| Objectives Comparing the effectiveness and safety of antiviral drugs to interrupt motherto-child transmission(MTCT)of HBV in high viral load(HBV DNA≥2×105IU/m L)and HBe Ag positive pregnant women with chronic hepatitis B,and determining the best time for the application of antiviral drugs provide scientific basis for the optimization of the MTCT interruption program.Methods Studies referring to high viral load and HBe Ag positive pregnant women with chronic hepatitis B treated with lamivudine(LAM),telbivudine(TBV)or tenofovir(TDF)to interrupt the HBV MTCT were searched from base-building to December 1,2019 in Pub Med,Web of Science,the Cochrane Library,EMBASE,CNKI and Sinomed.The Cochrane and NOS scales were used to evaluate the quality of literatures.In order to evaluate the effectiveness and safety of three antiviral drugs,Stata 11.0 and Ge MTC 14.3softwares were used to realize traditional meta-analysis and network meta-analysis based on Bayesian network model repectively.The selected drugs of possessing better effectiveness and safety were further verified through observational comparative clinical study.Pregnant women with chronic hepatitis B who were treated at two hospitals of Shijiazhuang from January 2017 to May 2019 were screened according to the inclusion and exclusion criterias and grouped according to their medication.The effectiveness and safety of the antiviral drugs to interrupt HBV MTCT were compared between the drugs and the different pregnancy periods.Results 1 meta-analysis.(1)A total of 1521 articles were retrieved,and 35 articles were finally brought into study,including 6109 pregnant women.Among the 35 articles,there were 9 randomized controlled trials,23 cohort studies and 3 retrospective studies.(2)Effectiveness.According to traditional meta-analysis,the positive rates of serum HBs Ag and HBV DNA of infants in the LAM,TBV and TDF groups at birth and 6~12 months after birth,and the HBV DNA levels of pregnant women at delivery were significantly lower than those in the control group(P<0.05).The HBe Ag seroconversion rate had no statistical difference in each group(P>0.05).The ALT returning to normal rates in the three group were higher than the control group(P<0.05).According to network meta-analysis,the serum HBs Ag and HBV DNA positive rates of infants at the 6~12 months after birth in the LAM,TBV and TDF group were significantly lower than those of the control group(95% CI upper limit <1),but there were no statistical differences among the three drugs.The possible rankings of the three drugs in reducing the positive rate of serum HBs Ag and HBV DNA in infants at 6~12 months after birth were LAM<TBV<TDF and LAM<TDF<TBV,respectively.(3)Safety.Based on traditional meta-analysis,there was no statistical difference in the rates of cesarean section and postpartum hemorrhage of pregnant women among the three groups(P>0.05).The creatine kinase(CK)rates of the three group were higher than the control group(P<0.05).There was no statistical difference in the birth weight,birth length and Apar score of the newborns in each group(P>0.05).2Comparative study of clinical effects.(1)A total of 644 pregnant women were brought into study,including 214 cases in the TDF group,380 cases in the TBV group and 50 cases in the control group.(2)Effectiveness.Serum HBV DNA levels of the pregnant women during delivery in the TDF group and TBV group were significantly lower than those in the control group(P<0.05),but there was no statistical difference between the two antiviral treatment groups(P>0.05).The HBe Ag seroconversion rates of the pregnant women and the HBV positive rates of the newborns had no statistical difference among the three groups(P>0.05),but the HBe Ag negative conversion rate in the TDF group was significantly higher than that in the TBV group(P<0.05).The HBV MTCT rates in the TBV group and the TDF group were significantly lower than that in the control group(P<0.05),but there was no statistical difference between the two antiviral treatment groups(P>0.05).The serum HBV DNA level at delivery of pregnant women who started taking TDF in the second trimester was significantly lower than that in the third trimester group(P<0.05),but there was no difference in the TBV group(P>0.05).(3)Safety.The CK increase rate,cesarean section rate,incidence of symptoms and discomfort,and postpartum hemorrhage rate in pregnant women were not different among the three groups(P>0.05).The rates of low birth weight,premature birth and intrauterine distress in newborns among the three groups did not show statistical differences(P>0.05).No serious adverse events occurred in pregnant women or infants of the three groups.There was no significant difference in safety indicators between the second trimester and the third trimester both in TDF group and in TBV group(P>0.05).Conclusions 1 The high viral load and HBe Ag positive pregnant women with chronic hepatitis B receiving LAM,TBV or TDF during pregnancy can effectively reduce the serum HBV DNA level of pregnant women at delivery and interrupt HBV MTCT.2LAM is likely the least effective drug in reducing the positive rate of HBs Ag or HBV DNA in infants at 6~12 months.3 The effects of TBV and TDF in interrupting HBV MTCT are about the same.4 The application of TDF in the second trimester can more effectively reduce the serum HBV DNA level during delivery,but there is no difference in the TBV.5 Taking LAM,TBV or TDF in the second or third trimester of pregnancy is very safe,there is no any serious adverse event both in pregnant women and infants.Figure 20;Table17;Reference 112... |
