title: The severity of circulating neutrophil dysfunction in patients with cirrhosis is associated with 90-day and 1-year mortality.
abstract: BACKGROUND
  Patients with cirrhosis are susceptible to sepsis, pre-disposing to the development of encephalopathy, bleeding and organ dysfunction with associated high mortality.
  
  
  OBJECTIVE
  To characterise circulating neutrophil function in a cirrhotic cohort as a determinant of 90-day and 1-year mortality.
  
  
  METHODS
  Sixty-two patients with cirrhosis [49 stable (Child-Pugh A/B/C = 24%/39%/37%); 13 acute-on-chronic liver failure] were prospectively studied and compared with 11 healthy controls. Neutrophil function was evaluated at baseline and repeated at critical points during the course of the patient's illness until death/transplantation. Neutrophil phenotype was determined using fluorochrome-labelled antibodies to CD16/CD11b and assessed by flow cytometry. Neutrophil phagocytic activity (NPA) and capacity (NPC) were determined using FITC-labelled opsonised Escherichia coli. Oxidative burst (OB) was quantified by the percentage of neutrophils producing reactive oxygen species (ROS) and mean fluorescence intensity at rest, and after stimulation with E. coli. Physiological variables, biochemistry, microbiology and outcomes were collected. Plasma pro- and anti-inflammatory cytokine profiles were performed by ELISA.
  
  
  RESULTS
  NPA/NPC was impaired in cirrhosis with the most significant dysfunction being observed in those with advanced disease and in those treated with propranolol. NPC predicted survival in stable cirrhosis [AUROC 0.83 (95% CI 0.68-0.97); P = 0.021] and differentiated survivors from nonsurvivors (90-day P = 0.01; 1 year P < 0.001). Resting OB ≥12% predicted 90-day mortality with 80% sensitivity and 71% specificity [AUROC 0.81 (95% CI 0.64-0.97); P = 0.026 and differentiated survivors from nonsurvivors; P = 0.015].
  
  
  CONCLUSIONS
  Circulating neutrophils in patients with cirrhosis are dysfunctional and predict the development of infection, organ dysfunction and survival at 90 days and 1 year.
authors: Liver Intensive Care Unit, 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.
authors: N J
authors: NJ
authors: Taylor
authors: G K
authors: GK
authors: Manakkat Vijay
authors: R D
authors: RD
authors: Abeles
authors: G
authors: G
authors: Auzinger
authors: W
authors: W
authors: Bernal
authors: Y
authors: Y
authors: Ma
authors: J A
authors: JA
authors: Wendon
authors: D L
authors: DL
authors: Shawcross
mesh_terms: D000328:Adult; D016207:Cytokines / Q000276:immunology; D004926:Escherichia coli; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000276:immunology* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis; D011446:Prospective Studies; D017382:Reactive Oxygen Species / Q000276:immunology; D016897:Respiratory Burst
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species