Subclinical hepatic encephalopathy: role of tryptophan binding to albumin and the competition with indole-3-acetic acid.

Background: The role of tryptophan (TRY) and its metabolites in the pathogenesis of hepatic encephalopathy is conflicting. The aim of the present study is to investigate in posthepatitis cirrhotic patients with encephalopathy the serum levels of TRY and those of its metabolite indole-3-acetic acid, as well as TRY binding curve to serum albumin and the competition with indole-3-acetic acid. The presence of a relationship between encephalopathy severity and circulating free TRY was also investigated.

Methods: Serum TRY and indole-3-acetic acid were analyzed by HPLC; binding of TRY to serum albumin and the competition with indole-3-acetic acid was studied by equilibrium dialysis.

Results: Serum-free TRY was significantly higher in cirrhotic patients (43.33 +/- 14.70 vs 28.87 +/- 8.77 mumol/L, P = 0.02). The binding capacity of albumin was reduced in cirrhotics and further decreased by the addition of indole-3-acetic (K = 6.63 +/- 0.97 x 10(3) mol/L-1, gamma = 1.16 +/- 0.45 x 10(2) mol/L-1 in normal sera vs K = 1.04 +/- 0.20 x 10(3) mol/L-1, gamma = 1.91 +/- 0.92 10(2) mol/L-1 in cirrhotic sera). A multivariate analysis showed that among the psychometric tests the only independent predictor of serum levels of free TRY was the Block Design (R2 = 0.94, B = 0.16 +/- 0.01, beta = 0.97; P < 0.0001).

Conclusions: A high percent ratio of free/total TRY and indoleacetic acid (IAA) was found in cirrhotic patients with hepatic encephalopathy. The concentrations of serum-free IAA and TRY correlated with the degree of subclinical encephalopathy, suggesting a role of these compounds in the development of mental derangement in liver cirrhosis.