Pathogenesis of liver injury and hepatic fibrosis in Non-Alcoholic SteatoHepatitis, NASH

非酒精性脂肪性肝炎、NASH 肝损伤和肝纤维化的发病机制

• 批准号: nhmrc : 153899
• 负责人: A/Pr Graham Robertson
• 金额: $ 29.21万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/pathogenesis-liver-injury-steatohepatitis-nash/77677
• 关键词: Pathogenesis; liver; injury; hepatic; fibrosis

Nonalcoholic steatohepatitis (NASH) is the most common form of liver disease in affluent countries. In Australia at least 3% of the population and 20% of those with obesity have NASH. This poorly understood disease covers a spectrum of liver disorders - from relatively benign presence of excess fat in the liver - to cirrhosis and liver failure. This pattern of liver damage is virtually identical to alcoholic hepatitis, however alcohol consumption is excluded in NASH. It is often associated with type II diabetes , obesity and lipid disorders. Although fatty liver by itself is thought to be innocuous and reversible, a small number of cases with this mild syndrome progress to a more severe form of NASH. One aim of this project is to identify and characterise the factors which trigger injury in a fatty liver and lead to the destruction of liver cells. In response to the initial liver injury in NASH, cells in the liver and from the immune system mount an inflammatory reaction. However this may make the liver even more susceptible to further injury by amplifying the effect of the initial insult. The inflammatory response is controlled by key signalling molecules produced by specific liver and immune cells. The second aim of this project is to identify such molecules and their cellular source and to determine whether they perpetuate the disease processes of NASH. One outcome of liver injury and the consequent inflammatory reaction is that the liver repairs the damage by forming fibres of scar tissue in a process similar to wound healing. When unchecked this process of fibrosis leads to cirrhosis and the development of severe liver complications. The final aim is to gain new insights into the links between liver cell injury, the inflammatory response and fibrosis which will eventually lead to treatments to prevent the initial triggers of this disease and also to interrupt the progression of NASH to more serious fibrotic stage.

非酒精性脂肪性肝炎（NASH）是富裕国家最常见的肝病。在澳大利亚，至少 3% 的人口和 20% 的肥胖者患有 NASH。 This poorly understood disease covers a spectrum of liver disorders - from relatively benign presence of excess fat in the liver - to cirrhosis and liver failure.这种肝损伤模式实际上与酒精性肝炎相同，但 NASH 不包括饮酒。它通常与 II 型糖尿病、肥胖和血脂紊乱有关。尽管脂肪肝本身被认为是无害且可逆的，但少数患有这种轻度综合征的病例会发展为更严重的 NASH。该项目的目的之一是识别和描述引发脂肪肝损伤并导致肝细胞破坏的因素。为了应对 NASH 最初的肝损伤，肝脏细胞和免疫系统细胞会产生炎症反应。然而，这可能会放大最初损伤的影响，从而使肝脏更容易受到进一步损伤。炎症反应由特定肝脏和免疫细胞产生的关键信号分子控制。该项目的第二个目标是识别此类分子及其细胞来源，并确定它们是否使 NASH 疾病过程永久化。肝损伤和随之而来的炎症反应的结果之一是，肝脏通过形成疤痕组织纤维来修复损伤，其过程类似于伤口愈合。如果不加以控制，这种纤维化过程会导致肝硬化和严重肝脏并发症的发生。最终目标是对肝细胞损伤、炎症反应和纤维化之间的联系获得新的见解，最终将导致治疗方法预防这种疾病的最初触发因素，并阻止 NASH 进展到更严重的纤维化阶段。