SHH and hepatocellular carcinoma: As one of major secretary ligands for Hedgehog signaling pathway which has been well documented to play a predominant role in HCC initiation, progression, drug resistance and metastasis in our previous studies 34, 35, sonic hedgehog (SHh) ligand is secreted in both paracrine and autocrine fashions; the transcription factor, Gli-1, was identified to increase in progenitor cells in precarcinogenic dysplastic lesions in the transition from NASH-fibrosis to HCC 16.