Dynamics of hepatitis B virus quasispecies heterogeneity in association with nucleos(t)ide analogue treatment determined by MALDI-TOF MS

Minor drug-resistant variants may preexist in every subject infected with hepatitis B virus (HBV). However, understanding the dynamic of genotypic evolution within the HBV population requires accurately following allele frequencies through time. We used MALDI-TOF MS (matrix-assisted laser desorption-ionization time-of-flight mass spectrometry) for localization and quantitative allele frequency detection to investigate preexisting HBV quasispecies and the genotypic evolution of drug-resistant variants during nucleos(t)ide analogue therapy. We found a significant difference between the genotypic evolution of drug-resistant variants depending on response to treatment.