Using High Sensitivity Methods To Assess The Current Program Of Prevention HBV Mother-to-Child Transmission

AimWe propose using highly ultrasensitive method to assess the prevalence of occult HBV infection(OBI)in babies undergone the implementation of current prevention of HBV mother-to-child transmission(PMTCT)program,and to explore,if OBI-associated risk factors and the impact of such on their mother.MethodsThe study was divided into three parts.The first part was the HBV marker analysis in offspring after the implementation of current PMTCT program in China.Second,using nested PCR to detect the existence of the HBV DNA and HBV RNA in peripheral blood,and then to assess the current program of PMTCT in China.Third,HBsAg positive mothers were followed up to 1 year after PMTCT,and the changes in liver function and HBV DNA load were observed.ResultsAccording to the current assessment criteria for the efficacy of program of HBV PMTCT in China,the success rate was 100%in 51 babies born to HBsAg positive mothers.In the present study we enrolled 13 such babies who were adhered to PMTCT program.Nested PCR was performed on these 13 babies and this assay revealed and confirmed the positive rate was(11/13).The rate of OBI in babies whose mother with HBeAg positivity was higher than whose mother with HBeAg negativity,?~2=5.318,P=0.021.The Results of HBV gene detection in umbilical cord blood PBMC cells were consistent with those in maternal peripheral blood PBMC cells,while HBV gene was not detected in umbilical cord blood plasma.Although the serum HBV markers of baby were only anti-HBs positive,there were still 5 in 7 cases that could be detected HBV gene.Anti-HBs was the highest at baby 2mon(month)old,with a positive rate of96.1%.HBeAg positive rate was up to 54%at 2 days after birth,and all turned negative at the age of 12mon old.HBeAb positive rate was up to 50%at 2 days old,and it was still positive at 24mon old in one baby.The positive rate of anti-HBc at birth was up to 100%,then gradually decreased,but jumped to 91.9%at 24mon old.The HBeAg positive rates of baby at 2 days old,2mon old were 22.7%,63.6%,93.3%and 0,36.4%,36.4%,respectively,and it showed a positive correlation with the HBV DNA levels of mother.The HBeAb positive rates of baby at 2 days old,2mon old and 7mon old were 77.3%,45.5%,13.3%,and 65.2%,27.3%,6.7%and36.8%,11.1%,0,respectively,and it showed a negative line relation with the HBV DNA level of mother(all P<0.01).HBeAg positive rates of mother were significant correlation with their baby‘s HBeAg positive rates at 2 days old and 2mon old(85.2%and 33.3%,respectively),which were significantly higher than that of baby born to HBeAg negative mother(7.1%and 0%,P<0.01).Similarly,HBeAg positive rates of mother were negatively correlated with the positive rates of their baby's HBeAb.The HBeAb positive rates of baby born to HBeAg-positive mother at 2 days old,2mon old and 7mon old was 18.5%,3.7%and 0%,respectively,which was significantly lower than that of babies born to HBeAg-negative mothers(100%,100%and 60%),all P<0.01.Abnormal liver function was common at baby 2 days old.The rate of mild abnormal liver function was 47.1%,and obvious abnormal liver function was 35.2%,however,no cases of liver failure occurred,and most time do not required special treatment.The total incidences of elevated liver enzymes and hepatitis flare were 33.3%(17/51)and 27.4%(14/51)in mothers after delivery within 1 year,respectively.They were divided into Telbivudine(LdT)group and non-LdT group according to whether applied LdT.The rate of elevated liver enzymes was 60%(6/10)in LdT group,higher than 26.8%(11/41)in non-LdT group.The rate of hepatitis flare was40%(4/10)in LdT group,higher than 24.4%(10/41)in non-LdT group.Only 10%(1/10)in LdT group had obvious abnormal liver function,and 7.3%(3/41)in non-LdT group.All the hepatitis flare was occurred in 3mon old,all of them showed no obviously increase in TBIL.The rate of HBV DNA rebound in LdT group was60%within 1 year,while that in non-LdT group was only 4.9%(2/41).In the LdT group,the HBV DNA rebound mainly occurred within 3 months after delivery,accounting for 5 in 6,and the incidence of hepatitis flare after stopping LdT at postpartum was up to 4 in 6.We found the incidence of hepatitis flare was 33.3%in HBeAg-positive mothers which significantly higher than that of HBeAg negative,8.3%,?~2=4.694,P=0.032.The incidence of hepatitis flare was 53.3%in HBV DNA>10^6 Cs/mL mothers which was higher than that of HBV DNA<10^6 Cs/mL mothers,8.3%,?~2=12.675,P=0.001.It was showed that hepatitis flare occurred in mothers at postpartum was only depended on log10HBV DNA detected before delivery(?=0.507,t=2.747,P=0.009)according to multiple linear regression analysis.ConclusionsThe incidence of OBI was as high as 11 in these 13 cases of babies who had a success in HBV MTCT according to the current evaluation criteria of HBV PMTCT program.Maternal HBeAg positivity is a risk factor for OBI in babies.Umbilical cord blood PBMC cells may be a pathway for mother-to-child transmission of OBI.It is not completely safe evenif only anti-HBs positive in serum markers of HBV in babies.The titers of HBeAg and HBeAb in babies after birth are mainly affected by the maternal HBV DNA level and HBeAg status.Baby‘s HBeAb and anti-HBc are mainly considered to be from its mother which gradually decreased or disappeared after the"successful"prevention,but the positive rate of anti-HBc may rebound at24mon old.Hepatitis flare and the rebound of HBV DNA level after LdT withdrawal were most occurred within 3 months in mothers after baby delivery,therefore,it is a critical period for monitoring liver function and HBV DNA levels in 3 months after delivery.HBeAg-positive and HBV DNA level>10^6 Cs/mL are risk factors for hepatitis flare.