The problem of antiviral therapy for chronic hepadnavirus infections.
Attempts at antiviral therapy of patients with active liver disease as a consequence of chronic hepatitis B virus infection have been moderately successful. The molecular and cellular basis for a successful outcome in these patients is not understood and the same therapies do not appear to benefit carriers that still have fairly normal livers and only a moderate hepatitis as a result of the immune response to the infection. Most carriers fall into this latter classification, at least during the early years of infection, and a therapy that could be successfully applied before extensive liver damage had occurred would presumably reduce the risk of subsequent liver damage and the progression to primary hepatocellular carcinoma. Traditionally, it has been assumed that the primary reason that individuals become chronically infected is that the cytotoxic T-cell response and/or antibody-dependent killing of infected hepatocytes is insufficient to clear the infection. Less attention has been focused on the role of the antibody response in the generation of virus-neutralizing antibodies as the possible major deficiency predisposing some individuals to become carriers. However, carriers normally are antigenemic for HBsAg and virus, and carriers with only antibodies to these structures in their circulation are virtually unknown. In addition, it is usually assumed that the hepatocyte, the major target of infection, does not spontaneously turn over and that, in the absence of an immune response to the infected cell, hepatocellular viability is unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)
Fox Chase Cancer Center, Philadelphia, PA 19111.
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Mason
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D002908:Chronic Disease; D015613:Hepadnaviridae / Q000187:drug effects*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000382:microbiology; D014777:Virus Diseases / Q000188:drug therapy*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents