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


METHODS
This was a prospective, phase I/II, open label, study.


METHODS
The liver intensive therapy unit at King's College Hospital, London.


METHODS
Sequential patients admitted with acute liver failure due to acetaminophen overdose.


METHODS
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.


METHODS
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.
Rolando
N
N
Institute of Liver Studies, Guy's King's & St Thomas' Medical School, London, UK. nancy.rolando@btinternet.com
Clapperton
M
M
Wade
J
J
Wendon
J
J
D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D007958:Leukocyte Count; D017114:Liver Failure, Acute / Q000175:diagnosis / Q000188:drug therapy*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects*; D011446:Prospective Studies; D012016:Reference Values; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D016179:Granulocyte Colony-Stimulating Factor