Academic journal article Alcohol Research

Hepatic Encephalopathy

Academic journal article Alcohol Research

Hepatic Encephalopathy

Article excerpt

Hepatic encephalopathy (HE) is a brain disorder caused by chronic liver failure, particularly in alcoholics with cirrhosis, which results in cognitive, psychiatric, and motor impairments. In these patients, the number of functional liver cells is reduced, and some blood is diverted around the liver before toxins are removed. As a result, toxins such as ammonia and manganese can accumulate in the blood and enter the brain, where they can damage nerve cells and supporting cells called astrocytes. Positron emission tomography analyses have determined that ammonia levels are elevated in the brains of HE patients; ammonia accumulation can alter the expression of various important brain genes. Magnetic resonance images show that manganese is deposited in a brain area called the globus pallidus; manganese deposits may be responsible for structural changes in the astrocytes that are characteristic of HE. Treatment of patients with HE involves measures to lower ammonia levels in the blood, medications to counteract ammonia's effects on brain cell function, devices to compensate for liver dysfunction, and liver transplantation.

KEY WORDS: hepatic encephalopathy; toxic drug effect; neurotoxicity; alcoholic liver cirrhosis; symptom; diagnosis; brain damage; impaired balance and coordination; ammonia; manganese; neuroimaging; positron emission tomography; magnetic resonance imaging; drug therapy; dialysis; liver; organ transplantation

The liver and the brain interact in numerous ways to ensure normal brain functioning. For example, the liver plays a key role in supplying nutrients to the brain, which cannot produce these compounds itself. The liver also removes toxic substances from the blood, including substances that have been generated in the brain and must be eliminated from the body, as well as compounds produced in other tissues that are harmful to the brain's nerve cells (i.e., are neurotoxic). Thus, liver dysfunction can cause disturbances of brain function and even contribute to brain damage.

Liver dysfunction of varying severity is a frequent complication of chronic alcohol abuse. The most common and least severe form of alcoholic liver disease-fatty liver (stcatosis)-is characterized by fat deposits in the primary liver cells (i.e., the hepatocytes). More serious stages of alcoholic liver disease include inflammation of liver tissue (hepatitis), scar tissue formation (fibrosis), and destruction of the normal liver architecture (cirrhosis). When the liver becomes fibrotic and cirrhotic, the number of functional hepatocytes decreases, and the liver loses its capacity to remove toxic substances from the blood. Moreover, during these disease stages some of the blood entering the liver through the portal vein cannot penetrate the diseased liver and is diverted directly into the general circulation; this phenomenon is known as portal-systemic shunting. Blood that bypasses the liver is not detoxified, and blood levels of toxic substances increase. Researchers have identified several toxins that normally are removed in the liver but are found in the circulation of patients with alcoholic cirrhosis, including ammonia, manganese, and chemicals called mercaptans, all of which readily enter the brain and are neurotoxic. Consequently, brain function in patients with severe alcoholic liver disease is compromised, resulting in a condition known as hepatic encephalopathy (HE) or portal-systemic encephalopathy. '

This article describes the characteristics and diagnosis of HE and the changes in brain cell structure associated with this condition. The article also reviews imaging techniques that allow researchers to study changes in brain structure and function occurring in patients with HE and describes the contributions of ammonia and manganese to the development of HE, as elucidated by these techniques. Finally, the article explores some approaches currently used or being investigated for treating patients with HE resulting from alcoholic liver disease. …

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