Bataller Ramón, Brenner David A
Liver Unit, Institut de Malalties Digestives i Metabòliques, Hospital Clinic, Institut d'Investigació Biomèdiques August Pi i Sunyer (IDIBAPS),Barcelona, Catalonia, Spain.
J Clin Invest. 2005 Feb;115(2):209-18. doi: 10.1172/JCI24282.
Liver fibrosis is the excessive accumulation of extracellular matrix proteins including collagen that occurs in most types of chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and often requires liver transplantation. Our knowledge of the cellular and molecular mechanisms of liver fibrosis has greatly advanced. Activated hepatic stellate cells, portal fibroblasts, and myofibroblasts of bone marrow origin have been identified as major collagen-producing cells in the injured liver. These cells are activated by fibrogenic cytokines such as TGF-beta1, angiotensin II, and leptin. Reversibility of advanced liver fibrosis in patients has been recently documented, which has stimulated researchers to develop antifibrotic drugs. Emerging antifibrotic therapies are aimed at inhibiting the accumulation of fibrogenic cells and/or preventing the deposition of extracellular matrix proteins. Although many therapeutic interventions are effective in experimental models of liver fibrosis, their efficacy and safety in humans is unknown. This review summarizes recent progress in the study of the pathogenesis and diagnosis of liver fibrosis and discusses current antifibrotic strategies.
肝纤维化是指在大多数慢性肝病中发生的细胞外基质蛋白(包括胶原蛋白)过度积聚。晚期肝纤维化会导致肝硬化、肝衰竭和门静脉高压,常常需要进行肝移植。我们对肝纤维化的细胞和分子机制的认识有了很大进展。活化的肝星状细胞、门静脉成纤维细胞以及骨髓来源的肌成纤维细胞已被确定为受损肝脏中主要的胶原蛋白产生细胞。这些细胞被诸如转化生长因子-β1、血管紧张素II和瘦素等促纤维化细胞因子激活。最近有文献记载了晚期肝纤维化在患者中的可逆性,这刺激研究人员开发抗纤维化药物。新兴的抗纤维化疗法旨在抑制促纤维化细胞的积聚和/或防止细胞外基质蛋白的沉积。尽管许多治疗干预措施在肝纤维化实验模型中有效,但其在人体中的疗效和安全性尚不清楚。本综述总结了肝纤维化发病机制和诊断研究的最新进展,并讨论了当前的抗纤维化策略。