Severity of the compensatory anti-inflammatory response determined by monocyte HLA-DR expression may assist outcome prediction in cirrhosis

Abstract

To investigate variations in expression of the monocyte antigen presentation molecule HLA-DR in cirrhosis. 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). 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. 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.