,P=0.703).HBV DNA levels decreased significantly of patients in observation group during delivery than before antiviral treatment(t=19.678,P=0.032).Follow-up to 7 months after delivery,two infants in observation group were detected HBsAg positive(with the positive rate of 1.28%),while HBeAg and HBV DNA were both negative.Nine infants in the control group were detected HBsAg positive(with the positive rate of 8.82%),among whom,6 cases were detected HBeAg positive(with the positive rate of 5.88%)and 6 cases HBV DNA positive(with the positive rate of 5.88%).The positive rates of HBsAg between two groups of infants were statistically significant(χ^2=4.956,P=0.038).HBV DNA load after antiviral therapy of HBV genotype B and C infected cases in observation group were significantly reduced,with no significant difference(t=1.043,P=0.491).Among the 11 patients with mother-to-child transmission,8 were genotype B and 3 were genotype C,and the difference of mother-to-child transmission between the two genotypes was statistically significant(χ^2=4.527,P=0.045).In observation group,3 pregnant women experienced mild dizziness and fatigue,1 case with mild nausea and decreased appetite,the incidence of adverse reaction was 2.6%(4/156).No serum phosphorus and blood creatinine abnormalities occurred during the treatment.The differences between head circumference,length and body mass of newborns in both groups were not statistically significant(all P>0.05).Conclusions HBV genotype of pregnant women with hepatitis B in Sichuan region was mainly genotype B,and the safty of TDF administrated to middle pregnant women with high HBV load and different genotypes was good,also mother-to-child tranmission of hepatitis B virus could be effectively blocked.