Platelet Functional Profile Is Altered in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Area of Science:

• Hepatology
• Hematology
• Vascular Biology

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) is a primary cause of chronic liver disease, frequently advancing to cirrhosis.
• Platelet activation is implicated in MASLD progression, but its functional characteristics across different fibrosis stages are not well understood.

Purpose of the Study:

• To characterize platelet function and phenotype in patients with MASLD, stratified by fibrosis severity (≤F2 vs. F3-F4), compared to healthy controls.

Main Methods:

• Analysis of in vivo platelet activation biomarkers: urinary 11-dehydro-thromboxane B2 (11-dh-TXB2) and plasma soluble P-selectin.
• Assessment of platelet phenotype using microfluidic assays and flow cytometry, measuring adhesion, fibrinogen receptor activation, and Annexin V binding.
• Stratification of patients based on liver stiffness measurement (LSM) into low fibrosis (MASLD ≤F2) and advanced fibrosis/cirrhosis (MASLD F3-F4) groups.

Main Results:

• Urinary 11-dh-TXB2 levels were elevated in advanced fibrosis (F3-F4) MASLD patients compared to controls.
• MASLD patients with ≤F2 fibrosis showed increased platelet adhesiveness and procoagulant activity.
• MASLD patients with F3-F4 fibrosis exhibited increased adhesiveness but reduced fibrinogen receptor activation, despite elevated activation markers.

Conclusions:

• Platelet activation markers are associated with MASLD fibrosis severity, suggesting a role in disease progression.
• Distinct platelet functional profiles exist between early and advanced MASLD fibrosis.
• Platelets represent potential biomarkers and therapeutic targets for MASLD.