Mother-to-child transmission of hepatitis B virus: Evolution of hepatocellular carcinoma-related viral mutations in the post-immunization era

Abstract

BackgroundPerinatal infection and immunoprophylaxis failure of hepatitis B virus (HBV) and viral mutations contributes greatly to the development of hepatocellular carcinoma (HCC). However, little is known regarding evolution of the HCC-related mutations at early stage of chronic infection. ObjectiveWe aimed to elucidate dynamic changes of the HCC-related mutations from maternal perinatal transmission to chronic infection in childhood. Study designA total of 876 hepatitis B surface antigen (HBsAg)-positive pregnant women and 95 HBsAg-positive mother–child pairs were included in this study. HBV mutant quasispecies were determined using clone sequencing. Mother-to-child transmission was identified by genotyping and phylogenestic analysis. ResultsUnivariate regression analysis indicated that maternal HBeAg positivity, viral load ≥106copies/mL, genotype B2, and male fetus significantly increased the risk of HBV trans-placental transmission. The immunoprophylaxis failure was confirmed in 11 (2.48%) 7-month-old infants. The HCC-risk mutations including A1762T/G1764A were present in the mothers’ and cord blood but mostly absent in the 7-month-old infants’. In the 56 mother–child pairs with 1–15 year-old children acquired the infection from their mothers, the frequencies of HBV mutations including A1762T/G1764A and G1896A in genotype B2 or C2 increased consecutively with increasing age of children. These mutations including A1762T/G1764A in genotype C2 and G1896A in genotype B2 were more frequent in mothers than in children (P<0.001). T1753V, C1653T, and G1899A were infrequent in the mother–child pairs. ConclusionMaternally transmitted HBV without the HCC-risk mutations has advantage of infecting infants after the immunization. The HCC-related mutations are sequentially generated since chronic infection established in children.