We thank Maria Bond for technical assistance with manuscript preparation. Additional Supporting Information may be found in the online version of this article. “
“Systemic inflammation and susceptibility to developing sepsis is common in acute liver failure (ALF) resulting in tissue damage and http://www.selleckchem.com/products/ink128.html 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 DNA Damage inhibitor 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. 上海皓元医药股份有限公司 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). Conclusion: 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. (HEPATOLOGY 2013) Acute liver failure (ALF) is a rare but frequently catastrophic consequence of an acute primary hepatic injury arising from a wide variety of insults. It is characterized by coagulopathy and encephalopathy, with a variable dynamic of progression to multiple organ dysfunction syndrome (MODS) and death.1 Liver transplantation (LT) remains the only curative option for advanced ALF with poor prognostic criteria and contributes to ∼10% of LT in the Western world.2 Neutrophils are a major innate immune cell subset involved in the first line of defense against infection.