Hepatic Fibrogenesis

Hepatic fibrosis, that is, extracellular matrix deposition and scarring of the liver, is the common pathogenic mechanism of advanced chronic liver diseases, including viral hepatitis, alcoholism, cholestasis, and nonalcoholic fatty liver disease. Progressive fibrosis results in liver cirrhosis and is associated with mortality. Fibrogenesis involves a complex interplay between signals from injured hepatocytes, responses in nonparenchymal cells (e.g., endothelial cells, Kupffer cells), activation and infiltration of immune cells, and, ultimately, the excessive production of matrix proteins from myofibroblasts. Hepatic stellate cells are the major source of myofibroblasts in hepatic fibrosis. An in-depth molecular and cellular understanding of fibrogenesis opens the avenue for novel antifibrotic therapies, regarding which several approaches are currently being tested in clinical trials.