Liver fibrosis

Abstract

Liver damage leads to an inflammatory response and to the activation and proliferation of mesenchymal cell populations within the liver which remodel the extracellular matrix as part of an orchestrated wound-healing response. Chronic damage results in a progressive accumulation of scarring proteins (fibrosis) that, with increasing severity, alters tissue structure and function, leading to cirrhosis and liver failure. Efforts to modulate the fibrogenesis process have focused on understanding the biology of the heterogeneous liver fibroblast populations. The fibroblasts are derived from sources within and out with the liver. Fibroblasts expressing alpha-smooth muscle actin (myofibroblasts) may be derived from the transdifferentiation of quiescent hepatic stellate cells. Other fibroblasts emerge from the portal tracts within the liver. At least a proportion of these cells in diseased liver originate from the bone marrow. In addition, fibrogenic fibroblasts may also be generated through liver epithelial (hepatocyte and biliary epithelial cell)-mesenchymal transition. Whatever their origin, it is clear that fibrogenic fibroblast activity is sensitive to (and may be active in) the cytokine and chemokine profiles of liver-resident leucocytes such as macrophages. They may also be a component driving the regeneration of tissue. Understanding the complex intercellular interactions regulating liver fibrogenesis is of increasing importance in view of predicted increases in chronic liver disease and the current paucity of effective therapies.

Confluent hepatic fibrosis in liver cirrhosis: possible relation with middle hepatic venous drainage

“…On the other hand, perivenular and perisinusoidal fibrosis is commonly seen in alcoholic cirrhosis, and cholestasis-induced liver injury shows biliary interface hepatitis including fibroplasia in the portal area [28]. Furthermore, so-call regenerative nodules in cirrhosis that are carved by progressive hepatic fibrous bands [2] are classified as macro-, micro-, and mixed-nodular cirrhosis, and also tends to depend on the etiologies of the cirrhosis [19]. However, as cirrhosis progresses, the characteristic histologic features of various etiologies may be lost, and the features of specific types of cirrhosis may be indistinguishable from cirrhosis due to other causes [2].…”

“…Furthermore, so-call regenerative nodules in cirrhosis that are carved by progressive hepatic fibrous bands [2] are classified as macro-, micro-, and mixed-nodular cirrhosis, and also tends to depend on the etiologies of the cirrhosis [19]. However, as cirrhosis progresses, the characteristic histologic features of various etiologies may be lost, and the features of specific types of cirrhosis may be indistinguishable from cirrhosis due to other causes [2]. Thus, not only the differences of a variety of etiologies but also blood flow disorders may strongly influence confluent fibrosis.…”

“…During the progression of fibrosis, the accumulation of proteins in the extracellular matrix promotes the formation of scars that bridge together across adjacent portal triads and central veins, and ultimately, hepatic fibrosis can be demonstrated on computed tomography (CT) or magnetic resonance (MR) imaging as fibrotic septa and bridges in patients with end-stage liver disease [2,3].…”

“…Liver fibrosis is considered to be irreversible, but is regarded as a dynamic process with potential for regression [2].…”

Darbepoetin-α inhibits the perpetuation of necro-inflammation and delays the progression of cholestatic fibrosis in mice

“…This transition of epithelial cells and hepatocytes into fibroblasts has been reported as a possible source for extracellular matrix production. 5,30 It is of interest that the antifibrotic effect of DPO could not be confirmed at 28 days after BDL. The data could support the hypothesis that DPO rather delays than inhibits the profibrotic cascade.…”