Effects of interferon and adenine arabinoside treatment of hepatitis B virus infection on cellular immune responses.
Fifteen patients with chronic hepatitis B were treated with adenine arabinoside (Ara-A) or human leukocyte interferon (HLI). Cellular immune response to hepatitis B virus surface antigen and antigens prepared from herpes simplex virus, varicella zoster virus, and cytomegalovirus was measured by a lymphocyte blast transformation assay and an assay for interferon production. Measurements were made before, during, and after antiviral treatment. Unlike patients convalescing from acute hepatitis B, only 2 of 15 patients with chronic hepatitis B had significant blast transformation to hepatitis B surface antigen. One such response occurred during the pretreatment period of HLI therapy, and the other was in a patient undergoing low-dose (<10(5) U/kg per day) HLI therapy. Mononuclear cell cultures were tested for interferon production in the presence of hepatitis B surface antigen. Cells from only 1 of 15 patients produced detectable levels of interferon. In contrast, all of these patients had normal cellular immune responses to herpesvirus antigens. Transformation responses to herpes antigens decreased three- to fivefold after patients were treated with >10(5) U of HLI per kg per day. Antiviral therapy with <10(5) U of HLI per kg per day or Ara-A did not produce a detectable depression of transformation response. Ara-A produced marked lymphocytopenia and a marked lymphocyte fragility after 5 or more days of therapy. In vitro Ara-A was toxic to lymphocytes at concentrations as low as 0.5 mug/ml. These changes in lymphocyte parameters may affect the outcome of antiviral therapy.
D000208:Acute Disease; D000328:Adult; D002908:Chronic Disease; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy* / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000032:analysis; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007372:Interferons / Q000627:therapeutic use*; D007958:Leukocyte Count; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D014740:Vidarabine / Q000627:therapeutic use*
D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D007372:Interferons; D014740:Vidarabine