Zixiong Li1, Zhenyu Xie2, Hongxia Ni3, Qi Zhang1, Wei Lu1, Jianhua Yin1, Wenbin Liu1, Yibo Ding1, Yan Zhao4, Yibing Zhu5, Rui Pu1, Hongwei Zhang1, Hongjun Dong6, Yifei Fu2, Qiao Sun2, Guozhang Xu6, Guangwen Cao7. 1. Department of Epidemiology, Second Military Medical University, 800 Xiangyin Rd., Shanghai, China. 2. Center for Disease Control and Prevention of Pudong New District, Shanghai, China. 3. 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. 4. Department of Obstetrics and Gynecology, The Central Hospital of Baoshan District, Shanghai, China. 5. Department of Pediatrics, The Central Hospital of Baoshan District, Shanghai, China. 6. Department of Virus Research, Center for Disease Control and Prevention of Ningbo, Ningbo, China. 7. Department of Epidemiology, Second Military Medical University, 800 Xiangyin Rd., Shanghai, China. Electronic address: gcao@smmu.edu.cn.
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. 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.
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.
Authors: Anna L McNaughton; Peter A Revill; Margaret Littlejohn; Philippa C Matthews; M Azim Ansari Journal: J Gen Virol Date: 2020-03 Impact factor: 3.891