Figure 7.

Schematic depiction of the role of Kupffer cells (KCs) and hepatic stellate cells (HSCs) in promoting alcohol-induced inflammatory changes and progression to fibrosis and cirrhosis. Injury begins with alcohol-induced hepatocyte damage and death (apoptosis), which generates apoptotic bodies that stimulate KCs to secrete inflammatory factors, such as tumor necrosis factor alpha (TNFα), interferon gamma (IFN-γ), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and Fas ligand (FasL). These factors attract immune cells (e.g., natural killer [NK] cells and natural killer T cells [NKT cells]) to the liver to exacerbate the inflammatory process. Activated HSCs secrete abundant extracellular matrix proteins (e.g., collagen type 1), forming scar tissue (fibrosis) that can progress to cirrhosis. In this condition, the scar tissue forms bands throughout the liver, destroying the liver’s internal structure and impairing the liver’s ability to regenerate itself and to function.