Autophagy in liver diseases

Autophagy or cellular self-digestion is a cellular pathway crucial for development differentiation survival and homeostasis Its implication in human diseases has been highlighted during the last decade Recent data show that autophagy is involved in major fields of hepatology In liver ischemia reperfusion injury autophagy mainly has a prosurvival activity allowing the cell for coping with nutrient starvation and anoxia During hepatitis B or C infection autophagy is also increased but subverted by viruses for their own benefit In hepatocellular carcinoma the autophagy level is decreased In this context autophagy has an anti-tumor role and therapeutic strategies increasing autophagy as rapamycin have a beneficial effect in patients Moreover in hepatocellular carcinoma Beclin-1 level an autophagy protein has a prognostic significance In alpha-1-antitrypsin deficiency the aggregation-prone ATZ protein accumulates in the endoplasmic reticulum This activates the autophagic response which aims at degrading mutant ATZ Some FDA-approved drugs which enhance autophagy and the disposal of aggregation-prone proteins may be useful in alpha-1-antitrypsin deficiency Following alcohol consumption autophagy is decreased in liver cells likely due to a decrease in intracellular 5'-AMP-activated protein kinase (AMPk) and due to an alteration in vesicle transport in hepatocytes This decrease in autophagy contributes to the formation of Mallory-Denk bodies and to liver cell death Hepatic autophagy is defective in the liver in obesity and its upregulation improves insulin sensitivity (C) 2010 European Association for the Study of the Liver Published by Elsevier B v All rights reserved