Research Article| Volume 68, ISSUE 4, P707-714, April 2018

Download started.


A model including sarcopenia surpasses the MELD score in predicting waiting list mortality in cirrhotic liver transplant candidates: A competing risk analysis in a national cohort

Published:December 05, 2017DOI:


      • Sarcopenia is associated with waiting list mortality in liver transplant patients.
      • Adding sarcopenia to the MELD score does not have any added value for prioritization.
      • However, patients with a low MELD score and sarcopenia may be under prioritized.
      • Our model may be used to identify patients at risk for waiting list mortality.

      Background & Aims

      Frail patients with low model for end-stage liver disease (MELD) scores may be under-prioritised. Low skeletal muscle mass, namely sarcopenia, has been identified as a risk factor for waiting list mortality. A recent study proposed incorporating sarcopenia in the MELD score (MELD-Sarcopenia score). We aimed to investigate the association between sarcopenia and waiting list mortality, and to validate the MELD-Sarcopenia score (i.e. MELD + 10.35 * Sarcopenia).


      We identified consecutive patients with cirrhosis listed for liver transplantation in the Eurotransplant registry between 2007–2014 and measured skeletal muscle mass on computed tomography. A competing risk analysis was used to compare survival of patients with and without sarcopenia, and concordance (c) indices were calculated to assess performance of the MELD and MELD-Sarcopenia score. We created a nomogram of the best predictive model.


      We included 585 patients with a median MELD score of 14 (interquartile range 9–19), of which 254 (43.4%) were identified as having sarcopenia. Median waiting list survival was shorter in patients with sarcopenia than those without (p <0.001). This effect was even more pronounced in patients with MELD ≤15. The discriminative performance of the MELD-Sarcopenia score (c-index 0.820) for three-month mortality was lower than MELD score alone (c-index 0.839). Apart from sarcopenia and MELD score, other predictive variables were occurrence of hepatic encephalopathy before listing and recipient age. A model including all these variables yielded a c-index of 0.851.


      Sarcopenia was associated with waiting list mortality in liver transplant candidates with cirrhosis, particularly in patients with lower MELD scores. The MELD-Sarcopenia score was successfully validated in this cohort. However, incorporating sarcopenia in the MELD score had limited added value in predicting waiting list mortality.

      Lay summary

      In this study among patients with liver cirrhosis listed for liver transplantation, low skeletal muscle mass was associated with mortality on the waiting list, particularly in patients who were listed with low priority based on a low MELD score. However, adding these measurements to the currently used system for donor and organ allocation showed no added value.

      Graphical abstract


      Linked Article

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Hepatology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


