Volume 44, Issue 5, Pages 984-993 (May 2006) The role of apoptosis versus oncotic necrosis in liver injury: Facts or faith?  Henning Schulze-Bergkamen, Marcus Schuchmann, Binje Fleischer, Peter R. Galle  Journal of Hepatology  Volume 44, Issue 5, Pages 984-993 (May 2006) DOI: 10.1016/j.jhep.2006.02.004 Copyright © 2006 European Association for the Study of the Liver Terms and Conditions

Fig. 1 Modes of cell death in the liver. Hepatocytes can die from different modes of cell death. Apoptosis occurs in physiologic as well as pathologic conditions and represents a highly organized and genetically controlled type of cell death leading to shrinkage of the cell and disintegration into small apoptotic bodies. Paraptosis involves cytoplasmic vacuolation independent on caspase activity and in the absence of typical nuclear changes [68]. Its role in liver diseases is not yet defined. Necrosis (or oncosis/oncotic necrosis) leads to cellular edema and disruption of the cell membrane, e.g. in reperfusion liver injury. In autophagy, the cell's own lysosomal system leads to degradation of organelles and cell death. Breakdown of autophagy has been discussed to contribute to tumorigenesis in hepatocellular carcinoma [67]. Anoikis occurs if hepatocytes loose their contact to the extracellular matrix [73]. Mitotic catastrophe occurs after mitotic failure, but has not been described to contribute to liver injury so far [71]. FHF, fulminant hepatic failure; NASH, non-alcoholic steatohepatitis; ROS, reactive oxygen species; TNF, tumor necrosis factor. Journal of Hepatology 2006 44, 984-993DOI: (10.1016/j.jhep.2006.02.004) Copyright © 2006 European Association for the Study of the Liver Terms and Conditions

Fig. 2 Conflicting patterns of cell death in the liver. Inappropriate death of hepatocytes causes liver injury in different pathological conditions. However, the classic dichotomy between apoptosis and necrosis does not reflect the complexity of cell death patterns in liver injury. Apoptosis and necrosis can share features and mechanisms, which often makes discrimination difficult. ROS, reactive oxygen species. Journal of Hepatology 2006 44, 984-993DOI: (10.1016/j.jhep.2006.02.004) Copyright © 2006 European Association for the Study of the Liver Terms and Conditions

Fig. 3 Pro-survival strategies for the treatment of liver diseases. Over the past years, much effort has been devoted to the search of strategies to inhibit liver injury. Most of these efforts target apoptosis pathways, such as inhibition of caspases and death receptor signaling. KC, Kupffer cells; HSC, hepatic stellate cells; cIAP, cellular inhibitors of apoptosis; DISC, death inducing signaling complex. Journal of Hepatology 2006 44, 984-993DOI: (10.1016/j.jhep.2006.02.004) Copyright © 2006 European Association for the Study of the Liver Terms and Conditions

Fig. 4 Pitfalls of anti-apoptotic therapy strategies liver diseases. Targeting death pathways in the liver represents a powerful tool for the treatment of liver diseases. However, some potential side effects should be considered. Senescence: a signal transduction program leading to irreversible cell cycle arrest. HSC, hepatic stellate cells. Journal of Hepatology 2006 44, 984-993DOI: (10.1016/j.jhep.2006.02.004) Copyright © 2006 European Association for the Study of the Liver Terms and Conditions