fig1

Figure 1. Multiple hits lead to onset and progression of NAFLD/NASH to HCC. Diverse signalling pathways involved in metabolic stress such as FFAs ER-stress, cytokine production (IL-6, IL-17, IL-11 and TGF-β), altered immune response, pro-fibrogenic mediators (hedgehog and NF-κB), gut dysbiosis and endocrine defects drive the development of NAFLD/NASH-associated HCC. NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; HCC: hepatocellular carcinoma; FFAs: free fatty acids; ER: endoplasmic reticulum; IL-6: interleukin-6; IL-17: interleukin-17; IL-11: interleukin-11; TGF-β: transforming growth factor β; SNPs: single nucleotide polymorphisms; miRNA: micro RNA; PI3K: phosphatidylinositol 3-kinases; MAPK: mitogen-activated protein kinase; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B-cells; TNF-α: tumour necrosis factor-alpha; ERK: extracellular receptor kinase; JAK: Janus kinase; STAT: signal transducer and activator of transcription