Procoagulant imbalance is associated with hepatic and vascular complications in patients with MASLD and diabetes. Key role of factor VIII

Background: Metabolic-dysfunction associated steatotic liver disease (MASLD) promotes fibrosis and vascular complications, especially if associated with type 2 diabetes. Aim: To evaluate the association between procoagulant imbalance, hepatic and vascular damage. Methods: 185 diabetic MASLD patients (62±11ys, 59% males) underwent assessment of of FibroScan® (LSM≥8 kPa), macro- and micro-vascular complications. In 96 patient PNPLA3 genotyping, coagulation factors (i.e., factor (F)VIII, protein C (PC), antithrombin and thrombin generation assay were also assessed. Results: The endogenous-thrombin-potential [ETP (with/without thrombomodulin), called ETP-TM ratio)] and the FVIII/PC ratio increased from tertile 1 to 3 (from 0.65±0.15 to 0.92±0.41, p<0.001), as well as FVIII/PC (from 1.23±0.41 to 1.57±0.77, p=0.003) and were independently associated with increasing LSM values (b-coefficient, 6.11; CI95% 3.59-8.64; b-coefficient, 4.80; CI95% 2.28-7.32). Antithrombin and PC correlated to LSM≥ 8kpa (OR 0.92, CI95% 0.88-0.97; OR 0.97, CI95% 0.94-0.99). When added to the model, PNPLA3 modified some of these associations, but remained independently associated with peak-thrombin ratio (b-coefficient 0.063; CI95% 0.001-0.126) and antithrombin (b-coefficient -6.14; CI95% -11.82 -0.46). FVIII and fibrinogen were independently associated with micro-vascular complications. Conclusion: MASLD diabetic patients display a procoagulant profile, which is independently associated with the severity of hepatic fibrosis and micro-vascular complications. PNPLA3 determine a possible procoagulant profile associated with fibrosis, but further studies are warranted to elucidate this mechanism.