Mechanisms of hepatocyte injury, multiorgan failure, and prognostic criteria in acute liver failure.

Acute liver failure (ALF) occurs when the rate and extent of liver cell death are not adequately balanced by regenerative activity. Two forms of liver cell death are recognized: apoptosis and necrosis. A number of causes of ALF have been shown, predominantly in experimental animal models, to induce one or the other form of liver cell death. Nonetheless, an insult capable of inducing apoptosis may cause cell death by necrosis, particularly if the degree of mitochondrial damage is sufficient to exhaust stores of adenosine triphosphate. Here we consider mechanisms of liver cell injury in ALF, including evolving knowledge of signaling pathways leading to hepatocellular apoptosis and necrosis. Factors that have an impact on the adequacy of hepatic regeneration along with the pathophysiology of complicating multiorgan failure are also reviewed. Prognostic criteria are discussed, especially in relation to current concepts of mechanisms of liver cell death and multiorgan dysfunction.