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Am J Physiol Cell Physiol. 2017 Mar 1;312(3):C263-C273. doi: 10.1152/ajpcell.00295.2016. Epub 2016 Nov 30.

Autophagy in chronic liver diseases: the two faces of Janus.

Author information

1
Inserm-U1065, C3M, Team 8 "Hepatic complications in obesity," Nice, France.
2
Université Nice Côte d'Azur, Inserm, C3M, Nice, France.
3
Institut Cochin, Inserm-U1016, CNRS UMR 8104, Université Paris-Descartes, Paris, France.
4
Inserm-U1149, CNRS-ERL8252, Centre de Recherche sur l'Inflammation, Paris, France; and sophie.lotersztajn@inserm.fr.
5
Sorbonne Paris Cité, Laboratoire d'Excellence Inflamex, Faculté de Médecine, Site Xavier Bichat, Université Paris Diderot, Paris, France.

Abstract

Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are the leading causes of cirrhosis and increase the risk of hepatocellular carcinoma and liver-related death. ALD and NAFLD share common pathogenic features extending from isolated steatosis to steatohepatitis and steatofibrosis, which can progress to cirrhosis and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of NAFLD and ALD are complex and still unclear. Important links between the regulation of autophagy (macroautophagy and chaperone-mediated autophagy) and chronic liver diseases have been reported. Autophagy may protect against steatosis and progression to steatohepatitis by limiting hepatocyte injury and reducing M1 polarization, as well as promoting liver regeneration. Its role in fibrosis and hepatocarcinogenesis is more complex. It has pro- and antifibrogenic properties depending on the hepatic cell type concerned, and beneficial and deleterious effects on hepatocarcinogenesis at initiating and late phases, respectively. This review summarizes the latest advances on the role of autophagy in different stages of fatty liver disease progression and describes its divergent and cell-specific effects during chronic liver injury.

KEYWORDS:

ALD; NAFLD; autophagy; fibrosis; hepatocellular carcinoma; inflammation; liver; regeneration; steatosis

PMID:
27903585
DOI:
10.1152/ajpcell.00295.2016
[Indexed for MEDLINE]
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