Skip to main content
Erschienen in: Digestive Diseases and Sciences 12/2014

01.12.2014 | Original Article

Enzymatic Liver Function Capacity Correlates with Disease Severity of Patients with Liver Cirrhosis: A Study with the LiMAx Test

verfasst von: Maciej Malinowski, Maximilian Jara, Katja Lüttgert, James Orr, Johan Friso Lock, Eckart Schott, Martin Stockmann

Erschienen in: Digestive Diseases and Sciences | Ausgabe 12/2014

Einloggen, um Zugang zu erhalten

Abstract

Background

Assessment and quantification of actual liver function is crucial in patients with chronic liver disease to monitor disease progression and predict individual prognosis. Mathematical models, such as model for end-stage liver disease, are used for risk stratification of patients with chronic liver disease but do not include parameters that reflect the actual functional state of the liver.

Aim

We aimed to evaluate the potential of a 13C-based liver function test as a stratification tool by comparison with other liver function tests and clinical parameters in a large sample of healthy controls and cirrhotic patients.

Methods

We applied maximum liver function capacity (LiMAx) to evaluate actual liver function in 347 patients with cirrhosis and in 86 controls.

Results

LiMAx showed strong negative correlation with Child-Pugh Score (r = −0.707; p < 0.001), MELD (r = −0.686; p < 0.001) and liver function tests. LiMAx was lower in patients with liver cirrhosis compared to healthy controls [99 (57–160) µg/kg/h vs. 412 (365–479) µg/kg/h, p < 0.001] and differed among Child-Pugh classes [a: 181 (144–227) µg/kg/h, b: 96 (62–132) µg/kg/h and c: 52 (37–81) µg/kg/h; p < 0.001]. When stratified patients according to disease severity, LiMAx results were not different between cirrhotic patients and cirrhotic patients with transjugular intrahepatic portosystemic shunt.

