Biomarkers of Macrophage Activation and Immune Danger Signals Predict Clinical Outcomes in Alcoholic Hepatitis

Autor: Craig J. McClain, Mack C. Mitchell, Patrick Lowe, David Tornai, Svetlana Radaeva, Adeyinka Charles Adejumo, Bruce A. Barton, Arthur J. McCullough, Aimee R. Kroll-Desrosiers, Karen Kodys, Banishree Saha, Gyongyi Szabo, Srinivasan Dasarathy
Rok vydání: 2019
Předmět:
0301 basic medicine
Kaplan-Meier Estimate
Severity of Illness Index
Gastroenterology
Liver disease
0302 clinical medicine
Liver Function Tests
Cause of Death
Osteopontin
Academic Medical Centers
Membrane Glycoproteins
biology
Middle Aged
Prognosis
Disease Progression
030211 gastroenterology & hepatology
Acute Alcoholic Hepatitis
Lipopolysaccharide binding protein
Adult
medicine.medical_specialty
Alcoholic hepatitis
Enzyme-Linked Immunosorbent Assay
HMGB1
Risk Assessment
Article
03 medical and health sciences
Immune system
Antigens
CD
Predictive Value of Tests
Internal medicine
medicine
Humans
Aged
Proportional Hazards Models
Hepatology
Cluster of differentiation
Hepatitis
Alcoholic
business.industry
Macrophage Activation
medicine.disease
Survival Analysis
United States
030104 developmental biology
ROC Curve
Case-Control Studies
Multivariate Analysis
biology.protein
Carrier Proteins
business
Biomarkers
Acute-Phase Proteins
Zdroj: Hepatology
ISSN: 1527-3350
0270-9139
DOI: 10.1002/hep.30617
Popis: Although mortality due to acute alcoholic hepatitis (AH) correlates with Model for End-Stage Liver Disease (MELD) scores, biomarkers are critically needed to manage this disease. Increases in inflammatory markers and macrophage activation are associated with acute AH and could be potential biomarkers of clinical events and/or mortality. We enrolled 89 clinically diagnosed AH patients in four US academic medical centers. Plasma from AH patients had a significant increase in gut microbial translocation indicators (endotoxin, bacterial 16S ribosomal DNA) and host response indicators (soluble cluster of differentiation 14 [sCD14] and lipopolysaccharide binding protein [LBP]) compared to controls. Patient MELD score and Glasgow Alcoholic Hepatitis score (GAHS) correlated with endotoxin levels. AH patients also had a significant increase in high mobility group protein 1 (HMGB1), a sterile danger signal molecule, and osteopontin (OPN), a multifunctional phosphoprotein involved in neutrophil activation, compared to controls. Increased levels of OPN positively correlated with increasing MELD score, GAHS, and LBP levels. Consistent with these results, AH patients had significantly increased circulating levels of macrophage activation (sCD163 and sCD206) markers compared to healthy controls, and sCD163 and sCD206 significantly and positively correlated with OPN, HMGB1, and LBP levels as well as with MELD score and GAHS. These findings indicate a connection between microbial translocation, immune cell activation, and AH severity. Plasma sCD14, OPN, sCD163, and sCD206 levels were significantly higher in nonsurvivors than survivors. In multivariate regression models, we identified sCD14, sCD163, and OPN as independent predictors of 90-day mortality, infection, and organ failure development, respectively. Conclusion: Our study suggests that sCD14, LBP, OPN, sCD163, and sCD206 are biomarkers to indicate severity and predict clinical outcomes in AH.
Databáze: OpenAIRE
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