Cerebral edema and liver disease: Classic perspectives and contemporary hypotheses on mechanism.

Liver disease is a growing public health concern. Hepatic encephalopathy, the syndrome of brain dysfunction secondary to liver disease, is a frequent complication of both acute and chronic liver disease and cerebral edema (CE) is a key feature. While altered ammonia metabolism is a key contributor to hepatic encephalopathy and CE in liver disease, there is a growing appreciation that additional mechanisms contribute to CE. In this review we will begin by presenting three classic perspectives that form a foundation for a discussion of CE in liver disease: 1) CE is unique to acute liver failure, 2) CE in liver disease is only cytotoxic, and 3) CE in liver disease is primarily an osmotically mediated consequence of ammonia and glutamine metabolism. We will present each classic perspective along with more recent observations that call in to question that classic perspective. After highlighting these areas of debate, we will explore the leading contemporary mechanisms hypothesized to contribute to CE during liver disease.