Hepatic encephalopathy as a complication of liver disease.

Abstract

Hepatic encephalopathy (HE) is a frequent complication of chronic liver disease. It is defined as a characteristic functional and reversible alteration of the mental state, due to impaired liver function and/or increased portosystemic shunting. In the brain of HE patients, neurons appear morphologically normal, but astrocytes show signs of Alzheimer type II degeneration, i.e. nuclear enlargement, peripheral margination of chromatin and prominent nucleoli. Ammonia is generally considered to play a central role in the pathophysiology of HE[1]. In HE, selective alterations of blood-brain barrier permeability, changes in cerebral energy metabolism, an increased GABA-ergic tone, changes in neurotransmitter systems and alterations of gene expression. e.g. of monoamine oxidase, peripheral-type benzodiazepine receptor (PTBR) and neuronal NO synthase are found (reviewed in[1-10]. The reversibility of HE symptoms and the reason for its precipitation by a variety of different factors has not been sufficiently explained yet (Table ​(Table1).1). Central insights into the etiology of HE have arisen from recent in vitro work with astrocytes. Astrocytes are important constituents of the blood-brain barrier, and uptake of substances from the blood into the brain is achieved by transastrocytic transport. Astrocytes communicate directly with neurons[11], regulate neurotransmitter processing and ionic milieu and provide substrates for neurons[12,13]. In brain, astrocytes are the only cells containing glutamine synthetase[14] and represent the major site of cerebral ammonia detoxification. Upon exposure to ammonia, cultured astrocytes develop Alzheimer type II changes. These findings prompted the idea that HE is a disorder of glial cells with a consecutive neuronal dysfunction[7,15,16]. Table 1 Precipitating factors of HE