Mutations that prevent the expression of the hepatitis B e antigen frequent
ly emerge in the immunoreactive phase of infection. The predominant mutatio
n, the precore G-->A-1896 mutation, is restricted by the variability at pos
ition 1858 and is rare in strains with cytosine at nucleotide 1858. The C-1
858 variant is characteristic of genotype A. It also occurs in genotypes C
and F, but not in B, D, or E, explaining the geographical variation in the
prevalence of precore mutants. C-1858 strains have been frequently observed
in southeast Asia, but have not been phylogenetically characterized. By se
quencing eight complete hepatitis B virus genomes, C-1858 variants of east
Asian origin were found to constitute a phylogenetic entity within genotype
C that probably diverged several hundred years ago. Further study of the d
istribution of this variant is warranted.