Pathogenesis of Hepatic Encephalopathy in Acute Liver Failure

Javier Vaquero, MD, Chuhan Chung, MD, Michael E. Cahill, BA, Andres T. Blei, MD


Semin Liver Dis. 2003;23(3) 

In This Article

Abstract and Introduction


Hepatic encephalopathy (HE) in acute liver injury signifies a serious prognosis. Brain edema and intracranial hypertension are major causes of death in this syndrome. Comparison of HE in acute liver failure (ALF) with that of cirrhosis allows recognition of important differences and similarities. A key role for ammonia in the pathogenesis of both HE and brain edema is now firmly supported by clinical and experimental data. Additional factors, such as infection, products of the necrotic liver, and synergistic toxins, may contribute to an altered mental state. A low plasma osmolarity, high temperature, and both high and low arterial pressure may affect brain water content. A combined derangement of cellular osmolarity coupled with cerebral hyperemia can explain the development of brain edema in ALF. Increasingly, study of the mechanisms responsible for brain swelling provides critical information for understanding the pathogenesis of HE.


The development of HE in patients with ALF signals a critical phase of the illness (also defined as fulminant hepatic failure)[1] and is associated with a reduced survival. In epidemiological studies performed in the pretransplant era, spontaneous recovery of liver function was 70% in stages I and II encephalopathy and was reduced to < 20% in stages III and IV encephalopathy.[2] Death in hepatic coma is common in patients with cirrhosis and advanced liver failure, but a unique feature of ALF is death from cerebral edema and intracranial hypertension.