Background: Perinatal 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.
Objective: We aimed to elucidate dynamic changes of the HCC-related mutations from maternal perinatal transmission to chronic infection in childhood.
Study design: A 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.
Results: Univariate regression analysis indicated that maternal HBeAg positivity, viral load ≥10(6)copies/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.
Conclusion: Maternally 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.
Keywords: Evolution; Hepatitis B virus; Hepatocellular carcinoma; Immunization; Mother-to-child transmission; Mutation.
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