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Reduced monocyte HLA‐DR expression: A novel biomarker of disease severity and outcome in acetaminophen‐induced acute liver failure
Author(s) -
Antoniades Charalambos Gustav,
Berry Philip A.,
Davies Edward T.,
Hussain Munther,
Bernal William,
Vergani Diego,
Wendon Julia
Publication year - 2006
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21240
Subject(s) - medicine , biomarker , acetaminophen , human leukocyte antigen , monocyte , liver failure , hla dr , liver disease , immunology , gastroenterology , antigen , biology , pharmacology , biochemistry
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)‐α and interferon (IFN)‐γ 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‐α ( 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‐α (r = −0.4, P = .02). HLA‐DR percentage level ≤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. (H EPATOLOGY 2006;44:34–43.)