الفهرس 
Genetic Determinants in Hepatic FibrosisOnly 14 pages are availabe for public view
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Abstract
The objectives of the present essay are to review and discuss the current concepts on: Genetic determinant, The pathogenesis, Diagnosis (non-invasive methods), and Treatment of liver fibrosis.
Hepatic fibrosis is a nonspecific reaction in response to chronic liver injury. Genetic factors play important roles in the modulation of hepatic fibrosis and contribute to the variability in fibrosis progression.
HSCs had been shown to be the source of fibrillar collagens and basement membrane proteins. HSCs considered to be important myofibroblast precursors in the diseased liver; HSCs are the dominant fibrogenic cells in all forms of fibrosis. Other mesenchymal cell populations, most notably portal fibroblasts and circulating cells from the bone marrow, are emerging as significant matrix-producing cells. Hepatocytes and BECs are hypothesized to undergo EMT and participate in fibrogenesis in the form of myofibroblasts.
The contractile force generated by stellate cells within the liver may contribute to the development of hepatic fibrosis by modulating sinusoidal blood flow and participating in extracellular matrix remodeling. Hepatic fibrosis is the result of a complex interplay between resident hepatic cells, infiltrating inflammatory cells, and several locally acting peptides called cytokines. Dysregulated cytokine release underlies the hepatic response to injury and participates in the initiation, progression, and maintenance of fibrosis. Key mediators include TGF-β1, vasoactive substances, adipokines, and several inflammatory cytokines and chemokines.
Accumulating evidence indicates that angiotensin II, the main effector of the RAS, is a true cytokine that plays a major role in liver fibrosis. An intrahepatic RAS is expressed in chronically damaged livers, and angiotensin II induces an array of fibrogenic actions in hepatic stellate cells, including increased collagen synthesis and secretion of inflammatory mediators. These effects are mediated by NADPH oxidase–generated ROS and are prevented by angiotensin type 1 receptor blockers. Inhibition of the RAS markedly attenuates experimentally induced liver fibrosis in rodents.
The diagnosis of liver fibrosis using noninvasive tools is important for epidemiologic, prognostic, therapeutic, pragmatic, and economical reasons. Noninvasive tests for liver fibrosis are broadly divided into blood tests, imaging, and novel technologies. Noninvasive tests have concentrated on defining fibrosis at a fixed point, and the ability to define severe disease is excellent. The serial and combination use of different noninvasive tests has continued to improve performance and increased the ability to classify more patients and maintain accuracy. The use of clinical end points and longitudinal measurement are promising areas of development and will probably show the true potential of noninvasive tests.
A further critical concept is that even advanced fibrosis is dynamic and may be reversible. Currently, the most effective therapy for hepatic fibrogenesis is to attenuate or clear the underlying disease. The most effective specific antifibrotic therapies will most likely be directed at fibrogenic effector cells. Although no specific, effective, safe, and inexpensive antifibrotic therapies are yet available, multiple potential targets have been identified and effective therapies are expected to emerge.