Objective of the study Our working hypothesis is that platelets activated by gut-derived metabolites dock in the liver of NAFLD patients and amplify the inflammatory state by releasing pro-inflammatory cytokines/chemokines, which in turn recruit and activate leukocytes in the liver sinusoids. Combined stimuli from leukocytes and platelets would then lead to metabolic reprogramming of hepatocytes, progression to NASH and eventually cirrhosis.
To test this hypothesis, the investigators propose 2 objectives. Primary objective: To identify platelet features that correlate with liver disease progression.
Secondary objective: To study the mechanistic relationship between gut dysbiosis, metabolome composition, inflammation, and platelet activation in chronic liver disease.
age>18;
NAFLD patients according to EASL Guidelines 2016.
decompensated cirrhosis, other causes of chronic liver disease (infectious and immune-mediated); malabsorption syndromes (i.e., celiac disease, food allergy, small bowel bacterial overgrowth);
inflammatory bowel disease; previous GI surgery;
immunodeficiencies; neurological handicaps;
use of NSAIDs, antibiotics, probiotics, or anti-secretory drugs within the 2 months preceding enrollment;
A total of 132 individuals (n=33 subjects with NAFLD, n=33 subjects with histologically proven NASH and n=33 subjects with metabolic non-viral cirrhosis and n=33 healthy volunteers (without NAFLD) will be enrolled at the Policlinico Umberto I-Sapienza University of Rome, defined according to the EASL Guidelines 2016.
Cohort
Cross-sectional
Platelets characterization
Other interventionTo identify platelet features that correlate with liver disease progression and to study the mechanistic relationship between gut dysbiosis, metabolome composition, inflammation, and platelet activation in chronic liver disease.
Inflammatory profiling
To compare the systemic inflammatory state of patients at different stages of liver disease, serum samples will be used to quantify the concentration of 13 inflammatory cytokines (pg/ml), including IL-1β, IFN-α2, IFN-γ, TNF-α, MCP-1 (CCL2), IL-6, IL-8 (CXCL8), IL-10, IL-12p70, IL-17A, IL-18, IL-23, and IL-33, by multiplex bead-based flow cytometric assay. Moreover, serum samples will be analysed by standard ELISA for the presence of HMGB1 and calprotectin (MRP8/14), inflammatory biomarkers that are associated with liver disease progression, and for the presence of DNA-myeloperoxidase complexes that are specific markers of neutrophil extracellular traps (NETs).
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Stefania Basili
Lead sponsor
University of Roma La Sapienza
Sponsor institution
University of Rome Tor Vergata
Collaborator
Catholic University of the Sacred Heart
Collaborator
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