The Role of Liver Disease in Alcohol-Induced Cognitive Defects

Chronic severe liver disease (i.e., cirrhosis) is a common complication of chronic alcohol abuse. Cirrhosis can cause brain dysfunction, most notably the disorder portal-systemic encephalopathy (PSE), which is characterized by cognitive and motor dysfunction and, eventually, by hepatic coma. Restoration of normal liver function-for example, through liver transplantation-can reverse some of the symptoms of PSE. PSE is caused by the shunting of venous blood into the general circulation without prior detoxification in the liver, allowing neurotoxins to reach the brain. The most prominent neurotoxin is ammonia. It interferes with the function of different brain cells and the communication between them. Ammonia and other toxins reaching the brain in PSE patients affect several neurotransmitters, including glutamate and monoamines.