Prevalence and significance of naturally occurring mutations in the surface and polymerase genes of hepatitis B virus

The prevalence and clinical significance of naturally occurring mutations i n the full-length surface and overlapping polymerase genes of hepatitis B v irus (HBV) were analyzed in 42 patients with chronic hepatitis. Mutations w ere observed in 10 patients (24%) in the a determinant region, which is the neutralizing epitope within the major hydrophilic region of the surface ge ne. A high proportion of these mutations (17/18; 94%) occurred in the first loop, unlike mutations induced by immunization, The presence of serum anti body to hepatitis B surface antigen was significantly associated with these mutations. No other region of the surface gene contained any cluster of mu tations. These results suggest that escape mutations commonly contribute to persistency in the natural course of HBV infection. In contrast, mutations affecting the major catalytic domains of the polymerase gene, which could alter susceptibility to antiviral nucleoside analogues, were not detected a t all.