Journal
JOURNAL OF HEPATOLOGY
Volume 70, Issue 5, Pages 985-998Publisher
ELSEVIER
DOI: 10.1016/j.jhep.2019.01.026
Keywords
Autophagy; Fibrosis; Inflammation; Hepatocyte apoptosis; NASH; Hepatocellular carcinoma; Alcoholic liver disease
Categories
Funding
- INSERM (France)
- Universite Paris-Diderot and Paris Descartes, Labex Inflamex
- Fondation pour la Recherche Medicale (FRM) [DEQ20150331726]
- National Research Agency [ANR-18-CE14-0006]
- Poste d'Accueil INSERM
- Agence Nationale de la Recherche (ANR) [ANR-18-CE14-0006] Funding Source: Agence Nationale de la Recherche (ANR)
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Autophagy is a self-eating catabolic pathway that contributes to liver homeostasis through its role in energy balance and in the quality control of the cytoplasm, by removing misfolded proteins, damaged organelles and lipid droplets. Autophagy not only regulates hepatocyte functions but also impacts on non-parenchymal cells, such as endothelial cells, macrophages and hepatic stellate cells. Deregulation of autophagy has been linked to many liver diseases and its modulation is now recognized as a potential new therapeutic strategy. Indeed, enhancing autophagy may prevent the progression of a number of liver diseases, including storage disorders (alpha-1 antitrypsin deficiency, Wilson's disease), acute liver injury, non-alcoholic steatohepatitis and chronic alcohol-related liver disease. Nevertheless, in some situations such as fibrosis, targeting specific liver cells must be considered, as autophagy displays opposing functions depending on the cell type. In addition, an optimal therapeutic time-window should be identified, since autophagy might be beneficial in the initial stages of disease, but detrimental at more advanced stages, as in the case of hepatocellular carcinoma. Finally, identifying biomarkers of autophagy and methods to monitor autophagic flux in vivo are important steps for the future development of personalized autophagy-targeting strategies. In this review, we provide an update on the regulatory role of autophagy in various aspects of liver pathophysiology, describing the different strategies to manipulate autophagy and discussing the potential to modulate autophagy as a therapeutic strategy in the context of liver diseases. (C) 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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