Conclusions

LiMAx appears to provide reliable information on remnant enzymatic liver function in chronic liver disease and allows graduation of disease severity.
Literatur
1.
Zurück zum Zitat Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology. 1994;19:1513–1520.PubMedCrossRef Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology. 1994;19:1513–1520.PubMedCrossRef
2.
Zurück zum Zitat Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60:646–649.PubMedCrossRef Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60:646–649.PubMedCrossRef
3.
Zurück zum Zitat Kamath PS, Kim WR. The Model for End-stage Liver Disease (MELD). Hepatology. 2007;45:797–805.PubMedCrossRef Kamath PS, Kim WR. The Model for End-stage Liver Disease (MELD). Hepatology. 2007;45:797–805.PubMedCrossRef
4.
Zurück zum Zitat Kim WR, Biggins SW, Kremers WK, et al. Hyponatremia and mortality among patients on the liver-transplant waiting list. N Engl J Med. 2008;359:1018–1026.PubMedCrossRef Kim WR, Biggins SW, Kremers WK, et al. Hyponatremia and mortality among patients on the liver-transplant waiting list. N Engl J Med. 2008;359:1018–1026.PubMedCrossRef
5.
Zurück zum Zitat Wai CT, Greenson JK, Fontana RJ, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38:518–526.PubMedCrossRef Wai CT, Greenson JK, Fontana RJ, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38:518–526.PubMedCrossRef
6.
Zurück zum Zitat Oellerich M, Burdelski M, Lautz HU, Schulz M, Schmidt FW, Herrmann H. Lidocaine metabolite formation as a measure of liver function in patients with cirrhosis. Ther Drug Monit. 1990;12:219–226.PubMedCrossRef Oellerich M, Burdelski M, Lautz HU, Schulz M, Schmidt FW, Herrmann H. Lidocaine metabolite formation as a measure of liver function in patients with cirrhosis. Ther Drug Monit. 1990;12:219–226.PubMedCrossRef
7.
Zurück zum Zitat Mion F, Queneau PE, Rousseau M, Brazier JL, Paliard P, Minaire Y. Aminopyrine breath test: development of a 13C-breath test for quantitative assessment of liver function in humans. Hepatogastroenterology.. 1995;42:931–938.PubMed Mion F, Queneau PE, Rousseau M, Brazier JL, Paliard P, Minaire Y. Aminopyrine breath test: development of a 13C-breath test for quantitative assessment of liver function in humans. Hepatogastroenterology.. 1995;42:931–938.PubMed
8.
Zurück zum Zitat Figg WD, Dukes GE, Lesesne HR, et al. Comparison of quantitative methods to assess hepatic function: Pugh’s classification, indocyanine green, antipyrine, and dextromethorphan. Pharmacotherapy.. 1995;15:693–700.PubMed Figg WD, Dukes GE, Lesesne HR, et al. Comparison of quantitative methods to assess hepatic function: Pugh’s classification, indocyanine green, antipyrine, and dextromethorphan. Pharmacotherapy.. 1995;15:693–700.PubMed
9.
Zurück zum Zitat Baruque S, Razquin M, Jimenez I, Vazquez A, Gisbert JP, Pajares JM. 13C-phenylalanine and 13C-methacetin breath test to evaluate functional capacity of hepatocyte in chronic liver disease. Dig Liver Dis. 2000;32:226–232.CrossRef Baruque S, Razquin M, Jimenez I, Vazquez A, Gisbert JP, Pajares JM. 13C-phenylalanine and 13C-methacetin breath test to evaluate functional capacity of hepatocyte in chronic liver disease. Dig Liver Dis. 2000;32:226–232.CrossRef
10.
Zurück zum Zitat Herold C, Heinz R, Radespiel-Troger M, Schneider HT, Schuppan D, Hahn EG. Quantitative testing of liver function in patients with cirrhosis due to chronic hepatitis C to assess disease severity. Liver.. 2001;21:26–30.PubMedCrossRef Herold C, Heinz R, Radespiel-Troger M, Schneider HT, Schuppan D, Hahn EG. Quantitative testing of liver function in patients with cirrhosis due to chronic hepatitis C to assess disease severity. Liver.. 2001;21:26–30.PubMedCrossRef
11.
Zurück zum Zitat Parra D, Gonzalez A, Garcia-Villarreal L, Martinez JA. Methodological characterization of the 2-keto [1-13C]isocaproate breath test to measure in vivo human mitochondrial function: application in alcoholic liver disease assessment. Alcohol Clin Exp Res.. 2003;27:1293–1298.PubMedCrossRef Parra D, Gonzalez A, Garcia-Villarreal L, Martinez JA. Methodological characterization of the 2-keto [1-13C]isocaproate breath test to measure in vivo human mitochondrial function: application in alcoholic liver disease assessment. Alcohol Clin Exp Res.. 2003;27:1293–1298.PubMedCrossRef
12.
Zurück zum Zitat Park GJ, Katelaris PH, Jones DB, Seow F, Le Couteur DG, Ngu MC. Validity of the 13C-caffeine breath test as a noninvasive, quantitative test of liver function. Hepatology. 2003;38:1227–1236.PubMedCrossRef Park GJ, Katelaris PH, Jones DB, Seow F, Le Couteur DG, Ngu MC. Validity of the 13C-caffeine breath test as a noninvasive, quantitative test of liver function. Hepatology. 2003;38:1227–1236.PubMedCrossRef
13.
