Objective:

To summarize the mechanistic involvement of platelets in metabolic dysfunction-associated steatohepatitis (MASH) and evaluate their potential as therapeutic targets, highlighting their significance in disease progression.

Key Findings:

• Platelet activation correlates with MASH severity, inflammation, and fibrosis, suggesting a role in disease progression.
• Activated platelets release inflammatory mediators that contribute to liver injury, indicating a potential therapeutic target.
• MASH patients exhibit a hypercoagulable state with increased thrombin generation and reduced natural anticoagulants, complicating treatment.
• Platelet-derived microparticles and neutrophil extracellular traps amplify coagulation-inflammation crosstalk in the liver, highlighting their role in disease mechanisms.

Interpretation:

Platelets are critical in the pathophysiology of MASH, influencing inflammation, coagulation, and liver injury, suggesting they may be viable therapeutic targets that warrant further investigation.

Limitations:

• Current understanding of platelet-MASH interactions is limited and complex, necessitating more comprehensive studies.
• Heterogeneity of MASH and confounding factors like obesity and insulin resistance complicate the clinical picture, indicating a need for diverse patient studies.
• Robust clinical evidence is needed to confirm the safety and effectiveness of platelet-targeted therapies, particularly in varied populations.

Conclusion:

Future research should focus on clarifying the molecular mechanisms of platelet interactions in MASH to develop personalized treatment strategies, particularly in diverse patient populations.