肝纤维化的分子基础与临床诊治现状

Molecular basis of hepatic fibrosis and current status of its diagnosis and treatment

慢性肝损伤时,肝星状细胞与肝实质细胞、Kupffer细胞、肝窦内皮细胞等多种细胞相互作用,介导细胞外基质沉积与肝窦毛细血管化,启动肝纤维化进程,其本质是肝损伤后的修复反应。肝穿刺活组织检查技术是肝纤维化诊断的金标准,但有一定出血风险及死亡风险。无创性诊断肝纤维化的手段主要包括血清分子标志物、影像学诊断技术以及预测性统计模型等,但其尚不能完全替代肝穿刺活组织检查。目前,肝纤维化的治疗主要针对原发疾病、以肝星状细胞为靶点的药物研发、以细胞外基质合成/降解平衡为靶点的药物研发等方面。研究肝纤维化分子机制,为探索肝纤维化治疗提供了坚实的理论基础。

During the process of acute or chronic liver injury,hepatic stellate cells interact with various types of cells such as hepatic parenchymal cells,Kupffer cells,and liver sinusoidal endothelial cells to mediate extracellular matrix deposition and sinusoid capillarization and thus initiate the process of hepatic fibrosis.The nature of hepatic fibrosis is repair response after liver injury.Liver biopsy is regarded as the gold standard for the diagnosis of hepatic fibrosis;however,it is generally associated with the risk of bleeding and even death.Noninvasive diagnostic methods for liver fibrosis mainly include serum biomarkers,imaging techniques,and predictive statistical model,but such methods cannot completely replace liver biopsy.At present,the treatment of hepatic fibrosis focuses on the research and development of new drugs targeting primary disease,hepatic stellate cells,or balance of extracellular matrix synthesis/degradation.The research on the molecular mechanism of hepatic fibrosis provides a solid theoretical basis for exploring the treatment of hepatic fibrosis.