Digestive Diseases and Sciences

, Volume 64, Issue 2, pp 576–584 | Cite as

Prospective Assessment of Liver Function by an Enzymatic Liver Function Test to Estimate Short-Term Survival in Patients with Liver Cirrhosis

  • Maximilian JaraEmail author
  • Tomasz Dziodzio
  • Maciej Malinowski
  • Katja Lüttgert
  • Radoslav Nikolov
  • Paul Viktor Ritschl
  • Robert Öllinger
  • Johann Pratschke
  • Martin Stockmann
Original Article



MELD attempts to objectively predict the risk of mortality of patients with liver cirrhosis and is commonly used to prioritize organ allocation. Despite the usefulness of the MELD, updated metrics could further improve the accuracy of estimates of survival.


To assess and compare the prognostic ability of an enzymatic 13C-based liver function test (LiMAx) and distinct markers of liver function to predict 3-month mortality of patients with chronic liver failure.


We prospectively investigated liver function of 268 chronic liver failure patients without hepatocellular carcinoma. Primary study endpoint was liver-related death within 3 months of follow-up. Prognostic values were calculated using Cox proportional hazards and logistic regression analysis.


The Cox proportional hazard model indicated that LiMAx (p < 0.001) and serum creatinine values (p < 0.001) were the significant parameters independently associated with the risk of liver failure-related death. Logistic regression analysis revealed LiMAx and serum creatinine to be independent predictors of mortality. Areas under the receiver-operating characteristic curves for MELD (0.86 [0.80–0.92]) and for a combined score of LiMAx and serum creatinine (0.83 [0.76–0.90]) were comparable.


Apart from serum creatinine levels, enzymatic liver function measured by LiMAx was found to be an independent predictor of short-term mortality risk in patients with liver cirrhosis. A risk score combining both determinants allows reliable prediction of short-term prognosis considering actual organ function.

Trial Registration Number (German Clinical Trials Register) # DRKS00000614.


End-stage liver disease Liver function test LiMAx MELD Risk assessment Survival 



Area under the receiver-operating characteristics


Confidence interval


Child–Pugh score


End-stage liver disease




Hepatitis C virus


Hazard ratio


Intraclass correlation coefficient


International normalized ratio


Interquartile range


Maximum liver function capacity


Liver transplantation


Model for end-stage liver disease


Sodium MELD


Nonalcoholic fatty liver disease


Regression coefficient


Receiver-operating characteristic


Spontaneous bacterial peritonitis






Standard deviation


United Kingdom Model for End-Stage Liver Disease



We gratefully thank Ms. Antonia Rothkäppel for the performance of LiMAx measurements. Further, we want to thank Alexander Krannich and Prof. Dr. rer. nat. habil. Klaus-Dieter Wernecke for performing statistical analyses. We also want to thank Mr. Jim Orr and Mr. Andrzej Juraszek for editing the final manuscript.


This study was part of the d-LIVER project and was funded in part by a Grant from the European Commission’s Seventh Framework Programme/European Research Council, grant agreement number 287596.

Compliance with ethical standards

Conflict of interest

Martin Stockmann is the inventor of the LiMAx test and has capital interest in Humedics, the company marketing the LiMAx test. Maximilian Jara and James Orr disclose having received research Grants in order of the d-LIVER European Commission’s Seventh Framework Programme/European Research Council, Grant Agreement Number 287596— Martin Stockmann was also steering committee member for the d-LIVER project. Remaining authors who have taken part in this study declared no conflict of interest with respect to this manuscript.

Supplementary material

10620_2018_5360_MOESM1_ESM.docx (42 kb)
Supplementary material 1 (DOCX 41 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Maximilian Jara
    • 1
    Email author
  • Tomasz Dziodzio
    • 1
  • Maciej Malinowski
    • 1
    • 2
  • Katja Lüttgert
    • 1
  • Radoslav Nikolov
    • 1
  • Paul Viktor Ritschl
    • 1
    • 3
  • Robert Öllinger
    • 1
  • Johann Pratschke
    • 1
  • Martin Stockmann
    • 1
    • 4
  1. 1.Department of Surgery, Campus Charité Mitte - Campus Virchow-KlinikumCharité - Universitätsmedizin BerlinBerlinGermany
  2. 2.Department of General, Visceral, Vascular and Pediatric SurgeryUniversity of The SaarlandHomburgGermany
  3. 3.BIH Charité Clinician Scientist ProgramBerlin Institute of Health (BIH)BerlinGermany
  4. 4.Department of General, Visceral and Vascular SurgeryEvangelisches Krankenhaus Paul Gerhardt StiftLutherstadt WittenbergGermany

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