Whole genome deep sequencing analysis of viral quasispecies diversity and evolution in HBeAg seroconverters

Abstract Background & Aims We aimed to investigate how viral quasispecies of the hepatitis B virus (HBV) whole genome evolves and diversifies in response to hepatitis B e antigen (HBeAg) seroconversion and viral control utilizing next-generation sequencing (NGS). Methods Fifty HBeAg-positive chronic hepatitis B patients, including 18 treatment-naive and 32 interferon (IFN)-treated individuals, were recruited. Serial HBV whole genomes in serum were analyzed by NGS to determine sequence characteristics and viral quasispecies. Results HBV quasispecies diversity, measured by nucleotide diversity, was negatively correlated with viral load and hepatitis activity. Spontaneous HBeAg seroconverters exhibited significantly greater viral quasispecies diversity than treatment-naive non-seroconverters from >1 year before seroconversion (0.0112 vs. 0.0060, p 1year after seroconversion (0.0103 vs. 0.0068, p Conclusion Higher HBV quasispecies diversity is associated with spontaneous HBeAg seroconversion and IFN-induce HBeAg seroconversion with low viremia, conferring a favorable clinical outcome.