PILOT-STUDY OF RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN THE TREATMENT OF CHRONIC HEPATITIS-B

Recombinant human granulocyte-macrophage colony-stimulating factor is being used to improve the immunological function of patients with various diseases and to ameliorate hematological disorders. We investigated the tolerance and possible antiviral effect of the administration of daily doses of recombinant human granulocyte-macrophage colony-stimulating factor (3, 1 or 0.5 mug/kg body wt) to nine patients with chronic hepatitis B, alone or in combination with 5 MU interferon-alpha2b. Recombinant human GM-CSF reduced significantly (p < 0.02) hepatitis B virus DNA levels. The three doses used were equally effective. Of the eight patients who completed the study, four became negative for HBV DNA and HBeAg; two of them seroconverted to HBe antibody. These four patients showed improvement in the histological activity of their liver disease. Ultimately, two patients regained normal ALT values. 2',5'-Oligoadenylate synthetase activity increased significantly (p < 0.01) in cell lysates of mononuclear cells cultured in vitro, coinciding with the reductions in hepatitis B virus DNA levels. Recombinant human granulocyte-macrophage colony-stimulating factor was well tolerated but produced a dose-dependent increase in white blood cell counts. It became intolerable at doses of 3 mug (and was reduced to 1.5 mug); this effect was reversible after cessation of recombinant human granulocyte-macrophage colony-stimulating factor treatment. No remarkable variations occurred in other parameters. In conclusion, recombinant human granulocyte-macrophage colony-stimulating factor administration is safe and tolerable at doses of 0.5 to 1 mug/kg body wt and may exert an antiviral effect in chronic hepatitis B. The efficacy of granulocyte-macrophage colony-stimulating factor should be considered in the prevention of hematological disorders and in the increased susceptibility to bacterial infections, during interferon therapy in chronic hepatitis B virus infection.