Prevalence and Signi®cance of Naturally Occurring Mutations in the Surface and Polymerase Genes of Hepatitis B Virus

The prevalence and clinical signi®cance of naturally occurring mutations in the full-length surface and overlapping polymerase genes of hepatitis B virus (HBV) were analyzed in 42 patients with chronic hepatitis. Mutations were observed in 10 patients (24%) in the a deter-minant region, which is the neutralizing epitope within the major hydrophilic region of the surface gene. A high proportion of these mutations (17/18; 94%) occurred in the ®rst loop, unlike mutations induced by immunization. The presence of serum antibody to hepatitis B surface antigen was signi®cantly associated with these mutations. No other region of the surface gene contained any cluster of mutations. 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 at all. Several hundred million people throughout the world are chronically infected with hepatitis B virus (HBV), which even-tually leads to life-threatening sequelae such as liver cirrhosis and hepatocellular carcinoma [1]. In general, the coordinatio