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Published in: CardioVascular and Interventional Radiology 12/2019

01-12-2019 | Clinical Investigation

Monitoring Liver Function of Patients Undergoing Transarterial Chemoembolization (TACE) by a 13C Breath Test (LiMAx)

Authors: Emona S. Barzakova, Maximilian Schulze-Hagen, Markus Zimmermann, Georg Lurje, Jan Bednarsch, Federico Pedersoli, Peter Isfort, Christiane Kuhl, Philipp Bruners

Published in: CardioVascular and Interventional Radiology | Issue 12/2019

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Abstract

Purpose

Transarterial chemoembolization (TACE) is associated with the risk of deteriorating liver function, especially in patients with preexisting liver damage. Current liver function tests may fail to accurately predict the functional liver reserve. Aim of this study was to investigate whether changes of liver function caused by TACE are associated with detectable changes of LiMAx values.

Methods and Materials

Forty patients with primary or secondary liver cancer underwent TACE and LiMAx test on the day before, the day after, and 4 weeks after TACE. LiMAx results were evaluated, referenced to liver volume (CT/MR volumetry), correlated with the respective TACE volume (subsegmental vs. segmental vs. lobar), established liver function tests, and Child–Pugh and ALBI scores.

Results

The individual LiMAx values were significantly reduced by 10% (p = 0.01) on the day after TACE and fully recovered to baseline 1 month after treatment. Similar changes were observed regarding levels of bilirubin, transaminases, albumin, INR, and creatinine. LiMAx did not correlate significantly with the treated liver volume, but did correlate with the baseline liver volume (< 1200 ml vs. > 1200 ml; p < 0.01). No significant changes were observed in the Child–Pugh score or ALBI score.