Zurück zum Zitat Mukherjee S, Rogers MA, Buniak B. Comparison of indocyanine green clearance with Child’s-Pugh score and hepatic histology: a multivariate analysis. Hepatogastroenterology. 2006;53:120–123.PubMed Mukherjee S, Rogers MA, Buniak B. Comparison of indocyanine green clearance with Child’s-Pugh score and hepatic histology: a multivariate analysis. Hepatogastroenterology. 2006;53:120–123.PubMed
14.
Zurück zum Zitat Forestier J, Dumortier J, Guillaud O. Noninvasive diagnosis and prognosis of liver cirrhosis: a comparison of biological scores, elastometry, and metabolic liver function tests. Eur J Gastroenterol Hepatol. 2010;22:532–540.PubMedCrossRef Forestier J, Dumortier J, Guillaud O. Noninvasive diagnosis and prognosis of liver cirrhosis: a comparison of biological scores, elastometry, and metabolic liver function tests. Eur J Gastroenterol Hepatol. 2010;22:532–540.PubMedCrossRef
15.
Zurück zum Zitat Afolabi P, Wright M, Wootton SA, Jackson AA. 13C-aminopyrine demethylation is decreased in cirrhotic patients with normal biochemical markers. Isotopes Environ Health Stud. 2013;49:346–356.PubMedCrossRef Afolabi P, Wright M, Wootton SA, Jackson AA. 13C-aminopyrine demethylation is decreased in cirrhotic patients with normal biochemical markers. Isotopes Environ Health Stud. 2013;49:346–356.PubMedCrossRef
16.
Zurück zum Zitat Stockmann M, Lock JF, Riecke B, et al. Prediction of postoperative outcome after hepatectomy with a new bedside test for maximal liver function capacity. Ann Surg. 2009;250:119–125.PubMedCrossRef Stockmann M, Lock JF, Riecke B, et al. Prediction of postoperative outcome after hepatectomy with a new bedside test for maximal liver function capacity. Ann Surg. 2009;250:119–125.PubMedCrossRef
17.
Zurück zum Zitat Stockmann M, Lock JF, Malinowski M, Niehues SM, Seehofer D, Neuhaus P. The LiMAx test: a new liver function test for predicting postoperative outcome in liver surgery. HPB (Oxford). 2010;12:139–146.CrossRef Stockmann M, Lock JF, Malinowski M, Niehues SM, Seehofer D, Neuhaus P. The LiMAx test: a new liver function test for predicting postoperative outcome in liver surgery. HPB (Oxford). 2010;12:139–146.CrossRef
18.
Zurück zum Zitat Palmer CN, Coates PJ, Davies SE, Shephard EA, Phillips IR. Localization of cytochrome P-450 gene expression in normal and diseased human liver by in situ hybridization of wax-embedded archival material. Hepatology.. 1992;16:682–687.PubMedCrossRef Palmer CN, Coates PJ, Davies SE, Shephard EA, Phillips IR. Localization of cytochrome P-450 gene expression in normal and diseased human liver by in situ hybridization of wax-embedded archival material. Hepatology.. 1992;16:682–687.PubMedCrossRef
19.
Zurück zum Zitat Pfaffenbach B, Gotze O, Szymanski C, Hagemann D, Adamek RJ. The 13C-methacetin breath test for quantitative noninvasive liver function analysis with an isotope-specific nondispersive infrared spectrometer in liver cirrhosis. Dtsch Med Wochenschr.. 1998;123:1467–1471.PubMedCrossRef Pfaffenbach B, Gotze O, Szymanski C, Hagemann D, Adamek RJ. The 13C-methacetin breath test for quantitative noninvasive liver function analysis with an isotope-specific nondispersive infrared spectrometer in liver cirrhosis. Dtsch Med Wochenschr.. 1998;123:1467–1471.PubMedCrossRef
20.
Zurück zum Zitat Lock JF, Malinowski M, Seehofer D, et al. Function and volume recovery after partial hepatectomy: influence of preoperative liver function, residual liver volume, and obesity. Langenbecks Arch Surg. 2012;397:1297–1304.PubMedCrossRef Lock JF, Malinowski M, Seehofer D, et al. Function and volume recovery after partial hepatectomy: influence of preoperative liver function, residual liver volume, and obesity. Langenbecks Arch Surg. 2012;397:1297–1304.PubMedCrossRef
21.
Zurück zum Zitat Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001;33:464–470.PubMedCrossRef Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001;33:464–470.PubMedCrossRef
22.
Zurück zum Zitat Riordan SM, Williams R. Treatment of hepatic encephalopathy. N Engl J Med. 1997;337:473–479.PubMedCrossRef Riordan SM, Williams R. Treatment of hepatic encephalopathy. N Engl J Med. 1997;337:473–479.PubMedCrossRef
24.
Zurück zum Zitat Stockmann M, Lock JF, Malinowski M, et al. How to define initial poor graft function after liver transplantation?—A new functional definition by the LiMAx test. Transpl Int. 2010;23:1023–1032.PubMedCrossRef Stockmann M, Lock JF, Malinowski M, et al. How to define initial poor graft function after liver transplantation?—A new functional definition by the LiMAx test. Transpl Int. 2010;23:1023–1032.PubMedCrossRef
25.
Zurück zum Zitat Lock JF, Schwabauer E, Martus P, et al. Early diagnosis of primary nonfunction and indication for reoperation after liver transplantation. Liver Transpl. 2010;16:172–180.PubMedCrossRef Lock JF, Schwabauer E, Martus P, et al. Early diagnosis of primary nonfunction and indication for reoperation after liver transplantation. Liver Transpl. 2010;16:172–180.PubMedCrossRef
