Telbivudine For The Prevention Of Perinatal Transmission Of Pregnant Women With Hepatitis B Virus Infection

BackgroundThe infection of Hepatitis B virus(HBV)has seriously endangered human health,and mother-to-child-transmission(MTCT)is one of the important ways of HBV infection.After the birth of timely injection of hepatitis B immunoglobulin(HBIG)combined with hepatitis B vaccine to block MTCT of HBV more than 90%,but there are still 5%to 10%children is not successful,resulting in HBV vertical infection.The level of HBV-DNA is the most important factor affecting MTCT of HBV,and the higher HBV-DNA(>107copies/mL)mother’s newborns are more likely to have MTCT.In recent years,some studies have shown that the application of antiviral drugs in the mid pregnancy can reduce the serum HBV-DNA level and further improve the success rate of the maternal infant blocking.Telbivudine(LdT)as an effective antiviral drug,blocking the antiviral effect of vertical transmission and safety has been widely concerned.ObjectiveTo evaluate the efficacy and safety of LdT use during mid pregnancy inreducing HBV transmission in highly viremic mothers.MethodsHBeAg+ mothers between weeks 24～28 of gestation with normal liver function and HBV-DNA>1.0×107copies/mL were eligible for enrollment from the Second Hospital of Shandong University between October 2015 and December 2017,as a carrier arm.Women of child-bearing period of chronic hepatitis B(CHB)which conforms to antiviral indications(HBeAg positive,HBV-DNA>1.0×107copies/mL,ALT increased>2xULN)are defined as the CHB arm.Two arms of patients took LdT 600 mg/d.The carrier arm was stopped immediately after delivery and could be breastfed.The CHB arm continued to take LdT.Detection of ALT,serology(HBsAg,HBeAg),HBV-DNA quantitative and CK of two arms were detected baseline,1,3months(ante partum).The carrier arm continued to follow up to 6 months after postpartum.After drug withdrawal,there were temporary no hepatic therapy if ALT were increased to(1～3)xULN.However,the routine drug treatment should be given if ALT was rised larger than 3xULN,and continue to follow up.Data were analyzed using method of statistics to investigate the efficacy and safety of Ldt in the treatment of mother-to-child block.Results1.61 patients enrolled:40 in carrier arm(6 pregnancy)and 21 in CHB arm.In carrier arm,HBV-DNA was(7.99 ± 0.43)lg10copies/mL,ALT was(25±8.25)U/L before treatment,the time of starting LdT was 27(24～28)weeks,and the treatment time was 13(6～15)weeks.In CHB arm,HBV-DNA was(7.65±0.42)lg10copies/mL,ALT was(175.38 + 35.16)U/L before treatment,and the follow-up time was 13(12～13)weeks.All patients were initially treatment.2.The baseline of two arms about HBV-DNA levels was similar.Prior to delivery,maternal HBV-DNA levels were(3.81 ±0.99)lg10copies/mL in carrier arm lower than baseline(P<O.001),CHB arm to(2.76±0.27)lg10copies/mL,decreased viral load was obviously higher than that of the carrier arm(P<0.001).The negative rate of HBV-DNA in CHB arm was 19.05%(4/21),was significantly higher than that of the carrier arm(27.5%,x2=25.81,P<0.001).3.Prior to delivery,the HBsAg and HBeAg titer in carrier arm decreased slowly compared with baseline(P=0.016,P=0.08).However,the HBsAg and HBeAg titer in CHB arm were decreased significantly compared with baseline at 3 months(P=0.006,P<0.001).The negative rate of HBeAg in CHB arm was 9.52%(2/21),lower than carrier arm((0/40,P<0.001).4.40 parturient in carrier arm,LdT was stopped after delivery,of which 5 parturient had increased ALT in 1 months after delivery(12.5%),which were 70,74,75,81 and 97U/L.There was no hepatic therapy and continue to follow up.In the subsequent 6 months of visits,the 5 patients returned to normal ALT.40 patient with HBV-DNA had a rebound to(7.20 + 0.88)Ig10copies/mL(returned to baseline)at 1 month after drug-stop,which HBV-DNA of the 5 ALT abnormal patients was(7.20±0.68)IglOcopies/mL,showed no significant difference in patients with other 35 patients(P=0,99).HBsAg and HBeAg titers were back to the baseline(P>0.05).There was no significant difference between the above indexes and the baseline at 3 and 6 months after drug-stop(P>0.05).5.3 patients in carrier arm with CK increased during treatment,respectively 228,363,308U/L,and 1 grade CK increased cumulative incidence rate was 7.5%(3/40),no 3 level and above grade.There were no significant difference between the two arm with CK increased rate(P=0.681).6.In carrier arm,the preterm birth rate was 5.0%(2/40),and no higher than the normal pregnant women(5%～5%).40 infants,only a low birth weight,and all other infants of normal weight.28 of 40 infants,babies were followed up for more than six months to complete all the test and mother-to-child transmission.Not a baby HBsAg positive,lead to block mother-to-child transmission(PMTCT)100%success rate.Conclusions1.Elbivudine used during mid trimester in HBeAg+ highly viremic mothers can safely reduce perinatal HBV transmission.2.To the arturient with HBV carriers,LdT be stopped after delivery is safety,however need closely follow-up.3.The application of LdT during the short term pregnancy do not cause a significant increase in CK level.LdT was well-tolerated with no safety concerns in the pregnancy.