| セッション情報 | The 8th JSGE-AGA Joint Meeting |
|---|---|
| タイトル | JM-1：Current and Future Anti-fibrotic Therapies for Chronic Liver Disease |
| 演者 | Rockey Don C.（Department of Internal Medicine, Medical University of South Carolina, USA） |
| 共同演者 | |
| 抄録 | Understanding the basic mechanisms underlying chronic liver disease will lead to novel therapies for this disease. Indeed, lessons from cell biology can be applied to cirrhosis and moreover, cirrhosis can be used as a model for basic cellular systems. A fundamental concept is that the response to recurrent injury, in the liver, and in other organs is one of wound healing. Extensive investigation over the past 20 years has established that the effector in the liver wound healing process is the hepatic stellate cell（also known as a lipocyte or Ito cell）. A central feature of the wounding response to liver injury is the transformation of resident stellate cells from a “quiescent”（normal）to an “activated”（injured liver）state. Characteristics of this transition include morphologic and functional changes. Morphologic changes include loss of vitamin A, acquisition of stress bundles, and development of prominent rough endoplasmic reticulum. One of the earliest described and most prominent effects of stellate cell activation is production of increased quantities of extracellular matrix, including types I, III and IV collagens, fibronectin, laminin and proteoglycans, some of which are increased by greater than 50-fold. Further, the available evidence now indicates that the overall increase in extracellular matrix protein deposition typical of cirrhosis can largely be ascribed to excess production by stellate cells. Thus, great emphasis has been placed on elucidating mechanisms underlying stimulation of fibrogenesis by stellate cells. A number of events, typically acting in concert, play a role in stimulating stellate cell fibrogenesis. These mechanistic insights have important implications for development of biomarkers and therapeutic approaches in the monitoring and treatment of hepatic fibrosis. A number of human studies have shown that effective treatment of the underlying disorder effectively reduces liver fibrosis（including hepatitis B, C, autoimmune hepatitis, alcoholic hepatitis, hemochromatosis, secondary biliary cirrhosis, etc…）. Further, human studies, typically based on sound preclinical investigation, have also explored directly acting anti-fibrotics（farglitizar, interferon gamma）；these compounds have unfortunately been found to be ineffective. Many other pathways have been identified and many will be translated into clinical studies. Thus, future studies will shed light on novel approaches and compounds that will likely exhibit anti-fibrotic activity. |
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