Platelet Proteomics: A Glimpse Into Metabolic Dysfunction‐Associated Steatotic Liver Disease Pathogenesis

Aim Metabolic dysfunction–associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease, yet its underlying mechanisms remain incompletely understood. Beyond hemostasis, platelets actively participate in inflammation, fibrosis, and vascular remodeling. This study investigated platelet proteomic alterations across MASLD stages to explore their potential contribution to disease progression. Methods We analyzed 25 MASLD patients undergoing hepatic catheterization and 21 viral‐hepatitis controls. Platelets were isolated from sinusoidal and peripheral blood and profiled using high‐throughput, mass spectrometry–based proteomics. Differential‐abundance and pathway analyses were performed with appropriate statistical correction and exploratory evaluation. Results A total of 1052 platelet proteins were identified. Several proteins showed large effect sizes and are reported as putative markers: histidine‐rich glycoprotein and ADP‐ribosylation factor‐like protein 8B were less abundant in MASLD than in controls. In advanced disease, perforin‐1 and macro‐H2A1 were increased in sinusoidal blood, suggesting immune activation and endothelial injury. Docking protein 1 and TGF‐β–induced protein IG‐H3 were enriched in patients with perisinusoidal fibrosis and obliterative venopathy. Conclusions Putative platelet‐derived proteins associated with immune regulation, vascular remodeling, and metabolic dysfunction were identified in MASLD. These exploratory findings will be validated in a prospective, metabolically matched cohort to confirm disease specificity.