The encephalopathy caused by acute liver failure is secondary to metabolic change that reverses completely after spontaneous recovery or salvage with liver transplantation. However, advanced encephalopathy in some patients is also associated with physical brain injury with the potential to cause irreversible brain damage or death. This is most commonly referred to as cerebral edema or intracranial hypertension, although it is now clear that the pathophysiology of this complication of acute liver failure is more complex than either of these descriptors suggests. Vascular changes include vasodilatation, loss of autoregulation, vasoconstriction, and loss of vascular elasticity. Brain tissue swelling further compromises vascular flow. Death in this situation may be by means of classical brain stem injury with herniation or coning through the foramen magnum. Alternatively, death or irreversible injury may result from hypoxia as a consequence of failure to maintain adequate blood supply and oxygen delivery to brain tissue.
The risk of cerebral edema is not uniform within the population of patients with acute liver failure. It occurs in patients with advanced encephalopathy, that is, patients who are at best responsive to painful stimuli. The incidence is highest in patients with more rapidly progressive disease and in an older study was detected in 70% of patients with hyperacute liver failure versus only 15% of patients with subacute liver failure. 1 Younger patients are more at risk of cerebral edema. 2 The incidence also appears to vary with etiology, and acetaminophen-induced acute liver failure and definable viral etiologies carry a higher risk, although it is not certain that this is independent of the categorization linked to the rate of progression of disease. 3