Figure 2

Formal pathogenesis of liver fibrosis (fibrogenesis). The "canonical principle" of fibrogenesis starts with necrosis or apoptosis of hepatocytes and inflammation-connected activation of hepatic stellate cells (HSC triggering), their transdifferentiation to myofibroblasts with enhanced expression and secretion of extracellular matrix and matrix deposition (fibrosis). The latter is a precondition for cirrhosis. New pathogenetic mechanisms concern the influx of bone marrow-derived cells (fibrocytes) and of circulating monocytes and their TGF-β driven differentiation to fibroblasts in the damaged liver tissue. A further new mechanism is epithelial-mesenchymal transition (EMT) of bile duct epithelial cells and potentially of hepatocytes. All three complementary mechanisms enlarge the pool of matrix-synthesizing (myo-)fibroblasts in the damaged liver. The most important fibrogenic mediators are transforming growth factor (TGF)-β, platelet-derived growth factor (PDGF), insulin-like growth factor 1 (IGF-1), endothelin-1 (ET-1), and reactive oxygen species (ROS including hydroxyl radicals, superoxid anions). Abbreviations: ASH – alcoholic steatohepatitis; NAFLD – non-alcoholic fatty liver disease. Inset shows an electron micrograph of HSC with numerous lipid droplets indenting the nucleus.