Dept. Clinical and Biological Sciences, Unit of Experimental Medicine and Clinical Pathology, University of Torino, Italy.
UCL Institute for Liver and Digestive Health, Division of Medicine - Royal Free Hospital, London, United Kingdom.
Mol Aspects Med. 2019 Feb;65:37-55. doi: 10.1016/j.mam.2018.09.002. Epub 2018 Sep 13.
The progression of chronic liver diseases (CLD), irrespective of etiology, involves chronic parenchymal injury, persistent activation of inflammatory response as well as sustained activation of liver fibrogenesis and wound healing response. Liver fibrogenesis, is a dynamic, highly integrated molecular, cellular and tissue process responsible for driving the excess accumulation of extracellular matrix (ECM) components (i.e., liver fibrosis) sustained by an eterogeneous population of hepatic myofibroblasts (MFs). The process of liver fibrogenesis recognizes a number of common and etiology-independent mechanisms and events but it is also significantly influenced by the specific etiology, as also reflected by peculiar morphological patterns of liver fibrosis development. In this review we will analyze the most relevant established and/or emerging pathophysiological issues underlying CLD progression with a focus on the role of critical hepatic cell populations, mechanisms and signaling pathways involved, as they represent potential therapeutic targets, to finally analyze selected and relevant clinical issues.
慢性肝脏疾病（CLD）的进展，无论病因如何，都涉及慢性实质损伤、炎症反应的持续激活以及肝纤维化和伤口愈合反应的持续激活。肝纤维化是一个动态的、高度整合的分子、细胞和组织过程，负责驱动细胞外基质（ECM）成分的过度积累（即肝纤维化），这是由一群异质性的肝肌成纤维细胞（MFs）所维持的。肝纤维化的形成过程识别出许多共同的、与病因无关的机制和事件，但也受到特定病因的显著影响，这也反映在肝纤维化发展的特殊形态模式上。在这篇综述中，我们将分析 CLD 进展背后最相关的已确立和/或新兴的病理生理问题，重点关注关键的肝细胞群体、涉及的机制和信号通路，因为它们代表潜在的治疗靶点，最后分析选定的相关临床问题。
