Interpretation of non-invasive breath tests using 13C-labeled substrates - a preliminary report with 13C-methacetin

European Journal of Medical Research

M Stockmann²  P Neuhaus²  M Malinowski²  HG Holzhütter¹  S Bauer³  P Taheri²  JF Lock² 

[1] Institute of Biochemistry, Charité - Universitätsmedizin Berlin, Germany;Department of General, Visceral and Transplantation Surgery, Charité - Universitätsmedizin Berlin, Germany;Institute of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin Berlin, Germany

关键词: LiMAx test;    cytochrome P450 1A2;    methacetin;    ¹³C-breath test;    liver function test;    liver function;   

Others  :  1093406
DOI  :  10.1186/2047-783X-14-12-547

 received in 2009-09-07, accepted in 2009-10-01,  发布年份 2009

【 摘 要 】

Non-invasive breath tests can serve as valuable diagnostic tools in medicine as they can determine particular enzymatic and metabolic functions in vivo. However, methodological pitfalls have limited the actual clinical application of those tests till today. A major challenge of non-invasive breath tests has remained the provision of individually reliable test results. To overcome these limitations, a better understanding of breath kinetics during non-invasive breaths tests is essential. This analysis compares the breath recovery of a ¹³C-methacetin breath test with the actual serum kinetics of the substrate. It is shown, that breath and serum kinetics of the same test are significantly different over a period of 60 minutes. The recovery of the tracer ¹³CO₂ in breath seems to be significantly delayed due to intermediate storage in the bicarbonate pool. This has to be taken into account for the application of non-invasive breath test protocols. Otherwise, breath tests might display bicarbonate kinetics despite the metabolic capacity of the particular target enzyme.

【 授权许可】

   
2009 I. Holzapfel Publishers

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Klein PD: Clinical applications of 13CO2 measurements. Fed Proc 1982, 41(10):2698-701.
• [2]Klein PD: 13C breath tests: visions and realities. J Nutr 2001, 131(5):1637S-42S.
• [3]Matsumoto K, Suehiro M, Iio M, Kawabe T, Shiratori Y, Okano K, Sugimoto T: [13C]methacetin breath test for evaluation of liver damage. Dig Dis Sci 1987, 32(4):344-8.
• [4]Adamek RJ, Goetze O, Boedeker C, Pfaffenbach B, Luy paerts A, Geypens B: 13C-methacetin breath test: isotope-selective nondispersive infrared spectrometry in comparison to isotope ratio mass spectrometry in volunteers and patients with liver cirrhosis. Z Gastroenterol 1999, 37(12):1139-43.
• [5]Ilan Y: Review article: the assessment of liver function using breath tests. Aliment Pharmacol Ther 2007, 26(10):1293-302.
• [6]Schneider A, Caspary WF, Saich R, Dietrich CF, Sarrazin C, Kuker W, Braden B: 13C-methacetin breath test shortened: 2-point-measurements after 15 minutes reliably indicate the presence of liver cirrhosis. J Clin Gastroenterol 2007, 41(1):33-7.
• [7]Stockmann M, Lock JF, Riecke B, Heyne C, Martus P, Fricke M, Lehmann S, Niehues SM, Schwabe M, Lemke A-J, Neuhaus P: Prediction of Postoperative Outcome after Hepatectomy With a New Bedside Test for Maximal Liver Function Capacity. Ann Surg 2009, 250(1):119-25.
• [8]Irving CS, Wong WW, Shulman RJ, Smith EO, Klein PD: [13C]bicarbonate kinetics in humans: intra- vs. interindividual variations. Am J Physiol 1983, 245(2):R190-202.
• [9]Irving CS, Schoeller DA, Nakamura KI, Baker AL, Klein PD: The aminopyrine breath test as a measure of liver function. A quantitative description of its metabolic basis in normal subjects. J Lab Clin Med 1982, 100(3):356-73.
• [10]Lane EA, Parashos I: Drug pharmacokinetics and the carbon dioxide breath test. J Pharmacokinet Biopharm 1986, 14(1):29-49.
• [11]Schoeller DA, Brown C, Nakamura K, Nakagawa A, Mazzeo RS, Brooks GA, Budinger TF: Influence of metabolic fuel on the 13C/12C ratio of breath CO2. Biomed Mass Spectrom 1984, 11(11):557-61.
• [12]Schoeller DA, Schneider JF, Solomons NW, Watkins JB, Klein PD: Clinical diagnosis with the stable isotope 13C in CO2 breath tests: methodology and fundamental considerations. J Lab Clin Med 1977, 90(3):412-21.
• [13]Barstow TJ, Cooper DM, Sobel EM, Landaw EM, Epstein S: Influence of increased metabolic rate on [13C]bicarbonate washout kinetics. Am J Physiol 1990, 259(1 Pt 2):R163-71.
• [14]Meineke I, De Mey C, Eggers R, Bauer FE: Evaluation of the 13CO2 kinetics in humans after oral application of sodium bicarbonate as a model for breath testing. Eur J Clin Invest 1993, 23(2):91-6.
• [15]Roecker K, Landaw E, Striegel H, Mayer F, Dickhuth HH: First-pass effect of an intravenous bolus of [13C]bicarbonate displayed breath-by-breath. J Appl Physiol 2001, 90(6):2181-7.
• [16]Braden B, Faust D, Sarrazin U, Zeuzem S, Dietrich CF, Caspary WF, Sarrazin C: 13C-methacetin breath test as liver function test in patients with chronic hepatitis C virus infection. Aliment Pharmacol Ther 2005, 21(2):179-85.
• [17]Kasicka-Jonderko A, Jonderko K, Chabior E, Blonska-Fajfrowska B: Exact profiles of (13)CO(2) recovery in breath air after per oral administration of [(13)C]metha cetin in two groups of different ages. Isotopes Environ Health Stud 2008, 44(3):295-303.
• [18]Lalazar G, Adar T, Ilan Y: Point-of-care continuous (13)C-methacetin breath test improves decision making in acute liver disease: results of a pilot clinical trial. World J Gastroenterol 2009, 15(8):966-72.
• [19]Armuzzi A, Candelli M, Zocco MA, Andreoli A, De Lorenzo A, Nista EC, Miele L, Cremonini F, Cazzato IA, Grieco A, Gasbarrini G, Gasbarrini A: Review article: breath testing for human liver function assessment. Aliment Pharmacol Ther 2002, 16(12):1977-96.