Alterations of Plasma and Brain Tryptophan in Hepatic Encephalopathy: A Study in Humans and in Experimental Animals

The role of tryptophan in the pathogenesis of hepatic encephalopathy has been investigated both in humans and in experimental animals with a model of chronic liver failure. In a group of 149 patients with liver cirrhosis, it was shown that plasma free tryptophan (the amino acid not bound to albumin) significantly rose when liver function was impaired. This increase was well correlated to the grade of hepatic encephalopathy. The ratio free tryptophan/neutral amino acids showed a comparable behavior. Additionally, free tryptophan markedly decreased in patients recovered from encephalopathy after infusion of an amino acid solution rich in branched chain amino acids. In rats with porto-caval anastomosis brain tryptophan significantly increased to a much larger extent than plasma free tryptophan did. An enhanced activity of the transport system specific for neutral amino acids through the blood brain barrier was confirmed and, at least partly, ascribed to the hyperinsulinemia present after portocaval anastomosis. Serotonin brain levels showed a relatively small increase compared to tryptophan and 5-hydroxyindolacetic acid, implying that tryptophan-hydroxylase could be proportionately inhibited in such experimental model of chronic liver disease.