Hepatitis B virus mutations during mother-to-children transmission: a preliminary study

Abstract

Objective To explore the mutations of hepatocellular carcinoma(HCC)-related hepatitis B virus(HBV)during mother-to-child transmission,so as to provide theoretic evidence for prophylaxis of HCC from the very beginning.Methods A total of 413 HBsAg-positive mothers and their newborns were enrolled in this study.Serum HBV DNA levels in maternal peripheral blood and cord blood of the newborns were measured using real-time quantitative PCR.Nested PCR together with cloning and sequencing methods were applied to examine the HCC-related HBV mutations in the preS and basal core promoter regions of HBV genome.All the newborns received standard HBV vaccination.Of the 413 newborns,104were successfully followed-up 7 months after birth,and the HBV mutations were examined if their circulating HBV DNA was detectable.Results Of the 413 newborns,41(9.9%)had HBV DNA level103 copies/mL in their cord blood.Four(3.8%)of the 104 newborns who were successfully followed up had circulating HBV DNA level103 copies/mL 7months after birth.Compared to mothers without HBV trans-placental transmission,those with HBV trans-placental transmission had no increase in HBV mutations in the basal core promoter region.However,the viral mutations containing T2898G/C,C3000 T,C3116T,T31 C,and T52 Cin the preS region of HBV subgenotype C2 significantly increased the risk of HBV trans-placental transmission(P0.05).The frequencies of the HCC-related mutations in the preS and basal core promoter regions of HBV genome were not significantly different between maternal peripheral blood and the cord blood of the newborns.Importantly,the HCC-related mutations were rarely found in the HBV-positive infants at 7months after birth.Conclusion The HBV mutations in the preS region of HBV subgenotype C2 may affect the trans-placental transmission of HBV.However,the quasispecies of HCC-related HBV mutants have no advantage in causing chronic HBV infection in infants.The HBV mutants which can promote HCC are selected during the long term chronic infection.