Apoptosis and necroptosis in the liver: a matter of life and death

Abstract

<p class="first" id="P2">Cell death represents a basic biological paradigm that governs outcomes and long-term sequelae in almost every hepatic disease condition. Acute liver failure is characterized by massive loss of parenchymal cells but is usually followed by <i>restitution ad integrum</i>. By contrast, cell death in chronic liver diseases often occurs at lesser extents but leads to long-term alterations in organ architecture and function, contributing to chronic hepatocyte turnover, the recruitment of immune cells and activation of hepatic stellate cells, and thereby to the development of liver fibrosis, cirrhosis and cancer. It has become evident that besides apoptosis, necroptosis represents a highly relevant form of programmed cell death (PCD) in the liver. Differential activation of specific forms of PCD might not only affect outcomes in liver diseases, but also offer novel opportunities for therapeutic intervention. Here, we will summarize the underlying molecular mechanisms and open questions about disease-specific activation and roles of PCD forms, their contribution to response signatures as well as their detection. We will focus on the role of apoptosis and necroptosis in acute liver injury, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) and liver cancer, and possible translation into clinical applications. </p>