title: Mother-to-child transmission of hepatitis B virus: evolution of hepatocellular carcinoma-related viral mutations in the post-immunization era.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Epidemiology, Second Military Medical University, 800 Xiangyin Rd., Shanghai, China.
authors: Zixiong
authors: Z
authors: Li
authors: Center for Disease Control and Prevention of Pudong New District, Shanghai, China.
authors: Zhenyu
authors: Z
authors: Xie
authors: Department of Epidemiology, Second Military Medical University, 800 Xiangyin Rd., Shanghai, China; Department of Virus Research, Center for Disease Control and Prevention of Ningbo, Ningbo, China.
authors: Hongxia
authors: H
authors: Ni
authors: Department of Epidemiology, Second Military Medical University, 800 Xiangyin Rd., Shanghai, China.
authors: Qi
authors: Q
authors: Zhang
authors: Department of Epidemiology, Second Military Medical University, 800 Xiangyin Rd., Shanghai, China.
authors: Wei
authors: W
authors: Lu
authors: Department of Epidemiology, Second Military Medical University, 800 Xiangyin Rd., Shanghai, China.
authors: Jianhua
authors: J
authors: Yin
authors: Department of Epidemiology, Second Military Medical University, 800 Xiangyin Rd., Shanghai, China.
authors: Wenbin
authors: W
authors: Liu
authors: Department of Epidemiology, Second Military Medical University, 800 Xiangyin Rd., Shanghai, China.
authors: Yibo
authors: Y
authors: Ding
authors: Department of Obstetrics and Gynecology, The Central Hospital of Baoshan District, Shanghai, China.
authors: Yan
authors: Y
authors: Zhao
authors: Department of Pediatrics, The Central Hospital of Baoshan District, Shanghai, China.
authors: Yibing
authors: Y
authors: Zhu
authors: Department of Epidemiology, Second Military Medical University, 800 Xiangyin Rd., Shanghai, China.
authors: Rui
authors: R
authors: Pu
authors: Department of Epidemiology, Second Military Medical University, 800 Xiangyin Rd., Shanghai, China.
authors: Hongwei
authors: H
authors: Zhang
authors: Department of Virus Research, Center for Disease Control and Prevention of Ningbo, Ningbo, China.
authors: Hongjun
authors: H
authors: Dong
authors: Center for Disease Control and Prevention of Pudong New District, Shanghai, China.
authors: Yifei
authors: Y
authors: Fu
authors: Center for Disease Control and Prevention of Pudong New District, Shanghai, China.
authors: Qiao
authors: Q
authors: Sun
authors: Department of Virus Research, Center for Disease Control and Prevention of Ningbo, Ningbo, China.
authors: Guozhang
authors: G
authors: Xu
authors: Department of Epidemiology, Second Military Medical University, 800 Xiangyin Rd., Shanghai, China. Electronic address: gcao@smmu.edu.cn.
authors: Guangwen
authors: G
authors: Cao
mesh_terms: D000293:Adolescent; D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D019143:Evolution, Molecular; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications / Q000635:transmission* / Q000821:virology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D017354:Point Mutation; D011247:Pregnancy; D055815:Young Adult
keywords: Evolution; Hepatitis B virus; Hepatocellular carcinoma; Immunization; Mother-to-child transmission; Mutation