Figure 1

Pathogenetic concepts in hepatic fibrogenesis. Hepatic fibrogenesis is a complex reaction that is triggered by many different noxa, including viruses, alcohol and drugs. At the cellular level, liver residential cells (hepatic stellate cells (HSCs) and portal fibroblasts) and infiltrating profibrogenic cells (PCs; circulating fibrocytes and marrow-derived stem cells) cause the formation of excess production and deposition of extracellular matrix (ECM) components. The pool of fibrogenic cells is further increased by epithelial-to-mesenchymal transition (EMT), in which nonparenchymal epithelial cells transition into mesenchymal cells, and further by mesothelial-to-mesenchymal transition (MMT), in which mesothelial cells from the organ surface migrate into the inner part of the liver and acquire a mesenchymal phenotype. In the fibrotic liver tissue, the turnover of the ECM is changed, several biomarkers are released, physical features (stiffness) are altered and clinical symptoms that are characteristic of liver insult develop. MFB, myofibroblast; MMP, matrix metalloproteinase; TIMP, tissue inhibitor of metalloproteinase.