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

Abstract

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