Gut-derived Toxins Research Articles

Treatment of Chronic Hepatic Encephalopathy

The neuropsychiatric abnormalities which accompany cirrhosis of the liver vary widely from subclinical impairment of psychometric performance to overt episodic or persistent changes in cerebral function. The pathogenesis of the syndrome is unknown although important rôles are ascribed to circulating gut-derived toxins of nitrogenous origin and to changes in central neurotransmission, particularly of the dopaminergic and GABA-ergic systems. Treatment is, therefore, based on mechanisms to reduce the production and absorption of gut-derived toxins such as decreasing and modifying dietary protein intake, altering the intestinal bacterial flora and bowel cleansing, and on mechanisms designed to modify central neurotransmitter balance either directly by use of dopaminergic agents or benzodiazepine antagonists or indirectly by use of amino-acid mixtures. Some treatment measures, such as use of non-absorbable disaccharides and vegetable protein diets, are known to be efficacious, and are the mainstays of management for all forms of the syndrome. Others are used in more specific circumstances, for example the antibiotic neomycin is effective during acute exacerbations of the syndrome, and the dopamine agonist bromocriptine provides benefit when symptoms are persistent and intractable. Certain treatments such as branched-chain amino acids and the benzodiazepine antagonist, flumazenil, are at present, of unproven value.