Amino acid, ammonia and neurotransmitter concentrations in hepatic encephalopathy: Serial analysis in plasma and cerebrospinal fluid during treatment with an adapted amino acid solution

Abstract

We evaluated changes of advanced liver disease and hepatic encephalopathy on the concentrations of amino acids (AA) and ammonia in plasma and cerebrospinal fluid (CSF) and of the neurotransmitters norepinephrine, dopamine and 5-hydroxytryptamine (5-HT) as well as the 5-hydroxyindole acetic acid (5-HIAA) in CSF before and at the end of a 3-day period of treatment with infusions enriched with branched chain amino acids (BCAA). The subjects studied were 13 patients with alcoholic cirrhosis and hepatic encephalopathy stages 1–3 (n=8) and stage 4 (n=5). The patients in coma stages 1–3 recovered during the treatment (survivors), those in coma stage 4 died before the study period was finished (non-survivors). The data emerging from this study show: 1. Alterations of AA concentrations are much more pronounced in the CSF than in the plasma. In the case of tryptophan the alterations in plasma and CSF were inverse. 2. Before the treatment the CSF-plasma ratios of the concentrations of BCAA and aromatic amino acids (AAA) are increased reflecting an activated transport of both the BCAA and AAA through the blood-brain barrier. 3. High dose BCAA nearly normalized CSF concentrations and CSF-plasma ratios of AAA assuming that the treatment brought about an effective competition of cerebral uptake between BCAA and AAA. 4. The CSF concentrations of ammonia and glutamine decreased significantly during treatment while the plasma concentrations changed only moderately. 5. As to the neurotransmitters, only the concentrations of 5-HT and its metabolite 5-HIAA correlated with the clinical picture and with the concentration of their precursor AA. 6. The normalization or improvement of the CSF concentrations of the AAA, ammonia and glutamine as well as the neurotransmitter 5-HT were accompanied by an improvement of hepatic encephalopathy stages 1–3.