Abstract
Cerebral edema and hepatic encephalopathy are major complications of acute liver failure. Brain herniation caused by increased intracranial pressure as a result of cell swelling is the major cause of death in this condition. Evidence available currently suggests that the rapid accumulation of ammonia by the brain is the major cause of the central nervous system complications of acute liver failure. Increased brain ammonia may cause cell swelling via the osmotic effects of an increase in astrocytic glutamine concentrations or by inhibition of glutamate removal from brain extracellular space. Acute liver failure results in altered expression of several genes in brain, some of which code for important proteins involved in CNS function such as the glucose (GLUT‐1) and glutamate (GLT‐1) transporters, the astrocytic structural protein glial fibrillary acidic protein (GFAP) the “peripheral‐type” benzodiazepine receptor (PTBR) and the water channel protein, aquaporin IV. Loss of expression of GLT‐1 results in increased extracellular brain glutamate in acute liver failure. Experimental acute liver failure also results in post‐translational modifications of the serotonin and noradrenaline transporters resulting in increased extracellular concentrations of these monoamines. Therapeutic measures currently used to prevent and treat brain edema and encephalopathy in patients with acute liver failure include mild hypothermia and the ammonia‐lowering agent L‐ornithine‐L‐aspartate. © 2001 Wiley‐Liss, Inc.