非酒精性脂肪性肝病(NAFLD)正在达到流行病的比例,全球成人患病率为25%。非酒精性脂肪性肝炎(NASH),会导致肝硬化,已经成为欧洲和美国肝移植的主要适应症。肝纤维化是持续的结果,迭代肝损伤,以及NASH结局的主要决定因素。肝脏具有显著的内在可塑性,肝纤维化可以在去除有害物质后消退,从而提供了通过治疗干预改变长期结局的机会.尽管肝细胞损伤是NASH的关键驱动因素,肝纤维化小生境内的多个其他细胞系在炎症的延续中起主要作用,间充质细胞活化,细胞外基质积累以及纤维化分辨率。这种细胞相互作用的成分,以及纤维化小生境中的各种亚群如何相互作用以驱动纤维发生是一个活跃的研究领域。纤维化小生境的重要细胞成分包括内皮细胞,巨噬细胞,传代免疫细胞群和肌成纤维细胞。在这次审查中,我们将描述单细胞基因组学等技术的快速发展,空间转录组学和单细胞配体受体分析正在改变我们对NAFLD/NASH细胞相互作用组的理解,以及这个新的,利用高分辨率信息为NASH患者开发合理的新疗法.
Non-alcoholic fatty liver disease (NAFLD) is reaching epidemic proportions, with a global prevalence of 25% in the adult population. Non-alcoholic steatohepatitis (NASH), which can lead to cirrhosis, has become the leading indication for liver transplantation in both Europe and the USA. Liver fibrosis is the consequence of sustained, iterative liver injury, and the main determinant of outcomes in NASH. The liver possesses remarkable inherent plasticity, and liver fibrosis can regress when the injurious agent is removed, thus providing opportunities to alter long-term outcomes through therapeutic interventions. Although hepatocyte injury is a key driver of NASH, multiple other cell lineages within the hepatic fibrotic niche play major roles in the perpetuation of inflammation, mesenchymal cell activation, extracellular matrix accumulation as well as fibrosis resolution. The constituents of this cellular interactome, and how the various subpopulations within the fibrotic niche interact to drive fibrogenesis is an area of active research. Important cellular components of the fibrotic niche include endothelial cells, macrophages, passaging immune cell populations and myofibroblasts. In this review, we will describe how rapidly evolving technologies such as single-cell genomics, spatial transcriptomics and single-cell ligand-receptor analyses are transforming our understanding of the cellular interactome in NAFLD/NASH, and how this new, high-resolution information is being leveraged to develop rational new therapies for patients with NASH.