Hepatocyte-derived sEVs also promoted hepatic fibrosis in NAFLD by directly modulating HSC phenotype and up-regulating the expression of profibrogenic genes, including Col1α1, α-smooth muscle actin (αSMA), and tissue inhibitor of metalloproteinase-2 (TIMP-2) (76). This evidence concerns the gene ACTA1 and metabolic dysfunction-associated steatotic liver disease.