Natural history and therapy of chronic hepatitis B virus infection

The realization that spontaneous loss of viral replication in chronic hepatitis B virus carriers was associated with remission, by whatever criteria, led directly to the search for agents or combinations of agents capable of abbreviating the duration of viral replication. Of those assessed to date, only alpha-interferons have gained wide acceptance as single-agent therapy. Treatment must be for three months on an alternate-day basis; on this regimen, at least one third of patients will develop clinical and biochemical evidence of an exacerbation of hepatitis followed by rapid clearance from serum of all markers of viral replication, and in some cases, also of hepatitis B surface antigen. A large proportion of carriers remains insensitive to alpha-interferons, however, and studies based on the combination of interferons with other agents that have proved less effective, but with different modes of action, are in progress and appear promising.