L-[1- 13C] phenylalanine breath test reflects phenylalanine hydroxylase activity of the whole liver

Abstract

Object The purpose of this study was to perform L-[1- 13C] phenylalanine breath test (PBT), measure phenylalanine hydroxylase (PAH) activity in liver tissue biopsies from patients, analyze the relationship between PBT results and PAH activity, and determine the time point at which measurements best reflect PAH activity in liver tissue. Methods PBT was performed in 25 patients (10 with normal liver and 15 with liver cirrhosis). After administering 10 mg/kg L-[1- 13C] phenylalanine, 300 ml of expired air was collected over 90 min at 15-min intervals. The rate of hepatic phenylalanine oxidation (% 13C dose h −1) at each time point was calculated from the amount of 13CO 2 in the breath, assuming a CO 2 production rate of 300 mmol m −2 body surface area per hour. Subsequently, we examined the relationship between the results of PBT and PAH activity. Results PAH activity of the whole liver was significantly decreased in hepatic cirrhosis patients ( P < 0.05). The results of PBT % 13C dose h −1 correlated with the PAH activity/liver, with correlation coefficients at 30, 45, and 60 min of more than 0.7, and the maximum correlation was at 30 min ( r = 0.821, P < 0.0001). % 13C cumulative excretion correlated with the PAH activity/liver with correlation coefficients of more than 0.7 after 45 min. The maximum correlation was at 90 min ( r = 0.770, P = 0.001). Conclusion PBT values reflect PAH activity in the whole liver and, in particular, the % dose h −1 at 30 min after oral administration highly correlates with PAH activity, providing an important indicator for monitoring changes in whole liver PAH activity.