Conclusion

LiMAx is capable of detecting changes in liver function, even modulations caused by superselective TACE procedures. Accordingly, it could be used as a tool for patient selection and monitoring of transarterial therapy. In comparison, Child–Pugh and ALBI scores did not reflect any of these changes. Some biochemical parameters also changed significantly after TACE, but they tend to be less specific in providing sufficient information on actual cellular dysfunction.
Literature
1.
go back to reference Chan AO, Yuen MF, Hui CK, Tso WK, Lai CL. A prospective study regarding the complications of transcatheter intraarterial lipiodol chemoembolization in patients with hepatocellular carcinoma. Cancer. 2002;94(6):1747–52.PubMedCrossRef Chan AO, Yuen MF, Hui CK, Tso WK, Lai CL. A prospective study regarding the complications of transcatheter intraarterial lipiodol chemoembolization in patients with hepatocellular carcinoma. Cancer. 2002;94(6):1747–52.PubMedCrossRef
2.
go back to reference Takayasu K, Arii S, Ikai I, Omata M, Okita K, Ichida T, Matsuyama Y, Nakanuma Y, Kojiro M, Makuuchi M, Yamaoka Y, Liver Cancer Study Group of Japan. Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterology. 2006;131(2):461–9PubMedCrossRef Takayasu K, Arii S, Ikai I, Omata M, Okita K, Ichida T, Matsuyama Y, Nakanuma Y, Kojiro M, Makuuchi M, Yamaoka Y, Liver Cancer Study Group of Japan. Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterology. 2006;131(2):461–9PubMedCrossRef
3.
go back to reference Min YW, Kim J, Kim S, Sung YK, Lee JH, Gwak GY, Paik YH, Choi MS, Koh KC, Paik SW, Yoo BC, Lee JH. Risk factors and a predictive model for acute hepatic failure after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. Liver Int. 2013;33(2):197–202.PubMedCrossRef Min YW, Kim J, Kim S, Sung YK, Lee JH, Gwak GY, Paik YH, Choi MS, Koh KC, Paik SW, Yoo BC, Lee JH. Risk factors and a predictive model for acute hepatic failure after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. Liver Int. 2013;33(2):197–202.PubMedCrossRef
4.
go back to reference Huang YS, Chiang JH, Wu JC, Chang FY, Lee SD. Risk of hepatic failure after transcatheter arterial chemoembolization for hepatocellular carcinoma: predictive value of the monoethylglycinexylidide test. Am J Gastroenterol. 2002;97(5):1223–7.PubMedCrossRef Huang YS, Chiang JH, Wu JC, Chang FY, Lee SD. Risk of hepatic failure after transcatheter arterial chemoembolization for hepatocellular carcinoma: predictive value of the monoethylglycinexylidide test. Am J Gastroenterol. 2002;97(5):1223–7.PubMedCrossRef
5.
go back to reference Shalimar, Subrat Acharya K, William Lee M. Worldwide differences in acute liver failure. Critical care in acute liver failure. London: Future Medicine Ltd; 2013:32–46.CrossRef Shalimar, Subrat Acharya K, William Lee M. Worldwide differences in acute liver failure. Critical care in acute liver failure. London: Future Medicine Ltd; 2013:32–46.CrossRef
6.
go back to reference Gehl J, Omary RA. Transarterial chemoembolization complicated by deteriorating hepatic function. Semin Interv Radiol. 2011;28(2):198–201.CrossRef Gehl J, Omary RA. Transarterial chemoembolization complicated by deteriorating hepatic function. Semin Interv Radiol. 2011;28(2):198–201.CrossRef
7.
go back to reference Kothary N, Weintraub JL, Susman J, Rundback JH. Transarterial chemoembolization for primary hepatocellular carcinoma in patients at high risk. J Vasc Interv Radiol. 2007;18(12):1517–26.PubMedCrossRef Kothary N, Weintraub JL, Susman J, Rundback JH. Transarterial chemoembolization for primary hepatocellular carcinoma in patients at high risk. J Vasc Interv Radiol. 2007;18(12):1517–26.PubMedCrossRef
8.
go back to reference Georgiades CS, Liapi E, Frangakis C, Park JU, Kim HW, Hong K, Geschwind JF. Prognostic accuracy of 12 liver staging systems in patients with unresectable hepatocellular carcinoma treated with transarterial chemoembolization. J Vasc Interv Radiol. 2006;17(10):1619–24.PubMedCrossRef Georgiades CS, Liapi E, Frangakis C, Park JU, Kim HW, Hong K, Geschwind JF. Prognostic accuracy of 12 liver staging systems in patients with unresectable hepatocellular carcinoma treated with transarterial chemoembolization. J Vasc Interv Radiol. 2006;17(10):1619–24.PubMedCrossRef
9.
go back to reference Chung JW, Park JH, Han JK, Choi BI, Han MC, Lee HS, Kim CY. Hepatic tumors: predisposing factors for complications of transcatheter oily chemoembolization. Radiology. 1996;198(1):33–40.PubMedCrossRef Chung JW, Park JH, Han JK, Choi BI, Han MC, Lee HS, Kim CY. Hepatic tumors: predisposing factors for complications of transcatheter oily chemoembolization. Radiology. 1996;198(1):33–40.PubMedCrossRef
10.
go back to reference Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–2.PubMedCrossRef Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–2.PubMedCrossRef
11.
