Magdaleno Fernando, Schierwagen Robert, Uschner Frank E, Trebicka Jonel
Department of Internal Medicine I, University of Bonn, Bonn, Germany.
Department of Internal Medicine I, University of Bonn, Bonn, Germany -
Minerva Gastroenterol Dietol. 2018 Mar;64(1):51-61. doi: 10.23736/S1121-421X.17.02442-4. Epub 2017 Sep 11.
Fibrosis development was initially conceived as an incessant progressive condition. Nowadays, it has become evident that fibrotic tissue undergoes a continuous two-way process: fibrogenesis and fibrinolysis, characterizing the remodeling of extracellular matrix (ECM). However, in established fibrosis, this two-way process is tipped towards fibrogenesis and this leads to a self-perpetuating accumulation of ECM, a distinct metabolic unit, together with other cells and processes promoting fibrosis deposition. Several mechanisms promote fibrosis regression, such as degradation of ECM, infiltration of restorative macrophages, prevention of the epithelial-mesenchymal transition of hepatocytes, restoration of the liver sinusoidal endothelial cells' differentiation phenotype, and reversion to quiescence, apoptosis and senescence of hepatic stellate cells (HSC). Hence, fibrosis is the result of an unbalanced two-way process of matrix remodeling. At the late stage of the disease, antifibrotic interventions could become necessary to reverse self-perpetuating fibrogenesis and accelerate regression of fibrosis even if cause and cofactors of hepatic injury have been eliminated. This review outlines some of the important mechanisms leading towards regression of liver fibrosis.
纤维化发展最初被认为是一种持续进展的病症。如今，已明确纤维化组织经历着一个持续的双向过程：纤维生成和纤维溶解，这是细胞外基质（ECM）重塑的特征。然而，在已形成的纤维化中，这个双向过程倾向于纤维生成，这导致ECM的自我持续积累，ECM是一个独特的代谢单元，连同其他促进纤维化沉积的细胞和过程一起。几种机制促进纤维化消退，例如ECM降解、修复性巨噬细胞浸润、防止肝细胞上皮-间质转化、恢复肝窦内皮细胞的分化表型以及肝星状细胞（HSC）恢复静止、凋亡和衰老。因此，纤维化是基质重塑不平衡双向过程的结果。在疾病晚期，即使肝损伤的病因和辅助因素已被消除，抗纤维化干预可能仍有必要，以逆转自我持续的纤维生成并加速纤维化消退。本综述概述了一些导致肝纤维化消退的重要机制。
