Thus, our integrated analyses of human NAFLD cases, including pathological scoring, biochemical data and gene expression data, and detailed comparisons with healthy controls enabled us to show that alterations in IRS-2, PEPCK and G6Pase expressions are concurrently induced in the early stage of NAFLD, when histological steatosis and lobular inflammation, but not ballooning and fibrosis, manifest. This evidence concerns the gene IRS2 and metabolic dysfunction-associated steatotic liver disease.