Reduced monocyte HLA-DR expression: a novel biomarker of disease severity and outcome in acetaminophen-induced acute liver failure

Hepatology. 2006 Jul;44(1):34-43. doi: 10.1002/hep.21240.


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.

Publication types

  • Comparative Study

MeSH terms

  • Acetaminophen / adverse effects*
  • Adult
  • Analgesics, Non-Narcotic / adverse effects*
  • Biomarkers / metabolism
  • Cytokines / blood
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • HLA-DR Antigens / biosynthesis*
  • Humans
  • Liver Failure, Acute / chemically induced
  • Liver Failure, Acute / metabolism*
  • Male
  • Middle Aged
  • Monocytes / metabolism*
  • Prognosis
  • Severity of Illness Index


  • Analgesics, Non-Narcotic
  • Biomarkers
  • Cytokines
  • HLA-DR Antigens
  • Acetaminophen