The observation that inheritance of the PNPLA3 p.I48M variant, the main genetic determinant of progressive NAFLD, through action on hepatic fat, lipotoxicity, and hepatic stellate cells – fibrogenesis,34 was independently associated with higher F8/PC levels is consistent with the hypothesis that liver damage plays a causal role in determining the procoagulant status typical of individuals with insulin resistance. The gene discussed is PNPLA3; the disease is metabolic dysfunction-associated steatotic liver disease.