targetingliverfibros.doc

Targeting Liver Fibrosis: Strategies for Development and Validation of Antifibrotic Therapies 针对肝纤维化：抗纤维化治疗的发展和检验的策略 We have made striking progress in our understanding of the biochemistry and cell biology that underlies liver fibrosis and cirrhosis, including the development of strategies and agents to prevent and reverse fibrosis. 我们已经在现今的生物化学和细胞生物学上构成肝脏纤维变性和肝硬变的However, translation of this knowledge into clinical practice has been hampered by 但是，把这种理论应用到临床实践上受到了阻碍： the limitation of many in vitro and in vivo models to confirm mechanisms and to test antifibrotic agents, （1）许多体外和体内模型机制and (2) the lack of sensitive methodologies to quantify the degree of liver fibrosis and the dynamics of fibrosis progression or reversal in patients. （2）缺乏量化肝纤维化程度和肝纤维化的动态进展Furthermore, whereas cirrhosis and subsequent decompensation are accepted hard clinical endpoints, fibrosis and fibrosis progression alone are merely plausible surrogates for future clinical deterioration. 此外，尽管肝硬化和随后的失代偿期被认为是临床终末阶段，但是肝纤维化和肝纤维化进程仅仅是未来临床恶化的In this review we focus on an optimized strategy for preclinical antifibrotic drug development and highlight the current and future techniques that permit noninvasive assessment and quantification of liver fibrosis and fibrogenesis. 这，为临床前抗肝纤维化药物开发优化，当前和未来非侵入性评估和量化肝纤维化纤维形成的技术The availability of such noninvasive methodologies will serve as the pacemaker for the clinical development and validation of potent antifibrotic agents. 这种非侵入性方法的将成为临床开发Fibrosis is an excessive wound healing response that occurs in most forms of chronic liver disease and results in the deposition of scar tissue, 肝纤维化是一种发生在大多数慢性肝病过度的伤口愈合的反应导致瘢痕组织沉积 i.e., excess extracellular matrix (ECM). 也就是细胞外基质的过度沉积。 With ongoing liver damage, fibrosis may progress to cirrhosis, which is characterized by a distortion of the liver vasculature and architecture, 随着持续的肝损伤，纤维化可发展肝硬化and which is the major determinant of morbidity and mortality in patients with liver disease, 肝病患者发病率和死亡率predisposing to l