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

Authors Tzilves D., Patsanas Th., Rapti E., Kokozidis G., Kitis G..


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
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