Whole body leucine, phenylalanine, and tyrosine kinetics in end-stage liver disease before and after hepatic transplantation

The kinetics of leucine, phenylalanine, and tryosine metabolism following orthotopic human liver transplantation in end-stage liver disease in hospitalized patients were evaluated and compared to controls. The investigation was carried out by protein turnover studies using 13C leucine, D5-phenylalanine, and [U- 14C] tyrosine by continuous infusion and employing a stochastic model in 32 patients with end-stage liver disease, 17 of whom went on to receive an hepatic allograft, and 7 controls without significant liver disease who underwent elective abdominal surgery. Mean tyrosine flux in the liver disease group was 3,242 ± 811 (n = 32) v 2,899 ± 688 μmol/h in controls (n = 7) ( P < .001), while the tyrosine oxidation was 328 ± 179 v 422 ± 185 μmol/h( P < .001). Tyrosine clearance in pretransplant pateints was 719 ± 345 (n = 17) v 1,193 ± 568 mL/min( P < .005) in posttransplant patients (n = 17) with virtually no overlap. There was a significant correlation between serum albumin levels and the tyrosine clearance ( r = .60, P < .05), but correlations with other conventional liver function tests were of a low order. Leucine and phenylalanine kinetics in liver disease patients did not show any significant differences from controls. Leucine and tyrosine fluxes in controls did exhibit a significant correlation (r = .70, P < .05), but no correlation was observed in patients with liver disease. These findings indicate that the kinetics of the amino acid tyrosine are substantially altered by end-stage liver disease, with the most profound effect on tyrosine clearance. Tyrosine kinetics reflect amino acid but not whole-body protein metabolism in severe liver disease. Tyrosine clearance rates may serve as a sensitive indicator of hepatic functional reserve and, thus, reflect severity of liver impairment.