Hepatocyte apoptosis: Mechanisms and relevance in liver diseases

This chapter discusses the signaling mediators and regulators of hepatocyte apoptosis and the inclusion of injury stimulus-specific information within each mechanism. Hepatocyte apoptosis is a key mediator of liver injury and inflammation in most forms of liver disease. Multiple apoptotic pathways are activated by a given injurious stimulus in a vulnerable hepatocyte. Methodical dissection of pathways that mediate intracellular death signals demonstrates that lysosomes can be involved in the intrinsic pathway of cell death. Caspase activation, and apoptosis, is a highly regulated form of cell death, with multiple checkpoints and molecular mediators, activated via two distinct pathways, the extrinsic pathway and the intrinsic pathway. The extrinsic pathway is initiated via death receptor activation and the intrinsic pathway by intracellular perturbations that result in caspase activation. In hepatocytes, both pathways converge on mitochondria. Evidence of hepatocyte apoptosis can be demonstrated by serum markers and early studies demonstrate prognostic significance of apoptosis markers.