title: Severity of the compensatory anti-inflammatory response determined by monocyte HLA-DR expression may assist outcome prediction in cirrhosis.
abstract: OBJECTIVE
  To investigate variations in expression of the monocyte antigen presentation molecule HLA-DR in cirrhosis.
  
  
  METHODS
  HLA-DR expression was measured by flow cytometry in 100 patients within 48 h of admission and repeated a week later in 21 patients admitted to ICU. IL-10, TNF-α and IFN-γ secretion in response to lipopolysaccharide and recall antigens were measured by enzyme-linked immunosorbent spot (ELISPOT) assay in 12 patients (7 with clinical immunoparesis, 5 stable).
  
  
  RESULTS
  HLA-DR level was 71% in stable patients, 53% with single organ dysfunction and 34% with multiple organ failure (p < 0.02). Within these groups, no significant differences in admission HLA-DR were seen between survivors and non-survivors. HLA-DR expression less than 40% predicted 90-day mortality with a specificity of 80% and sensitivity of 59% [area under the receiver operator curve (AUROC) 0.76]. HLA-DR less than 40% was an independent predictor of prognosis in multivariate analysis with a relative risk of 2.35 (p = 0.04), although sequential organ failure assessment score (SOFA) score displaced HLA-DR when included. In those admitted to intensive care failure to increase HLA-DR expression was predictive of death within 30 days (risk ratio 6.9, p = 0.007). Follow-up values predicted outcome with similar accuracy to acute physiology and chronic health evaluation II (APACHE II)/SOFA scores (AUROC 0.88). Response to endotoxin and recall antigen was characterised by an anti-inflammatory cytokine secretion profile, and was associated with impairment in recall antigen presentation capacity.
  
  
  CONCLUSIONS
  HLA-DR expression less than 40% and a failure of recovery predict poor outcome in decompensated cirrhosis, but overall prognostic power remains inferior to conventional markers. Ex vivo experiments demonstrate reduced Th1 response to antigenic stimulation and an exaggerated counter-inflammatory cytokine secretion profile.
authors.affiliation: Institute of Liver Studies, Kings College London School of Medicine, Kings College Hospital, Denmark Hill, London, UK. philaberry@hotmail.com
authors.forename: Philip A
authors.initials: PA
authors.lastname: Berry
authors.forename: Charalambos G
authors.initials: CG
authors.lastname: Antoniades
authors.forename: Ivana
authors.initials: I
authors.lastname: Carey
authors.forename: Mark J W
authors.initials: MJ
authors.lastname: McPhail
authors.forename: Munther J
authors.initials: MJ
authors.lastname: Hussain
authors.forename: Edward T
authors.initials: ET
authors.lastname: Davies
authors.forename: Julia A
authors.initials: JA
authors.lastname: Wendon
authors.forename: Diego
authors.initials: D
authors.lastname: Vergani
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015331:Cohort Studies; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D007362:Intensive Care Units; D008103:Liver Cirrhosis / Q000276:immunology* / Q000503:physiopathology; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D017063:Outcome Assessment, Health Care / Q000379:methods*; D011379:Prognosis; D012720:Severity of Illness Index; D016019:Survival Analysis; D018746:Systemic Inflammatory Response Syndrome / Q000503:physiopathology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006684:HLA-DR Antigens