EFFECTS OF AN INCREASE IN PROTEIN-INTAKE ON HEPATIC EFFICACY FOR UREA SYNTHESIS IN HEALTHY-SUBJECTS AND IN PATIENTS WITH CIRRHOSIS

The efficacy of urea synthesis as measured by functional hepatic nitrogen clearance (i.e., the relation of urea synthesis rate to blood alpha-amino nitrogen concentration) was studied before and after diet protein supplementation in six healthy subjects and five patients with stable cirrhosis (galactose elimination capacity about 60% of control). Daily protein intake was increased for 14 days by a protein-enriched liquid from (mean +/- S.D.) 1.01 +/- 0.32 g/kg body wt. to 1.62 +/- 0.31 g/kg body wt in the control subjects, and from 0.69 +/- 0.21 g/kg body wt. to 1.50 +/- 0.15 g/kg body wt. in the patients with cirrhosis. This increased the hepatic nitrogen clearance from 27 +/- 10 l/h to 39 +/- 15 l/h in the control subjects (p < 0.05) and from 15 +/- 6 l/h to 21 +/- 7 l/h in the cirrhosis patients (p < 0.05). There was no effect on the galactose elimination capacity in any group. Compared to the control subjects, the response in hepatic nitrogen clearance relative to the increase in protein intake was reduced by 60% in the patients. Basal glucagon was 75% higher in the patients and increased by 50% during high protein intake (p < 0.05), but did not parallel the increase in hepatic nitrogen clearance, and it did not change in the control subjects. The study shows that an increase in protein intake selectively increases liver function with regard to disposal of amino nitrogen; the mechanism is qualitatively intact but quantitatively deficient in patients with cirrhosis of the liver, and does not seem to depend on glucagon.