The clinical significance of surface antigen variants of hepatitis B virus

Summary. Hepatitis B surface antigen (HBsAg) is not only critical to the biology of hepatitis B virus (HBV), it is also the basis of the currently available vaccines, assays to detect it in serum are crucial for diagnosis of infection and antibodies against it are used clinically to suppress infection of transplanted livers. All of these rely on antigenic interactions between HBsAg and HBsAb. Thus, it should not be a surprise that changes in epitopes will affect all these situations. It is useful to classify such changes simplistically as variants, found in natural isolates, and mutants, which are observed to emerge, usually under immunological pressure, often medical in origin. The former tend to affect the sensitivity of diagnostic assays and the latter allow escape of viruses in vaccinees and those being treated with HBsAb. The majority of these changes cluster in the hydrophilic central core of HBsAg, from aa99 up to 169. They are gaining importance as causes of mistaken diagnosis and are associated with infection of vaccinees and transplanted livers. There is a danger that they will become the dominant strains as vaccination becomes universal. More data are required on the epidemiology and antigenicity of these changes.