肝纤维化的发病机制及治疗的最新进展

Recent progress in pathogenesis and treatment of liver fibrosis

肝纤维化是在各型肝炎病毒感染、酒精和脂肪性肝病、胆汁和自身免疫性肝病后发生的一种肝损伤后的慢性修复反应。在肝脏中,肝星状细胞(HSCs)的主要作用是激活肌成纤维细胞并产生细胞外基质(ECM)。大量的炎性和纤维性因子可以激活肝星状细胞。研究发现肝纤维化是可逆的,移除外源性致病因子后,激活的肝星状细胞可恢复至静息状态。虽然肝纤维化的基础研究有了显著进展,但作为非侵入性诊断工具的敏感和特异性生物标志物以及有效的抗纤维化药物尚未研发出来。本综述主要介绍了肝纤维化的细胞和分子机制以及治疗的最新进展,特别是关于肌成纤维细胞的来源、自噬、炎症因子和肝纤维化的可逆性等方面。

Liver fibrosis occurs in response to any etiology of chronic liver injury including hepatitis B and C,alcohol consumption,fatty liver disease,cholestasis,and autoimmune hepatitis.Hepatic stellate cells(HSCs)are the primary source of activated myofibroblasts that produce extracellular matrix(ECM)in the liver.Various inflammatory and fibrogenic pathways contribute to the activation of HSCs.Recent studies also discovered that liver fibrosis is reversible and activated HSCs can revert to quiescent HSCs when causative agents are removed.Although the basic research for liver fibrosis has progressed remarkably,sensitive and specific biomarkers as non-invasive diagnostic tools,and effective anti-fibrotic agents have not been developed yet.This review highlights the recent advances in cellular and molecular mechanisms of liver fibrosis,especially focusing on origin of myofibroblasts,autophagy,Inflammation and reversibility of liver fibrosis.