Figure 2.

Schematic mechanisms involved in the progression of NAFLD to NASH. Lifestyle factors such as obesity and genetic predispositions contributing to the development of insulin resistance and hepatic steatosis. In the following steps multiple parallel metabolic hits lead to cellular damage, via a process called “lipotoxicity.” Injured hepatocytes initiate an inflammatory response, predominantly via toll-like receptors, and activate proinflammatory signaling pathways in the setting of increased adipokine levels. Also the apoptosis and senescence are alternative cell fates that are likely to be of greater importance to disease progression. Direct recruitment of Kupffer cells and other components of the innate immune response such as dendritic cells occurs with activation of the inflammasome and the coordinated release of proinflammatory and profibrogenic cytokines and ligands. Hepatic stellate cells (HSCs) are subsequently activated to produce extracellular matrix leading to progressive fibrosis and cirrhosis and its complications such as hepatocellular carcinoma (HCC).