The role of apoptosis versus oncotic necrosis in liver injury: Facts or faith?

A tightly controlled balance between cell division and cell death is a basic feature for the development and maintenance of liver homeostasis. Disturbances of this balance contribute to liver diseases: too much cell death can cause liver injury, too little cell death is a prerequisite for the development of hepatocellular carcinoma. Thus, a stringent control of the equilibrium of life and death in the liver is necessary. During the last decade most research activities in hepatology dealing with liver injury focussed on the evaluation of apoptosis pathways. Therefore, our understanding of the mechanisms of apoptosis has made profound progress. Programmed cell death (PCD) in the liver enables the physiological turnover of hepatocytes and the efficient removal of unwanted cells such as aged or virus-infected cells. Fulminant hepatic failure (FHF) and hepatocellular carcinoma are prototypical settings with uncontrolled massive apoptosis on the one hand, or resistance to apoptosis on the other hand. In addition to 'classical apoptosis', there is accumulating evidence that liver cells can die via PCD without typical features of apoptosis such as caspase activation. Various forms of caspase-independent cell death have been described, depicted as paraptosis, autophagy, mitotic catastrophe and others (Fig. 1). © 2006 European Association for the Study of the Liver.