Diletta Overi1, Guido Carpino2, Antonio Franchitto1, Paolo Onori 1, Eugenio Gaudio 1*
1 Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza Universityof Rome, 00161, Rome, Italy; diletta.overi@uniroma1.it; antonio.franchitto@uniroma1.it; paolo.onori@uniroma1.it; eugenio.gaudio@uniroma1.it.
2 Department of Movement, Human and Health Sciences, Division of Health Sciences, University of Rome ʺForo Italicoʺ, 00135, Rome, Italy; guido.carpino@uniroma1.it
* Correspondence: eugenio.gaudio@uniroma1.it; Tel.: +39‐06‐4991‐8062 (E.G.)
Received: date; Accepted: date; Published: date
Abstract: 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.
Keywords: liver; progenitor cell; regeneration; macrophage; disease; fibrosis; lipotoxicity; adipose tissue; atherosclerosis; ductular reaction.