go back to reference Na SK, Yim SY, Suh SJ, Jung YK, Kim JH, Seo YS, Yim HJ, Yeon JE, Byun KS, Um SH. ALBI versus Child-Pugh grading systems for liver function in patients with hepatocellular carcinoma. J Surg Oncol. 2018;117(5):912–21.PubMedCrossRef Na SK, Yim SY, Suh SJ, Jung YK, Kim JH, Seo YS, Yim HJ, Yeon JE, Byun KS, Um SH. ALBI versus Child-Pugh grading systems for liver function in patients with hepatocellular carcinoma. J Surg Oncol. 2018;117(5):912–21.PubMedCrossRef
12.
go back to reference Su TS, Yang HM, Zhou Y, Huang Y, Liang P, Cheng T, Chen L, Li LQ, Liang SX. Albumin-bilirubin (ALBI) versus Child-Turcotte-Pugh (CTP) in prognosis of HCC after stereotactic body radiation therapy. Radiat Oncol. 2019;14(1):50.PubMedPubMedCentralCrossRef Su TS, Yang HM, Zhou Y, Huang Y, Liang P, Cheng T, Chen L, Li LQ, Liang SX. Albumin-bilirubin (ALBI) versus Child-Turcotte-Pugh (CTP) in prognosis of HCC after stereotactic body radiation therapy. Radiat Oncol. 2019;14(1):50.PubMedPubMedCentralCrossRef
13.
go back to reference Gui B, Weiner AA, Nosher J, et al. Assessment of the albumin-bilirubin (ALBI) grade as a prognostic indicator for hepatocellular carcinoma patients treated with radioembolization. Am J Clin Oncol. 2018;41(9):861–6.PubMedPubMedCentralCrossRef Gui B, Weiner AA, Nosher J, et al. Assessment of the albumin-bilirubin (ALBI) grade as a prognostic indicator for hepatocellular carcinoma patients treated with radioembolization. Am J Clin Oncol. 2018;41(9):861–6.PubMedPubMedCentralCrossRef
14.
go back to reference Field KM, Dow C, Michael M. Part I: Liver function in oncology: biochemistry and beyond. Lancet Oncol. 2008;9(11):1092–101.PubMedCrossRef Field KM, Dow C, Michael M. Part I: Liver function in oncology: biochemistry and beyond. Lancet Oncol. 2008;9(11):1092–101.PubMedCrossRef
15.
go back to reference Cucchetti A, Ercolani G, Cescon M, Ravaioli M, Zanello M, Del Gaudio M, Lauro A, Vivarelli M, Grazi GL, Pinna AD. Recovery from liver failure after hepatectomy for hepatocellular carcinoma in cirrhosis: meaning of the model for end-stage liver disease. J Am Coll Surg. 2006;203(5):670–6.PubMedCrossRef Cucchetti A, Ercolani G, Cescon M, Ravaioli M, Zanello M, Del Gaudio M, Lauro A, Vivarelli M, Grazi GL, Pinna AD. Recovery from liver failure after hepatectomy for hepatocellular carcinoma in cirrhosis: meaning of the model for end-stage liver disease. J Am Coll Surg. 2006;203(5):670–6.PubMedCrossRef
16.
go back to reference Balzan S, Belghiti J, Farges O, Ogata S, Sauvanet A, Delefosse D, Durand F. The "50–50 criteria" on postoperative day 5: an accurate predictor of liver failure and death after hepatectomy. Ann Surg. 2005;242(6):824–8 (discussion 828–9)CrossRef Balzan S, Belghiti J, Farges O, Ogata S, Sauvanet A, Delefosse D, Durand F. The "50–50 criteria" on postoperative day 5: an accurate predictor of liver failure and death after hepatectomy. Ann Surg. 2005;242(6):824–8 (discussion 828–9)CrossRef
17.
go back to reference Stockmann M, Lock JF, Riecke B, Heyne K, Martus P, Fricke M, Lehmann S, Niehues SM, Schwabe M, Lemke AJ, 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.PubMedCrossRef Stockmann M, Lock JF, Riecke B, Heyne K, Martus P, Fricke M, Lehmann S, Niehues SM, Schwabe M, Lemke AJ, 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.PubMedCrossRef
18.
go back to reference Fierbinteanu-Braticevici C, Papacocea R, Tribus L, Cristian B. Role of 13C methacetin breath test for non invasive staging of liver fibrosis in patients with chronic hepatitis C. Indian J Med Res. 2014;140(1):123–9.PubMedPubMedCentral Fierbinteanu-Braticevici C, Papacocea R, Tribus L, Cristian B. Role of 13C methacetin breath test for non invasive staging of liver fibrosis in patients with chronic hepatitis C. Indian J Med Res. 2014;140(1):123–9.PubMedPubMedCentral
19.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
20.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
21.
go back to reference Lalazar G, Ilan Y. Assessment of liver function in acute or chronic liver disease by the methacetin breath test: a tool for decision making in clinical hepatology. J Breath Res. 2009;3(4):047001.PubMedCrossRef Lalazar G, Ilan Y. Assessment of liver function in acute or chronic liver disease by the methacetin breath test: a tool for decision making in clinical hepatology. J Breath Res. 2009;3(4):047001.PubMedCrossRef
22.
go back to reference Lock JF, Malinowski M, Seehofer D, Hoppe S, Röhl RI, Niehues SM, Neuhaus P, Stockmann M. Function and volume recovery after partial hepatectomy: influence of preoperative liver function, residual liver volume, and obesity. Langenbecks Arch Surg. 2012;397(8):1297–304.PubMedCrossRef Lock JF, Malinowski M, Seehofer D, Hoppe S, Röhl RI, Niehues SM, Neuhaus P, Stockmann M. Function and volume recovery after partial hepatectomy: influence of preoperative liver function, residual liver volume, and obesity. Langenbecks Arch Surg. 2012;397(8):1297–304.PubMedCrossRef
