Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, 00161 Rome, Italy.
Department of Movement, Human and Health Sciences, Division of Health Sciences, University of Rome "Foro Italico", 00135 Rome, Italy.
Cells. 2020 Mar 2;9(3):590. doi: 10.3390/cells9030590.
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by lipid accumulation in hepatocytes in the absence of excessive alcohol consumption. The global prevalence of NAFLD is constantly increasing. NAFLD is a disease spectrum comprising distinct stages with different prognoses. Non-alcoholic steatohepatitis (NASH) is a progressive condition, characterized by liver inflammation and hepatocyte ballooning, with or without fibrosis. The natural history of NAFLD is negatively influenced by NASH onset and by the progression towards advanced fibrosis. Pathogenetic mechanisms and cellular interactions leading to NASH and fibrosis involve hepatocytes, liver macrophages, myofibroblast cell subpopulations, and the resident progenitor cell niche. These cells are implied in the regenerative trajectories following liver injury, and impairment or perturbation of these mechanisms could lead to NASH and fibrosis. Recent evidence underlines the contribution of extra-hepatic organs/tissues (e.g., gut, adipose tissue) in influencing NASH development by interacting with hepatic cells through various molecular pathways. The present review aims to summarize the role of hepatic parenchymal and non-parenchymal cells, their mutual influence, and the possible interactions with extra-hepatic tissues and organs in the pathogenesis of NAFLD.
非酒精性脂肪性肝病（NAFLD）是一种以肝细胞内脂质蓄积为特征的慢性肝脏疾病，而不存在过量饮酒。全球范围内 NAFLD 的患病率持续上升。NAFLD 是一种疾病谱，包含不同预后的不同阶段。非酒精性脂肪性肝炎（NASH）是一种进行性疾病，其特征为肝脏炎症和肝细胞气球样变，伴有或不伴有纤维化。NASH 的发生和向晚期纤维化的进展对 NAFLD 的自然病程产生负面影响。导致 NASH 和纤维化的发病机制和细胞相互作用涉及肝细胞、肝巨噬细胞、肌成纤维细胞亚群和固有祖细胞龛。这些细胞参与肝脏损伤后的再生轨迹，这些机制的损害或紊乱可能导致 NASH 和纤维化。最近的证据强调了肝外器官/组织（例如肠道、脂肪组织）通过各种分子途径与肝细胞相互作用，对 NASH 发展的影响。本综述旨在总结肝实质细胞和非实质细胞的作用、它们之间的相互影响以及与肝外组织和器官的可能相互作用在 NAFLD 发病机制中的作用。
