MODEL-DERIVED ASSESSMENT OF UREA APPEARANCE IN RESPONSE TO ALANINE INFUSION - A QUANTITATIVE MEASURE OF LIVER-FUNCTION IN CIRRHOSIS

A three compartment mathematical model was used to analyse the urea re sponse to an alanine infusion in six control subjects, and in 15 patie nts with liver cirrhosis and variable degree of hepatocellular failure . Model-derived coefficients were used to calculate two parameters (Y( max) and T(max)), able to describe the theoretical response of the con version of amino acid derived nitrogen into urea, in response to a uni t impulse in alanine concentration. They correspond to the maximum rat e of conversion of nitrogen from an intermediary pool into urea and to the time delay between the impulse and Y(max), respectively. In cirrh osis, the apparent volume of distribution of infused alanine was small er than in controls, while the conversion of alanine nitrogen into an intermediary pool of nitrogen and finally into urea nitrogen were both reduced. Also Y(max) was reduced by 50% in cirrhosis, whereas T(max) was increased by 50%, and both significantly correlated with galactose elimination capacity (GEC; R2 = 0.706 and R2 = 0.505, respectively) a nd with antipyrine clearance (Ap Cl; R2 = 0.823 and R2 = 0.576 respect ively). Model-derived assessment of urea appearance in response to ala nine infusion is able to quantify the functional liver cell mass, and may prove useful for the study of nitrogen metabolism in cirrhosis, ma inly in relation to encephalopathy.