Co-administration of granulocyte colony-stimulation factor allows completion of interferon therapy in chronic viral hepatitis with neutropenia

SUMMARY Neutropenia, due either to hypersplenism or to myelotoxicity of interferon (IFN), is a contraindication to start or continue IFN treatment. In a prospective, open study the use of granulocyte colony stimulating factor (G-CSF), a growth factor capable of directly and selectively stimulating proliferation, differentiation and function of neutrophils, has been evaluated in combination with IFN A-2a in patients with chronic viral hepatitis. Inclusion criteria, in addition to those for IFN treatment, were compensated disease (Child-� class A), leukocyte count< 3,0 k/�l and/or neutrophil count < 1,5 k/�l. The dose of G-CSF was titrated in order to raise and maintain the white cell counts above these levels throughout the treatment period and limited to <5�g/Kg subcutaneously daily. Twelve patients (F: 7, M: 5, mean age 45,7, range 23-59), 7 with B and 5 with C infection entered the study. Ten of these, 5 with active cirrhosis and 5 with chronic active hepatitis completed a combined interferon + G-CSF therapy period of 6 months, with a mean total G-CSF dose of 10,5 mg (range 4,8-21.6 mg) per patient. In the other two patients, treatment was stopped at 3 and 4 months because they developed ascites and peripheral oedema due either to loss of compensation or to fluid retention caused by G-CSF. No other important side-effects were observed and, in particular, no excess leucocytosis. At the end of the treatment period, 4 patients showed complete biochemical and virological response to IFN, 4 partial and another 2 no response. These preliminary results suggest that prolonged administration of G-CSF is relatively safe in chronic viral liver disease and allows completion of a course of IFN therapy in neutropenic patients. Key words: G-CSF, Granulocyte colony- stimulating factor, Hepatitis, Therapy, Interferon, Neutropenia