The host immune response may be responsible for selection of envelope and precore/core variants of HBV.

The appearance of replication-competent variants of HBV with mutations in the envelope and precore/core proteins emphasizes that these proteins are the focus of immune selection pressure in the human host. The sequence and speed of application of the multiple selection pressures (humoral and possibly cellular) will determine the virological and clinical outcome. When these variant viruses are passed to a new host, in the absence of the immune selection pressures or modified immune pressures which resulted in their selection, a clinical picture different from that seen in the original host may emerge. Although HBV would seem to be highly evolved, it still seems to have the capacity for further diversity. A number of the reported variations have an obvious clinical relevance, but others do not, and further study is required to elucidate their importance. Whether they represent independently transmissible strains of HBV or are all selected during the course of infection, only to be lost in favor of the original strain on infection of another host, also remains to be determined.