Table 1.

Pathways contributing to the development of hepatocellular carcinoma (HCC) from non-alcoholic steatohepatitis (NASH).

Pathway	Primary Mechanism
Cellular	Steatosis followed by lipid peroxidation
Genetic	Elevated PNPLA3 protein levels facilitate lipogenesis Decreased TM6SF2 levels reduce lipid efflux, increase lipid droplet number and size
Immunologic	Cytokine release recruit Kupfer cells and contribute to NASH Decreased NK cells associated with infiltration of monocyte-derived macrophages
Metabolic	Insulin and IGF-1 signaling associated with PI3K and MAPK activation of Wnt/β-catenin along with epigenetic modifications facilitate fibrosis
Endocrine	Androgens stimulate transcription of cell cycle-related kinase (CCRK) which upregulate β-catenin