Platelet thromboxane B2 overproduction associated with liver fibrosis severity in patients with MASLD

Background and aims: Experimental study demonstrated that platelet cyclooxygenase-1 (COX-1) activation is implicated in the pathogenesis of metabolic dysfunction-associated steatosis liver disease (MASLD). However, the relationship between COX-1 activation and MASLD severity is still unclear. This study aimed to investigate platelet COX-1 activation in patients with MASLD. Methods: This is a cross-sectional study involving patients with biopsy-proven MASLD. Serum Thromboxane B-2 (TxB(2)) levels was measured as a biomarker of ex vivo COX-1 activation potential and plasma sP-selectin as in vivo marker of platelet activation. Oxidative stress biomarkers included serum NOX2-derived peptide (sNOX2-dp) and hydrogen peroxide breakdown activity (HBA). Results: TxB(2) serum levels increased progressively from MASLD simple steatosis (MASLD-SS) to steatohepatitis (MASH) (p = 0.017) and cirrhosis (p = 0.012). Serum TxB(2) (rS = 0.467, p < 0.001) and sNOX2-dp (rS = 0.476, p < 0.001) levels were positively correlated with fibrosis stage and inversely correlated with HBA (rS = -0.506, p < 0.001). In addition, serum TxB(2) correlated with sP-selectin (rS = 0.428, p < 0.001). Multivariate linear regression analysis revealed that TxB(2) associated with liver fibrosis stage (p = 0.007) and sNOX2-dp (p = 0.018). Conclusions: This study provides evidence of platelet TxB(2) overproduction, which increases progressively from MASLD-SS to MASH and cirrhosis and is significantly associated with the degree of liver fibrosis. These findings support the hypothesis that platelet COX-1 activation is involved in the pathogenesis of MASLD.