CardioVascular and Interventional Radiology

, Volume 42, Issue 12, pp 1702–1708 | Cite as

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

  • Emona S. BarzakovaEmail author
  • Maximilian Schulze-Hagen
  • Markus Zimmermann
  • Georg Lurje
  • Jan Bednarsch
  • Federico Pedersoli
  • Peter Isfort
  • Christiane Kuhl
  • Philipp Bruners
Clinical Investigation Interventional Oncology
Part of the following topical collections:
  1. Interventional Oncology



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.


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.


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.


TACE Transarterial chemoembolization Liver function LiMAx 



This study was not supported by any funding.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed Consent

For this type of study, formal consent is not required. Consent for publication was obtained for every individual person’s data included in the study.


  1. 1.
    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.PubMedCrossRefGoogle Scholar
  2. 2.
    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):461–9PubMedCrossRefGoogle Scholar
  3. 3.
    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.PubMedCrossRefGoogle Scholar
  4. 4.
    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.PubMedCrossRefGoogle Scholar
  5. 5.
    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.CrossRefGoogle Scholar
  6. 6.
    Gehl J, Omary RA. Transarterial chemoembolization complicated by deteriorating hepatic function. Semin Interv Radiol. 2011;28(2):198–201.CrossRefGoogle Scholar
  7. 7.
    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.PubMedCrossRefGoogle Scholar
  8. 8.
    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.PubMedCrossRefGoogle Scholar
  9. 9.
    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.PubMedCrossRefGoogle Scholar
  10. 10.
    Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–2.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    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.PubMedCrossRefGoogle Scholar
  12. 12.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Field KM, Dow C, Michael M. Part I: Liver function in oncology: biochemistry and beyond. Lancet Oncol. 2008;9(11):1092–101.PubMedCrossRefGoogle Scholar
  15. 15.
    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.PubMedCrossRefGoogle Scholar
  16. 16.
    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)CrossRefGoogle Scholar
  17. 17.
    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.PubMedCrossRefGoogle Scholar
  18. 18.
    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.PubMedPubMedCentralGoogle Scholar
  19. 19.
    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.PubMedCrossRefGoogle Scholar
  20. 20.
    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.PubMedCrossRefGoogle Scholar
  21. 21.
    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.PubMedCrossRefGoogle Scholar
  22. 22.
    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.PubMedCrossRefGoogle Scholar
  23. 23.
    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.CrossRefGoogle Scholar
  24. 24.
    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.PubMedCrossRefGoogle Scholar
  25. 25.
    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.PubMedCrossRefGoogle Scholar
  26. 26.
    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.PubMedCrossRefGoogle Scholar
  27. 27.
    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.PubMedCrossRefGoogle Scholar
  28. 28.
    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.PubMedCrossRefGoogle Scholar
  29. 29.
    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):27–36PubMedCrossRefGoogle Scholar
  30. 30.
    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.PubMedCrossRefGoogle Scholar
  31. 31.
    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.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2019

Authors and Affiliations

  • Emona S. Barzakova
    • 1
    Email author
  • Maximilian Schulze-Hagen
    • 1
  • Markus Zimmermann
    • 1
  • Georg Lurje
    • 2
  • Jan Bednarsch
    • 2
  • Federico Pedersoli
    • 1
  • Peter Isfort
    • 1
  • Christiane Kuhl
    • 1
  • Philipp Bruners
    • 1
  1. 1.Department of Diagnostic and Interventional RadiologyUniversity Hospital RWTH AachenAachenGermany
  2. 2.Department of Surgery and TransplantationUniversity Hospital RWTH AachenAachenGermany

Personalised recommendations