Circulating neutrophil dysfunction in acute liver failure.
Systemic inflammation and susceptibility to developing sepsis is common in acute liver failure (ALF) resulting in tissue damage and organ failure. This study characterized the function of circulating neutrophils in 25 patients with ALF and subacute liver failure (SALF). ALF (n=15)/SALF (n=10) patients were prospectively studied and compared with 11 healthy (HC) and 6 septic controls (SC). Neutrophils were isolated on admission to intensive care and every 3-4 days until death / liver transplantation / recovery. Neutrophil phenotype was determined using fluorochrome-labeled antibodies to CD16 and CD11b and assessed by flow cytometry. Neutrophil phagocytic activity (NPA) was determined using fluorescein isothiocyanate-labeled opsonized Escherichia coli and oxidative burst (OB) was determined by the percentage of neutrophils producing reactive oxygen species (ROS) at rest and after stimulation with opsonized E. coli. Physiological variables, biochemistry, arterial ammonia, microbiology, and outcomes were collected. Plasma pro- and antiinflammatory cytokine profiles were performed by enzyme-linked immunosorbent assay. Neutrophil expression of CD16 which recognizes the FcγRIII region of immunoglobulin G was significantly reduced in the ALF cohort (P<0.001) on day 1 compared to HC. NPA was significantly impaired in the SALF cohort compared to HC (P<0.01). Impaired NPA in the ALF and SALF cohorts on admission predicted nonsurvival without liver transplantation (P=0.01). Spontaneous neutrophil production of ROS was not significantly increased in any of the cohorts. E. coli-stimulated OB was preserved in ALF/SALF cohorts but was significantly impaired in the SC group (P<0.05).


CONCLUSIONS
Circulating neutrophils in ALF/SALF have impaired bacteriocidal function similar to that seen in severe sepsis. Neutrophil function indices are important biomarkers in ALF and may be implicated in the development of organ dysfunction and the increased susceptibility to developing sepsis.
Liver Intensive Care Unit and Transplantation, King's College London School of Medicine at King's College Hospital, London, UK; Institute of Liver Studies and Transplantation, King's College London School of Medicine at King's College Hospital, London, UK.
Nicholas J
NJ
Taylor
Anirudh
A
Nishtala
Godhev K
GK
Manakkat Vijay
R Daniel
RD
Abeles
Georg
G
Auzinger
William
W
Bernal
Yun
Y
Ma
Julia A
JA
Wendon
Debbie L
DL
Shawcross
D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D017114:Liver Failure, Acute / Q000276:immunology* / Q000401:mortality / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D011379:Prognosis; D011446:Prospective Studies; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000276:immunology*; D018805:Sepsis / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D012720:Severity of Illness Index; D055815:Young Adult
D016207:Cytokines; D017382:Reactive Oxygen Species