23.
go back to reference 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(2):139–46.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(2):139–46.CrossRef
24.
go back to reference Lock JF, Schwabauer E, Martus P, Videv N, Pratschke J, Malinowski M, Neuhaus P, Stockmann M. Early diagnosis of primary nonfunction and indication for reoperation after liver transplantation. Liver Transpl. 2010;16(2):172–80.PubMedCrossRef Lock JF, Schwabauer E, Martus P, Videv N, Pratschke J, Malinowski M, Neuhaus P, Stockmann M. Early diagnosis of primary nonfunction and indication for reoperation after liver transplantation. Liver Transpl. 2010;16(2):172–80.PubMedCrossRef
25.
go back to reference Stockmann M, Lock JF, Malinowski M, Seehofer D, Puhl G, Pratschke J, Neuhaus P. How to define initial poor graft function after liver transplantation? A new functional definition by the LiMAx test. Transpl Int. 2010;23(10):1023–32.PubMedCrossRef Stockmann M, Lock JF, Malinowski M, Seehofer D, Puhl G, Pratschke J, Neuhaus P. How to define initial poor graft function after liver transplantation? A new functional definition by the LiMAx test. Transpl Int. 2010;23(10):1023–32.PubMedCrossRef
26.
go back to reference Lock JF, Malinowski M, Schwabauer E, Martus P, Pratschke J, Seehofer D, Puhl G, Neuhaus P, Stockmann M. Initial liver graft function is a reliable predictor of tacrolimus trough levels during the first post-transplant week. Clin Transplant. 2011;25(3):436–43.PubMedCrossRef Lock JF, Malinowski M, Schwabauer E, Martus P, Pratschke J, Seehofer D, Puhl G, Neuhaus P, Stockmann M. Initial liver graft function is a reliable predictor of tacrolimus trough levels during the first post-transplant week. Clin Transplant. 2011;25(3):436–43.PubMedCrossRef
27.
go back to reference Lock JF, Kotobi AN, Malinowski M, Schulz A, Jara M, Neuhaus P, Stockmann M. Predicting the prognosis in acute liver failure: results from a retrospective pilot study using the LiMAx test. Ann Hepatol. 2013;12(4):556–62.PubMedCrossRef Lock JF, Kotobi AN, Malinowski M, Schulz A, Jara M, Neuhaus P, Stockmann M. Predicting the prognosis in acute liver failure: results from a retrospective pilot study using the LiMAx test. Ann Hepatol. 2013;12(4):556–62.PubMedCrossRef
28.
go back to reference Jara M, Malinowski M, Lüttgert K, Schott E, Neuhaus P, Stockmann M. Prognostic value of enzymatic liver function for the estimation of short-term survival of liver transplant candidates: a prospective study with the LiMAx test. Transpl Int. 2015;28(1):52–8.PubMedCrossRef Jara M, Malinowski M, Lüttgert K, Schott E, Neuhaus P, Stockmann M. Prognostic value of enzymatic liver function for the estimation of short-term survival of liver transplant candidates: a prospective study with the LiMAx test. Transpl Int. 2015;28(1):52–8.PubMedCrossRef
29.
go back to reference Hoekstra LT, de Graaf W, Nibourg GA, Heger M, Bennink RJ, Stieger B, van Gulik TM. Physiological and biochemical basis of clinical liver function tests: a review. Ann Surg. 2013;257(1):27–36PubMedCrossRef Hoekstra LT, de Graaf W, Nibourg GA, Heger M, Bennink RJ, Stieger B, van Gulik TM. Physiological and biochemical basis of clinical liver function tests: a review. Ann Surg. 2013;257(1):27–36PubMedCrossRef
30.
go back to reference Schütte K, Seidensticker R, Milbradt O, Bornschein J, Kandulski A, Pech M, Kropf S, Ricke J, Malfertheiner P. Assessment and monitoring of liver function by 13C-aminopyrine breath test after selective transarterial chemoembolisation of hepatocellular carcinoma. Z Gastroenterol. 2015;53(1):21–7.PubMedCrossRef Schütte K, Seidensticker R, Milbradt O, Bornschein J, Kandulski A, Pech M, Kropf S, Ricke J, Malfertheiner P. Assessment and monitoring of liver function by 13C-aminopyrine breath test after selective transarterial chemoembolisation of hepatocellular carcinoma. Z Gastroenterol. 2015;53(1):21–7.PubMedCrossRef
31.
go back to reference Jara M, Bednarsch J, Valle E, Lock JF, Malinowski M, Schulz A, Seehofer D, Jung T, Stockmann M. Reliable assessment of liver function using LiMAx. J Surg Res. 2015;193(1):184–9.PubMedCrossRef Jara M, Bednarsch J, Valle E, Lock JF, Malinowski M, Schulz A, Seehofer D, Jung T, Stockmann M. Reliable assessment of liver function using LiMAx. J Surg Res. 2015;193(1):184–9.PubMedCrossRef
Metadata
Title
Monitoring Liver Function of Patients Undergoing Transarterial Chemoembolization (TACE) by a 13C Breath Test (LiMAx)
Authors
Emona S. Barzakova
Maximilian Schulze-Hagen
Markus Zimmermann
Georg Lurje
Jan Bednarsch
Federico Pedersoli
Peter Isfort
Christiane Kuhl
Philipp Bruners
Publication date
01-12-2019
Publisher
Springer US
Published in
CardioVascular and Interventional Radiology / Issue 12/2019
Print ISSN: 0174-1551
Electronic ISSN: 1432-086X
DOI
https://doi.org/10.1007/s00270-019-02325-3

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