Pathogenesis of Nonalcoholic Steatohepatitis: Interactions between Liver Parenchymal and Nonparenchymal Cells

Figure 1

Schematic illustration of NASH pathogenesis. Multiple hits lead to hepatocyte damage involving excessive oxidative stress driven by lipotoxic metabolites. Injured hepatocytes release damage-associated molecular pattern molecules (DAMPs) that initiate an inflammatory response leading to direct recruitment of neutrophils, macrophages, and other components of the innate immune response. Macrophages and damaged hepatocytes, especially ballooned hepatocytes, instigate the release of profibrogenic cytokines and ligands, such as hedgehog and osteopontin. Hepatic stellate cells (HSCs) are subsequently activated and produce excessive extracellular matrix leading to progressive fibrosis. In addition, macrophages promote a proinflammatory microenvironment that initiates an adaptive immune response, likely mediated by T and B lymphocytes.