Hepatitis B virus basal core promoter/precore mutants and association with liver cirrhosis in children with chronic hepatitis B virus infection

Clin Microbiol Infect. 2016 Apr;22(4):379.e1-379.e8. doi: 10.1016/j.cmi.2015.10.033. Epub 2015 Nov 11.

Abstract

We investigated 168 children and analysed the virological characterization and association with disease progression in children with hepatitis B virus (HBV) basal core promoter/precore (BCP/PC) mutants. Among 168 patients with HBV infection (aged 0.5-18 years old, mean 10.1), 86 of them had HBV-related liver cirrhosis (LC) and 82 had HBV-related chronic hepatitis B (CHB). A direct sequencing method was employed to determine the HBV genotypes and the mutations in BCP/PC regions. In all, 133 of them were infected with genotype C viruses (79.17%); only 35 patients (20.83%) were infected with genotype B viruses. Both LC patients and CHB patients had significantly higher ratios of genotype C when compared with the ratios of genotype B (83.7%-16.3% versus 74.4%-25.6%). For patients with CHB, the prevalence of BCP/PC wild-type viruses was 52.4%; but this was only 4.7% in patients with LC. The C1653T, T1753C, A1762T/G1764A and G1896A mutations had a significantly higher prevalence in patients with LC. Among all the patients with genotype B viruses, those with LC had lower HBV DNA levels and higher G1899A mutation frequency than patients with CHB. Among all the patients with genotype C viruses, the patients with LC had higher prevalence of C1653T, A1762T/G1764A and G1896A mutation frequency, higher hepatitis B e antigen (HBeAg) -negative rates, lower viral load, lower elevated alanine aminotransferase and lower anti-HBe positive rates than CHB patients. The HBV BCP/PC variants were more common in HBeAg-negative LC patients than in the CHB group (BCP, 53.4% versus 15.6%; PC, 18.6% versus 3.7%, respectively, p < 0.001). Patients with HBV genotype C viruses, high viral load and C1653T, A1762T/G1764A, G1896A mutant viruses, were more susceptible to developing LC.

Keywords: Basal core promoter; genotype; hepatitis B virus; infant; mutation; precore.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • DNA, Viral / genetics
  • Female
  • Genotype
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / isolation & purification
  • Hepatitis B, Chronic / complications*
  • Hepatitis B, Chronic / pathology
  • Hepatitis B, Chronic / virology*
  • Humans
  • Infant
  • Liver Cirrhosis / pathology*
  • Male
  • Mutation Rate
  • Point Mutation*
  • Promoter Regions, Genetic*
  • Sequence Analysis, DNA
  • Viral Core Proteins / genetics*
  • Viral Load

Substances

  • DNA, Viral
  • Viral Core Proteins