Clinical Application Of Telbivudine And Tenofovir In Blocking Mother-to-child Transmission Of HBV

BackgroundHepatitis B virus(HBV)infection is one of the serious public health problems.In 2016,the HBsAg carrying rate in Chinese population was about 6.1%,and there were about 86 million people with chronic HBV infection.About 15%-25%of people with chronic HBV infection eventually progress to cirrhosis or primary hepatocellular carcinoma,causing heavy economic burden to patients and society.Mother-to-child transmission is the main cause of chronic HBV infection in China.Although with the popularization of hepatitis B vaccine and immunoglobulin,the prevalence of HBsAg in China has decreased significantly,there are still 10%-15%of newborns infected with HBV through mother-to-child transmission.It is an important measure to block the mother-to-child transmission of HBV by standardizing the management of HBsAg-positive pregnant women and their newborns,especially strengthening the monitoring of pregnant women with high HBV DNA viral load during pregnancy and childbirth,and applying nucleoside(acid)drugs(NAs)to reduce HBV DNA viral load in the middle and late pregnancy.The efficacy and safety of NAs antiviral therapy in pregnant women with HBV infection during pregnancy are still worthy of attention.In this study,we explored the clinical application effect and drug safety of different types of NAs in blocking HBV mother-to-child transmission,so as to provide clinical reference for optimizing the selection of HBV mother-to-child blocking scheme.Objective1.To investigate the clinical application effect of telbivudine and tenofovir in blocking mother-to-child transmission of HBV.2.To compare the efficacy and safety of telbivudine,imported tenofovir dipivoxil(Vired)and domestic tenofovir(Beixin)in blocking mother-to-child transmission of HBV,and to provide clinical reference for blocking mother-to-child transmission of HBV.MethodsThe subjects of this study were pregnant women with positive hepatitis B surface antigen(HBsAg)and HBV DNA>2 × 106 IU/mL who were followed up from January 2018 to December 2020 in the outpatient department of infection in Zhujiang Hospital of Southern Medical University.They were divided into group A,group B1 and group B2 according to NAs selection.Three groups were orally administered with LdT,imported TDF(Vired),domestic TDF(Beixin).Record and collect the general information of three groups of pregnant women,baseline data before taking medicine,HBV serological markers,serum HBV DNA quantification,serum biochemical indexes and liver function indexes at 4 weeks,8 weeks,delivery,6-8 weeks and 1 year after delivery.The infants were followed up.The infants were injected with 100 IU of hepatitis B immunoglobulin within 12 hours of birth,and 10μg recombinant yeast hepatitis B vaccine was injected at different sites.Three doses of hepatitis B vaccine were completed according to the ’ 0,1 and 6 months ’ plan.The venous blood of infants aged 7-12 months was collected to detect two pairs of semi-quantitative HBV to determine whether mother-to-child transmission of HBV occurred.Relevant data were collected through Excel table,and SPSS 25.0 statistical software was used for data analysis.Graphpad Prism 8 was used to plot the statistical analysis results.ResultsIn this study,154 pregnant women with HBsAg positive and HBV DNA>106 IU/mL were continuously followed up,including 51 cases in group A,81 cases in group B1 and 22 cases in group B2.There were no significant differences in age,gestational age,average HBV DNA(1g IU/mL)before medication,average ALT(U/L),average AST(U/L)before medication and other biochemical indexes among the three groups of pregnant women(A,B1 and B2)(P>0.05),indicating comparability.The results were as follows:(1)The average HBV DNA levels of pregnant women in groups A,B1 and B2 at the 4th,8th and delivery weeks of medication showed a continuous downward trend,and the three drugs could effectively reduce the HBV DNA load.At delivery,the average HBV DNA(1g IU/mL)of pregnant women in groups A,B1 and B2 was 3.21 ± 1.06,3.33 ± 1.07 and 3.18± 1.01,respectively,and there was no significant difference among the three groups(P>0.05).At delivery,the HBV DNA virological response rates of pregnant women in groups A,B1 and B2 were 25.5%,19.8%and 18.2%,respectively,and there was no significant difference among the three groups(P>0.05).After discontinuation of delivery,the average HBV DNA of the three groups of pregnant women rebounded rapidly and increased to roughly the same level as the baseline at 6-8 weeks after delivery.(2)There was no significant difference in the changes of the average ALT and AST among the three groups of pregnant women at the 4th,8th and delivery weeks of medication(P>0.05).At 6-8 weeks after delivery,the average ALT and AST of pregnant women in groups A,B1 and B2 were significantly higher than those at other time points,and the difference was statistically significant(P<0.05).At 6-8 weeks after delivery,the abnormal rates of ALT in group A,B1 and B2 were 25.0%,36.2%and 41.7%,respectively,and the abnormal rates of AST in group A,B1 and B2 were 28.6%,21.3%and 16.7%,respectively.There was no significant difference in the abnormal rates of ALT and AST among the three groups(P>0.05).There was no significant difference in the average ALT level and abnormal ALT rate among the three groups at 1 year after delivery(P=0.375).(3)155 infants were followed up,and 85 infants were required to complete the follow-up and detect two pairs of semi-quantitative serum hepatitis B at 7-12 months old.The serum HBsAg was negative,and the incidence of mother-to-child transmission of HBV was 0%.(4)One pregnant woman in each group of B1 and B2 took imported TDF and domestic TDF at the initial stage,showing repeated vomiting,fatigue,anorexia,abdominal distension and other gastrointestinal reactions.No obvious adverse drug reactions were observed in the LdT group,and the drug tolerance was good.During the medication,other biochemical indicators TBiL,DBiL,Alb,CK,Cr,Urea were not significantly abnormal.There were no cases of adverse pregnancy events and birth defects associated with taking antiviral drugs.Conclusion1.The application of LdT,imported TDF and domestic TDF in the middle and late pregnancy can effectively block the mother-to-child transmission of HBV.There is no significant difference in virological response rate among the three,and the drug efficacy is equivalent.2.The HBV DNA load of most patients rebounded after withdrawal at delivery,and increased to roughly the same level as before 6-8 weeks after delivery.3.Patients after withdrawal prone to elevated transaminase,mostly in postpartum 6-8 weeks,domestic TDF ALT increased more obvious,in this period need to closely monitor liver function.4.There was no obvious adverse reaction in the application of LdT,imported TDF and domestic TDF in the middle and late pregnancy,and the safety of the three drugs was good.5.There is no significant difference in antiviral efficacy and safety between domestic TDF and imported TDF in the same drug tenofovir,but domestic TDF has lower price cost and more economy.