C-13-methacetin breath test: Isotope-selective nondispersive infrared spectrometry in comparison to isotope ratio mass spectrometry in volunteers andpatients with liver cirrhosis

The C-13-methacetin breath test (MBT) has been proposed for the noninvasive evaluation of the hepatic mixed function oxidase activity. Up to now, stab le isotope analysis of carbon dioxide of the MBT has been carried out with isotope ratio mass spectrometry (IRMS). The aim of the present study was to test a recently developed isotope-selec tive nondispersive infrared spectrometer (NDIRS) in comparison to IRMS in h ealthy volunteers and patients with liver cirrhosis. Ten healthy volunteers (range 22 to 76 years) and ten patients with histologically proven liver c irrhosis (range 47 to 71 years, Child Pugh score A = 5, B = 3, C = 2) were studied. After an overnight fast each subject received 2 mg/kg BW of C-13-m ethacetin dissolved in 100 ml of tea. Breath samples were obtained before s ubstrate administration and after 5, 10, 15, 20, 30, 10, 50, 60, 100, 120, 150, 180 min. The C-13/C-12-ratio was analyzed in each breath sample both b y NDIRS (IRIS, Wagner Analysen Technik, Worpswede, Germany) and CF-IRMS (AB CA, Europa Scientific, Crewe, UK). Results were expressed as delta over bas eline (DOB [parts per thousand]) and as cumulative percentage doses of C-13 recovered (cPDR [%]) at each time interval. Correlations between IRMS and NDIRS were tested by linear regression correlation. For measuring agreement an Altman-Bland-plot was performed. Applying correlation analysis a linear correlation was found (DOB: y = 1.068 +/- 0.0012.x + 2.088 +/- 0.2126, r = 0.98, p < 0.0001: cPDR: y = 1.118 +/- 0.0109.x + 0.569 +/- 0.172, r = 0.99 , p < 0.0001). For DOB the mean difference (d) was 2.9 parts per thousand a nd the standard deviation (SD) of the difference was 2.7 parts per thousand . The limits of agreement (d +/- SD) were -2.5 parts per thousand and 8.3 p arts per thousand. The comparison of DOB- and cPDR-values by NDIRS and IRMS shows a high linear correlation. However, the distance of the limits of ag reement is wide. Consequently, the validity of the MBT could be influenced which could make MBT by NDIRS unprecise for exact evaluation of hepatocellu lar dysfunction. Further studies are necessary to determine sensitivity and specifity of the MBT with NDIRS in larger study populations.