In particular, IR strongly predicts the severity of hepatic fibrosis [162], the main determinant of NAFLD prognosis [164], and advanced fibrosis often occurs in NAFLD patients with T2D, even independently of inflammation and NASH [165,166].Therefore, genetic variants that suppress the activation of insulin signaling may induce fibrosis in NAFLD [167]. This evidence concerns the gene INS and metabolic dysfunction-associated steatotic liver disease.