Platelet-mediated progression of fatty liver disease in metabolic dysfunction-associated steatohepatitis: a pathophysiological review

Metabolic dysfunction-associated steatohepatitis (MASH) represents a progressive stage of metabolic dysfunction-associated steatotic liver disease (MASLD), marked by hepatic inflammation, cellular injury, and fibrosis, with potential progression to cirrhosis and hepatocellular carcinoma if not appropriately managed. Increasing evidence highlights that platelets play a significant role in MASH pathogenesis beyond their classical function in hemostasis. Enhanced platelet activation and alterations in platelet indices have been strongly correlated with disease severity, inflammatory activity, fibrotic progression, and unfavorable clinical outcomes. This review summarizes current insights into the mechanistic involvement of platelets in MASH, emphasizing their roles in inflammatory pathways, immune cell interactions, oxidative stress, and dysregulated coagulation, in addition to their interplay with metabolic disturbances. It also evaluates the utility of platelet-related markers as non-invasive indicators for disease progression and clinical monitoring. Moreover, the review explores the therapeutic potential of targeting platelet activity, including the application of antiplatelet agents either alone or in combination with antifibrotic and metabolic therapies. Although these approaches show encouraging potential, robust clinical evidence is still required to establish their safety and effectiveness. Despite recent advances, important gaps persist in understanding the molecular basis of platelet-liver interactions. Future investigations should focus on clarifying these mechanisms to facilitate the development of precise, personalized treatment strategies for MASH.