HSCs can be activated by HBV, HCV, cathepsins B and D, PDGF, TGF-β1, matrix metalloprotease (MMP)-9, JNK and insulin-like growth factor-binding protein 5 (IGFBP-5), and they can infiltrate into the HCC stroma. Here, IGFBP5 is linked to hepatocellular carcinoma.