应用富马酸替诺福韦酯阻断乙型肝炎母婴传播不同停药时间对产后肝功能的影响

Effect of withdrawal time on postpartum liver function in pregnant women receiving tenofovir disoproxil fumarate therapy for blocking mother to child transmission of hepatitis B

目的比较富马酸替诺福韦酯(TDF)阻断乙型肝炎母婴传播在分娩时和产后12周停药对产后出现丙氨酸转氨酶(ALT)异常的影响。方法采用前瞻性研究方法,选取2016年6月至2018年8月于杭州市第一人民医院就诊的HBsAg及HBeAg均阳性的妊娠妇女共84例,随机分为分娩时停药组(42例)和产后12周停药组(42例),最终完成产后24周随访共66例,分娩时停药组35例,产后12周停药组31例。所有患者均于孕24~28周开始服用TDF治疗,定期监测并比较两组患者的HBV DNA载量变化和ALT异常情况,通过多因素Logistic回归分析产后ALT异常的影响因素,采用SPSS 26.0软件进行统计分析。结果两组患者在产后16周HBV DNA载量与基线值相比,差异无统计学意义(Z=-0.742和-1.891,P值均>0.05)。66例产妇中有21例产后出现ALT异常,其中分娩时停药组9例(25.71%,9/35),产后12周停药组12例(38.71%,12/31),两组差异无统计学意义(χ^(2)=1.280,P>0.05),且ALT异常程度在两组间差异亦无统计学意义(χ^(2)=0.527,P>0.05)。经二分类Logistic回归分析发现,孕期ALT异常与产后出现ALT异常独立相关(OR=13.75,95%CI 1.49~126.85,P<0.05)。结论应用TDF阻断HBV母婴传播产后不同时间停药对产后肝功能无明显影响,孕期ALT异常是产后出现肝功能异常的一项危险因素,这类孕妇产后应谨慎停药并严密监测肝功能。

Objective To investigate the effect of withdrawal time on postpartum liver function in pregnant women receiving tenofovir disoproxil fumarate(TDF)therapy for blocking mother-to-child transmission of HBV.Methods A prospective study was conducted in Hangzhou First People’s Hospital from June 2016 to August 2018.A total of 84 pregnant women with HBsAg and HBeAg positive were enrolled and divided into two groups according to simple randomized grouping method with 42 cases in each group.In group A TDF was withdrawn immediately after delivery and in group B TDF was withdrawn 12 weeks after delivery.Finally,66 patients completed the follow-up for 24 weeks postpartum,35 cases in group A and 31 cases in group B.All patients were administered TDF from week 24-28 of pregnancy.HBV DNA loads and ALT levels were regularly measured and compared.Multivariate logistic regression was used to explore the risk factors of postpartum ALT flare.SPSS 26.0 statistical software was used for statistical processing.Results Compared with the baseline levels,the HBV DNA loads at 16 weeks postpartum had no significant changes in both groups(Z=-0.742 and-1.891,both P>0.05).Postpartum ALT flare was observed in 21 of the 66 patients,9 cases(25.71%,9/35)in group A,and 12 cases(38.71%,12/31)in group B(χ^(2)=1.280,P>0.05);and there was no significant difference in the severity of postpartum ALT flare between the two groups(χ^(2)=0.527,P>0.05).Binary logistic regression analysis showed that increased ALT level during pregnancy was an independent risk factor of postpartum ALT flare(OR=13.75,95%CI 1.49-126.85,P<0.05).Conclusions When TDF was used for preventing mother-to-child HBV transmission,withdrawal at different times after delivery had no effect on postpartum liver function.ALT flare during pregnancy is a risk factor for postpartum ALT flare,so TDF should be discontinued carefully and liver function should be closely monitored postpartum for such patients.