Validity of the 13C–Caffeine Breath Test As A Noninvasive, Quantitative Test of Liver Function

Abstract

The properties of caffeine render it an ideal substrate for a quantitative test of liver function. The aim of this study was to determine whether the caffeine breath test (CBT) using orally administered 13 C-caffeine correlates reliably with plasma caffeine clearance and reflects varying degrees of liver dysfunction. The CBT was performed in 25 healthy controls; 20 subjects with noncirrhotic, chronic hepatitis B or C; and 20 subjects with cirrhosis. Plasma caffeine clearance was assayed simultaneously with the CBT in a cohort of these subjects. Over a broad range of caffeine clearances, the CBT exhibited a highly significant correlation with plasma clearance (r ‫؍‬ 0.85, P < .001). Cirrhotic patients were characterized by significantly reduced CBT values (1.15 ؎ 0.75 ‚‰ mg ؊1 ) compared with controls (2.23 ؎ 0.76; P ‫؍‬ .001) and hepatitic patients (1.83 ؎ 1.05; P ‫؍‬ .04). There was a significant inverse relationship between the CBT and Child-Pugh score (r ‫؍‬ ؊.74, P ‫؍‬ .002). The intraclass correlation coefficient between repeated CBTs in 20 subjects with normal and cirrhotic livers was 0.89. Although smoking was associated with an 86% to 141% increase in CBT in all groups, the CBT was able to distinguish control, hepatitic, and cirrhotic smokers (5.36 ؎ 0.82, 3.63 ؎ 1.21, and 2.14 ؎ 1.14, respectively, P ‫؍‬ .001). Multivariate analysis revealed that only smoking (P < .001) and disease state (P ‫؍‬ .001) were significant predictors of the CBT. In conclusion, the 13 C-CBT represents a valid indicator of plasma caffeine clearance and correlates reproducibly with hepatic dysfunction. (HEPATOLOGY 2003;38:1227-1236

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

“…The correlation between CYP2D6 phenotype, determined by the [ 13 C]-dextromethorphan breath test, and serum endoxifen levels was comparable with the correlation between the latter and sequence-based CYP2D6 activity prediction [131]. For the CYP1A2 substrate [ 13 C]-caffeine, Park et al observed a significant correlation between 1 h single DOB 13 CO 2 / 12 CO 2 ratios and plasma [ 13 C]-caffeine clearance [132]. These results were in agreement with previous studies, in which excellent correlations between caffeine breath test results and caffeine clearance were found [133][134][135][136].…”

Critical appraisal of 13C breath tests for microsomal liver function: aminopyrine revisited

“…13 C-caffeine breath test 13 C-labelled caffeine, (3-methyl-13 C) caffeine, is metabolized mainly in the liver through N-demethylation by the cytochrome P450 isoenzyme CYP1A2, yielding three major metabolites: theophylline, paraxanthine and theobromine (1,16,25), but only the conversion into paraxanthine results in 13 CO 2 . Caffeine labelled with 13 C in all three (1, 3 and 7) methyl groups or specifically in the 1-, 3-or 7-methyl groups can also be used.…”

“…A 'well-designed' study by Park et al (25) showed that the 13 C-labelled caffeine breath test was significantly correlated with the plasma caffeine clearance, and with several liver tests (e.g. serum albumin).…”

Funktionsdiagnostik vor Leberresektion - teuer und ohne klinische Relevanz?

“…Schließlich wurde bei Kindern eine größere Sensitivität des Tests bei akutem Leberversagen im Vergleich mit den King's College Kriterien propagiert [36]. Originalarbeiten und Übersichten in allen Studien belegt werden [50,55]. Auch beeinflusst Rauchen die Koffein-Clearance erheblich [50].…”

“…Originalarbeiten und Übersichten in allen Studien belegt werden [50,55]. Auch beeinflusst Rauchen die Koffein-Clearance erheblich [50]. Aufgrund ihrer problemlosen Verfügbarkeit und fehlenden Toxizität stellt die Koffein-Clearance methodisch eine interessante Option dar, die jedoch weiterer Optimierung insbesondere hinsichtlich einer präoperativen Abschätzung der Funktionsreserve der Leber benötigt.…”