Mutations of Basal Core Promoter and Precore Regions in Hepatitis B Virus Genotypes B and C

BACKGROUND: Mutations in basal core promoter (BCP) and precore regions of hepatitis B virus (HBV) are associated with course and treatment outcomes of chronic HBV infection. While BCP and precore mutation analysis have been carried out in adult patients between different genotypes, this analysis has rarely been performed for chronically infected children. OBJECTIVES: The aim of this study was to assess the mutation profiles of BCP and precore regions in different HBV genotypes in chronically infected children. PATIENTS AND METHODS: A cohort of 245 children and 92 adults with chronic HBV infection was included in this study. BCP and precore regions were analyzed by PCR amplification and sequenced. RESULTS: Ten nucleotide positions, including nt1679, nt1721, nt1753, nt1757, nt1758, nt1762, nt1764, nt1775, nt1856 and nt1858 in BCP/precore regions of HBV genome, showed obviously higher frequencies of mutation in genotype C subjects than in genotype B subjects among children, while there were only three positions, including nt1679, nt1758 and nt1775 showing higher mutation frequencies in genotype C subjects than in genotype B subjects in adults. Several combined mutations were obviously highly distributed in children with chronic HBV genotype C infection, such as G1721A/A1775G/T1858C triple mutation; a novel combined mutation type, exclusively detected in children with chronic HBV genotype C infection. In addition, G1721A/A1775G/T1858C combined mutation was associated with higher viral load and lower age distribution. CONCLUSIONS: The mutation ratio difference between genotypes B and C in children was higher than that of adults and several combined mutations were exclusively detected in children with chronic HBV genotype C infection associated with higher viral load.