Death receptor-mediated apoptosis and the liver

Apoptosis is an essential feature contributing to liver injury in a wide range of acute and chronic liver diseases. With an improved understanding of the pathophysiological role of apoptosis in liver diseases, we are now entering an era where modulation of apoptosis is becoming a therapeutic possibility. For example, the differential sensitivity of virally infected hepatocytes to TRAIL-induced apoptosis could therapeutically be useful for removing hepatocytes bearing viral nucleic acids, or selective induction of apoptosis in activated hepatic stellate cells may be an ideal anti-fibrotic therapeutic strategy. Inhibition of hepatocyte apoptosis using a variety of different strategies may also be therapeutically beneficial in liver injuries, such as alcoholic hepatitis, cholestatic liver disease and Wilson's disease. Moreover, considering the link between the hepatocyte apoptosis and the liver fibrosis, inhibition of hepatocyte apoptosis may also be an anti-fibrotic therapeutic strategy. These concepts, in our opinion, merit further clinical and basic investigation.