Administering granulocyte colony-stimulating factor to acute liver failure patients corrects neutrophil defects

Abstract

OBJECTIVES: Neutrophil function is defective in acute liver failure (ALF) and the in vitro ability of granulocyte colony-stimulating factor (G-CSF) to reverse these defects has been reported. The effects of administering G-CSF to ALF patients are presented in this study. DESIGN: This was a prospective, phase I/II, open label, study. SETTING: The liver intensive therapy unit at King's College Hospital, London. PARTICIPANTS: Sequential patients admitted with acute liver failure due to acetaminophen overdose. INTERVENTIONS: G-CSF was given to four groups (each n = 6) of ALF patients as a daily infusion at 25, 50, 100 or 150 microg/m2. A control group of eight patients did not receive G-CSF. MAIN OUTCOME MEASURES: Neutrophil phagocytosis and killing of Staphylococcus aureus and superoxide release before G-CSF administration and at 24 and 96 h thereafter. RESULTS: Neutrophils from patients receiving 50, 100 or 150 microg/m2 G-CSF, but not from control patients or those receiving 25 microg/m2, showed significantly increased phagocytosis and killing at 96 h. Doses of 50 or 150 microg/m2 G-CSF resulted in increased superoxide production at 96 h. No patients discontinued treatment as a consequence of side effects related to G-CSF administration. CONCLUSIONS: G-CSF administration is a safe and effective means of reversing the neutrophil defects of ALF, and may have a role in the prevention and treatment of infection in these patients. A dose of 50 microg/m2/day is as effective as higher doses and was associated with fewer side effects.