Virus load and liver damage, as measured by quantitative polymerase chain reaction and histology activity index, were related to genotype and core promoter mutations in 43 chronic hepatitis B virus (HBV) carriers of East Asian origin. T-1762 mutants were more frequent in genotype C strains and were associated with more inflammation (P = .0036) and fibrosis (P = .0088) of the liver but not with hepatitis B e antigen (HBeAg) status or virus load. Conversely, precore mutations were associated with less liver inflammation (P =.08), which was linked to HBeAg negativity and lower viral replication. Carriers with genotype C were more often HBeAg positive (P = .03) with precore wild type strains and more-severe liver inflammation (P = .009) than were those with genotype B. These findings suggest that pathogenic differences between genotypes may exist and that the T-1762 mutation may be useful as a marker for progressive liver damage but seem to contradict that down-regulation of HBeAg production is the major effect of this mutation.