26.
Zurück zum Zitat Lock JF, Kotobi AN, Malinowski M, et al. Predicting the prognosis in acute liver failure: results from a retrospective pilot study using the LiMAx test. Ann Hepatol. 2013;12:556–562.PubMed Lock JF, Kotobi AN, Malinowski M, et al. Predicting the prognosis in acute liver failure: results from a retrospective pilot study using the LiMAx test. Ann Hepatol. 2013;12:556–562.PubMed
27.
Zurück zum Zitat Baker AL, Krager PS, Kotake AN, Schoeller DA. The aminopyrine breath test does not correlate with histologic disease severity in patients with cholestasis. Hepatology. 1987;7:464–467.PubMedCrossRef Baker AL, Krager PS, Kotake AN, Schoeller DA. The aminopyrine breath test does not correlate with histologic disease severity in patients with cholestasis. Hepatology. 1987;7:464–467.PubMedCrossRef
28.
29.
Zurück zum Zitat Weismuller TJ, Wedemeyer J, Kubicka S, Strassburg CP, Manns MP. The challenges in primary sclerosing cholangitis–aetiopathogenesis, autoimmunity, management and malignancy. J Hepatol. 2008;48(Suppl 1):S38–S57.PubMedCrossRef Weismuller TJ, Wedemeyer J, Kubicka S, Strassburg CP, Manns MP. The challenges in primary sclerosing cholangitis–aetiopathogenesis, autoimmunity, management and malignancy. J Hepatol. 2008;48(Suppl 1):S38–S57.PubMedCrossRef
30.
Zurück zum Zitat Giannini EG, Savarino V. Relationship between 13C-aminopyrine breath test and the MELD score and its long-term prognostic use in patients with cirrhosis. Dig Dis Sci. 2013;58:3024–3028.PubMedCrossRef Giannini EG, Savarino V. Relationship between 13C-aminopyrine breath test and the MELD score and its long-term prognostic use in patients with cirrhosis. Dig Dis Sci. 2013;58:3024–3028.PubMedCrossRef
31.
Zurück zum Zitat Schneider JF, Baker AL, Haines NW, Hatfield G, Boyer JL. Aminopyrine N-demethylation: a prognostic test of liver function in patients with alcoholic liver disease. Gastroenterology. 1980;79:1145–1150.PubMed Schneider JF, Baker AL, Haines NW, Hatfield G, Boyer JL. Aminopyrine N-demethylation: a prognostic test of liver function in patients with alcoholic liver disease. Gastroenterology. 1980;79:1145–1150.PubMed
32.
Zurück zum Zitat Merkel C, Gatta A, Zoli M, et al. Prognostic value of galactose elimination capacity, aminopyrine breath test, and ICG clearance in patients with cirrhosis. Comparison with the Pugh score. Dig Dis Sci. 1991;36:1197–1203.PubMedCrossRef Merkel C, Gatta A, Zoli M, et al. Prognostic value of galactose elimination capacity, aminopyrine breath test, and ICG clearance in patients with cirrhosis. Comparison with the Pugh score. Dig Dis Sci. 1991;36:1197–1203.PubMedCrossRef
33.
Zurück zum Zitat Degre D, Bourgeois N, Boon N, et al. Aminopyrine breath test compared to the MELD and Child-Pugh scores for predicting mortality among cirrhotic patients awaiting liver transplantation. Transpl Int. 2004;17:31–38.PubMedCrossRef Degre D, Bourgeois N, Boon N, et al. Aminopyrine breath test compared to the MELD and Child-Pugh scores for predicting mortality among cirrhotic patients awaiting liver transplantation. Transpl Int. 2004;17:31–38.PubMedCrossRef
34.
Zurück zum Zitat Fabbri A, Bianchi G, Motta E, Brizi M, Zoli M, Marchesini G. The galactose elimination capacity test: a study of the technique based on the analysis of 868 measurements. Am J Gastroenterol. 1996;91:991–996.PubMed Fabbri A, Bianchi G, Motta E, Brizi M, Zoli M, Marchesini G. The galactose elimination capacity test: a study of the technique based on the analysis of 868 measurements. Am J Gastroenterol. 1996;91:991–996.PubMed
35.
Zurück zum Zitat Stremmel W, Wojdat R, Groteguth R, et al. [Liver function tests in a clinical comparison]. Z Gastroenterol. 1992;30:784–790.PubMed Stremmel W, Wojdat R, Groteguth R, et al. [Liver function tests in a clinical comparison]. Z Gastroenterol. 1992;30:784–790.PubMed
36.
Zurück zum Zitat Stockmann M, Malinowski M, Lock JF, Seehofer D, Neuhaus P. Factors influencing the indocyanine green (ICG) test: additional impact of acute cholestasis. Hepatogastroenterology.. 2009;56:734–738.PubMed Stockmann M, Malinowski M, Lock JF, Seehofer D, Neuhaus P. Factors influencing the indocyanine green (ICG) test: additional impact of acute cholestasis. Hepatogastroenterology.. 2009;56:734–738.PubMed
Metadaten
Titel
Enzymatic Liver Function Capacity Correlates with Disease Severity of Patients with Liver Cirrhosis: A Study with the LiMAx Test
verfasst von
Maciej Malinowski
Maximilian Jara
Katja Lüttgert
James Orr
Johan Friso Lock
Eckart Schott
Martin Stockmann
Publikationsdatum
01.12.2014
Verlag
Springer US
Erschienen in
Digestive Diseases and Sciences / Ausgabe 12/2014
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-014-3250-z

Weitere Artikel der Ausgabe 12/2014

Digestive Diseases and Sciences 12/2014 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.