While the mechanism of NASH-related HCC is not fully understood, but the emerging evidence, suggesting the role of hyperinsulinemia secondary to insulin resistance, leads to increased expression of the insulin-like growth factor-1 (IGF-1), which triggers signaling cascade via insulin receptor substrate-1 (IRS-1) and eventually activate the PI3K and MAPK pathways [35]. Here, IRS1 is linked to hyperinsulinism.