Clinical significance of hepatitis B virus genotypes, variants, and mutants.

Emerging evidence suggests that hepatitis B virus (HBV) genotypes may influence the rate of spontaneous and interferon-induced hepatitis B e antigen (HBeAg) seroconversion as well as the natural history of liver disease. In contrast, the dinical significance of precore and core promoter variants associated with HBeAg negative liver disease is less certain in light of the many competing host and virologic factors noted in reported studies. HBV surface mutants are primarily associated with prior vaccine or hepatitis B immune globulin exposure and do not appear to have untoward virulence or association with occult HBV infection. Polymerase mutants with reduced drug sensitivity and phenotypic resistance are commonly detected in patients receiving prolonged antiviral therapy and have a variable impact on disease outcomes. The introduction of additional nucleoside/nucleotide analog agents will likely lead to the development of further unique polymerase mutants with varying pathogenicity and cross-resistance to existing drugs.