Hepatic encephalopathy

Abstract

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.

Figure 1

Brain cells called astrocytes from a 51-year-old alcoholic patient with cirrhosis who died in a coma (hepatic encephalopathy [HE]). The image shows both normal astrocytes (N), which have dark nuclei, and Alzheimer type II astrocytes (Alz), characteristic of HE, which have pale, enlarged nuclei. SOURCE: Modified from Butterworth 2002.

Figure 2

Positron emission tomography (PET) analyses of a healthy person and a 47-year-old alcoholic cirrhotic patient with mild hepatic encephalopathy. The blood flow through the brain (i.e., cerebral blood flow [CBF]) differs only minimally between the two subjects. However, the cerebral metabolic rate for ammonia (CMRA) and the permeability–surface area product (PS)—a measure of the extent to which ammonia can pass the blood–brain barrier and enter the brain—are significantly increased in the alcoholic patient, as indicated by the wider distribution and enhanced brightness of the light areas. SOURCE: Modified from Lockwood et al. 1991.

Figure 3

Magnetic resonance imaging (MRI) of a healthy control subject (C) and an alcoholic cirrhotic patient of the same age (P). In the alcoholic patient, abnormally intense signals (arrow) are detected on both sides of the brain in a region called the globus pallidus. This phenomenon has been attributed to deposits of manganese in this brain area. SOURCE: Lockwood et al. 1997.