Acute liver failure: Mechanisms of hepatocyte injury and regeneration

Acute liver failure (ALF) occurs when the extent of hepatocyte death exceeds the liver's regenerative capacity. Despite vast differences in causes, the mode of cell death typically follows one of two patterns: necrosis or apoptosis. Necrosis and apoptosis have traditionally been considered separate entities within various etiologies of ALF; however, there is increasing evidence that they are alternative outcomes of the same initiating factors and signaling pathways, a process known as necroapoptosis. Here we review mechanisms of liver cell injury in ALF, including evolving knowledge of pathways leading to apoptosis, necrosis, and necroapoptosis, as well as how these pathways are potential therapeutic targets in ALF. We also discuss hepatic regeneration and the cytokines and growth factors involved in both the replication of differentiated hepatocytes as well as activation of intrahepatic progenitor cells, two pathways of hepatocyte regeneration that are dependent on the type and extent of hepatic insult in ALF.