title: Reduced monocyte HLA-DR expression: a novel biomarker of disease severity and outcome in acetaminophen-induced acute liver failure.
abstract: Acute liver failure (ALF) shares striking similarities with septic shock where a decrease in HLA-DR expression on monocytes is associated with disease severity and predicts outcome. We investigated monocyte HLA-DR expression in ALF in relation to inflammatory mediator levels and clinical outcome. Monocyte HLA-DR expression was determined in 50 patients with acetaminophen-induced ALF (AALF) and 20 non-acetaminophen-induced ALF (NAALF). AALF patients were divided into dead/transplanted (AALF-NS, n = 26) and spontaneous survivors (AALF-S, n = 24). Fifty patients with chronic liver disease (CLD) and 50 healthy volunteers served as controls. Monocyte HLA-DR expression was determined by double-color flow-cytometry with monoclonal antibodies detecting HLA-DR and monocyte specific CD14. Serum levels of interleukin (IL) -4, -6, -10, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma were concomitantly measured by ELISA. Compared to healthy volunteers (75%) and CLD (67%) monocyte HLA-DR percentage expression was lower in AALF (15%, P < .001) and NAALF (22 %, P < .001). Compared to AALF-S, AALF-NS had lower monocyte HLA-DR % (11% vs. 36%, P < .001) and higher levels of IL-4, IL-6, IL-10 and TNF-alpha (P < .001). HLA-DR percentage negatively correlated with INR, blood lactate, pH and levels of encephalopathy (r = -0.8 to -0.5, P < .01), IL-10 (r = -0.8, P < .0001), TNF-alpha (r = -0.4, P = .02). HLA-DR percentage level <or=15% has a 96% sensitivity and 100% specificity and 98% accuracy in predicting poor prognosis. In conclusion, the strong relationship of monocyte HLA-DR expression with indices of disease severity, mediators of inflammation and outcome indicates a key role for this molecule as a biomarker of disease severity and prognosis.
authors.affiliation: Institute of Liver Studies, King's College Hospital, London, UK. antoniades@doctors.org.uk
authors.forename: Charalambos Gustav
authors.initials: CG
authors.lastname: Antoniades
authors.forename: Philip A
authors.initials: PA
authors.lastname: Berry
authors.forename: Edward T
authors.initials: ET
authors.lastname: Davies
authors.forename: Munther
authors.initials: M
authors.lastname: Hussain
authors.forename: William
authors.initials: W
authors.lastname: Bernal
authors.forename: Diego
authors.initials: D
authors.lastname: Vergani
authors.forename: Julia
authors.initials: J
authors.lastname: Wendon
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects*; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006801:Humans; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D011379:Prognosis; D012720:Severity of Illness Index
chemical_list: D018712:Analgesics, Non-Narcotic; D015415:Biomarkers; D016207:Cytokines; D006684:HLA-DR Antigens; D000082:Acetaminophen