      Author names in bold designate shared co-first authorship

        • Freeman Jr., R.B.
        • Wiesner R.H.
        • Harper A.
        • McDiarmid S.V.
        • Lake J.
        • Edwards E.
        • et al.
        The new liver allocation system: moving toward evidence-based transplantation policy.
        Liver Transpl. 2002; 8: 851-858
        • Kamath P.S.
        • Kim W.R.
        Advanced Liver Disease Study G. The model for end-stage liver disease (MELD).
        Hepatology. 2007; 45: 797-805
        • Kim W.R.
        • Biggins S.W.
        • Kremers W.K.
        • Wiesner R.H.
        • Kamath P.S.
        • Benson J.T.
        • et al.
        Hyponatremia and mortality among patients on the liver-transplant waiting list.
        N Engl J Med. 2008; 359: 1018-1026
        • Myers R.P.
        • Shaheen A.A.
        • Faris P.
        • Aspinall A.I.
        • Burak K.W.
        Revision of MELD to include serum albumin improves prediction of mortality on the liver transplant waiting list.
        PLoS One. 2013; 8: e51926
        • Myers R.P.
        • Tandon P.
        • Ney M.
        • Meeberg G.
        • Faris P.
        • Shaheen A.A.
        • et al.
        Validation of the five-variable Model for End-stage Liver Disease (5vMELD) for prediction of mortality on the liver transplant waiting list.
        Liver Int. 2014; 34: 1176-1183
        • Durand F.
        • Buyse S.
        • Francoz C.
        • Laouenan C.
        • Bruno O.
        • Belghiti J.
        • et al.
        Prognostic value of muscle atrophy in cirrhosis using psoas muscle thickness on computed tomography.
        J Hepatol. 2014; 60: 1151-1157
        • Lai J.C.
        • Dodge J.L.
        • Sen S.
        • Covinsky K.
        • Feng S.
        Functional decline in patients with cirrhosis awaiting liver transplantation: Results from the functional assessment in liver transplantation (FrAILT) study.
        Hepatology. 2016; 63: 574-580
        • Lai J.C.
        • Feng S.
        • Terrault N.A.
        • Lizaola B.
        • Hayssen H.
        • Covinsky K.
        Frailty predicts waitlist mortality in liver transplant candidates.
        Am J Transplant. 2014; 14: 1870-1879
        • van Vugt J.L.
        • Levolger S.
        • de Bruin R.W.
        • van Rosmalen J.
        • Metselaar H.J.
        • IJzermans J.N.
        Systematic review and meta-analysis of the impact of computed tomography assessed skeletal muscle mass on outcome in patients awaiting or undergoing liver transplantation.
        Am J Transplant. 2016; 16: 2277-2292
        • Montano-Loza A.J.
        • Duarte-Rojo A.
        • Meza-Junco J.
        • Baracos V.E.
        • Sawyer M.B.
        • Pang J.X.
        • et al.
        Inclusion of sarcopenia within MELD (MELD-Sarcopenia) and the prediction of mortality in patients with cirrhosis.
        Clin Transl Gastroenterol. 2015; 6: e102
        • Meza-Junco J.
        • Montano-Loza A.J.
        • Baracos V.E.
        • Prado C.M.
        • Bain V.G.
        • Beaumont C.
        • et al.
        Sarcopenia as a prognostic index of nutritional status in concurrent cirrhosis and hepatocellular carcinoma.
        J Clin Gastroenterol. 2013; 47: 861-870
        • Montano-Loza A.J.
        • Meza-Junco J.
        • Prado C.M.
        • Lieffers J.R.
        • Baracos V.E.
        • Bain V.G.
        • et al.
        Muscle wasting is associated with mortality in patients with cirrhosis.
        Clin Gastroenterol Hepatol. 2012; 10 ([173 e161]): 166-173
        • Tandon P.
        • Ney M.
        • Irwin I.
        • Ma M.M.
        • Gramlich L.
        • Bain V.G.
        • et al.
        Severe muscle depletion in patients on the liver transplant wait list: its prevalence and independent prognostic value.
        Liver Transpl. 2012; 18: 1209-1216
        • Yadav A.
        • Chang Y.H.
        • Carpenter S.
        • Silva A.C.
        • Rakela J.
        • Aqel B.A.
        • et al.
        Relationship between sarcopenia, six-minute walk distance and health-related quality of life in liver transplant candidates.
        Clin Transplant. 2015; 29: 134-141
        • Montano-Loza A.J.
        • Angulo P.
        • Meza-Junco J.
        • Prado C.M.
        • Sawyer M.B.
        • Beaumont C.
        • et al.
        Sarcopenic obesity and myosteatosis are associated with higher mortality in patients with cirrhosis.
        J Cachexia Sarcopenia Muscle. 2016; 7: 126-135
        • Giusto M.
        • Lattanzi B.
        • Albanese C.
        • Galtieri A.
        • Farcomeni A.
        • Giannelli V.
        • et al.
        Sarcopenia in liver cirrhosis: the role of computed tomography scan for the assessment of muscle mass compared with dual-energy X-ray absorptiometry and anthropometry.
        Eur J Gastroenterol Hepatol. 2015; 27: 328-334
        • Noordzij M.
        • Leffondre K.
        • van Stralen K.J.
        • Zoccali C.
        • Dekker F.W.
        • Jager K.J.
        When do we need competing risks methods for survival analysis in nephrology?.
        Nephrol Dial Transplant. 2013; 28: 2670-2677
        • Sapir-Pichhadze R.
        • Pintilie M.
        • Tinckam K.J.
        • Laupacis A.
        • Logan A.G.
        • Beyene J.
        • et al.
        Survival analysis in the presence of competing risks: the example of waitlisted kidney transplant candidates.
        Am J Transplant. 2016; 16: 1958-1966
      1. Eurotransplant. 2017 [cited 27-04-2017]; Available from:

        • Mazzaferro V.
        • Regalia E.
        • Doci R.
        • Andreola S.
        • Pulvirenti A.
        • Bozzetti F.
        • et al.
        Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis.
        N Engl J Med. 1996; 334: 693-699
        • van Vledder M.G.
        • Levolger S.
        • Ayez N.
        • Verhoef C.
        • Tran T.C.
        • Ijzermans J.N.
        Body composition and outcome in patients undergoing resection of colorectal liver metastases.
        Br J Surg. 2012; 99: 550-557
        • Shen W.
        • Punyanitya M.
        • Wang Z.
        • Gallagher D.
        • St-Onge M.P.
        • Albu J.
        • et al.
        Total body skeletal muscle and adipose tissue volumes: estimation from a single abdominal cross-sectional image.
        J Appl Physiol. 1985; 2004: 2333-2338
        • van Vugt J.L.
        • Levolger S.
        • Gharbharan A.
        • Koek M.
        • Niessen W.J.
        • Burger J.W.
        • et al.
        A comparative study of software programmes for cross-sectional skeletal muscle and adipose tissue measurements on abdominal computed tomography scans of rectal cancer patients.
        J Cachexia Sarcopenia Muscle. 2017; 8: 285-297
        • Martin L.
        • Birdsell L.
        • Macdonald N.
        • Reiman T.
        • Clandinin M.T.
        • McCargar L.J.
        • et al.
        Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index.
        J Clin Oncol. 2013; 31: 1539-1547
        • Carey E.J.
        • Lai J.C.
        • Wang C.W.
        • Dasarathy S.
        • Lobach I.
        • Montano-Loza A.J.
        • et al.
        A multi-center study to define sarcopenia in patients with end-stage liver disease.
        Liver Transpl. 2017; 23: 625-633
        • Wolbers M.
        • Blanche P.
        • Koller M.T.
        • Witteman J.C.
        • Gerds T.A.
        Concordance for prognostic models with competing risks.
        Biostatistics. 2014; 15: 526-539
        • Wolbers M.
        • Koller M.T.
        • Witteman J.C.
        • Steyerberg E.W.
        Prognostic models with competing risks: methods and application to coronary risk prediction.
        Epidemiology. 2009; 20: 555-561
        • Fine J.
        • Gray R.
        A proportional hazards model for the subdistribution of a competing risk.
        J Am Stat Assoc. 1999; 94: 496-509
        • Buettner S.
        • Wagner D.
        • Kim Y.
        • Margonis G.A.
        • Makary M.A.
        • Wilson A.
        • et al.
        Inclusion of sarcopenia outperforms the modified frailty index in predicting 1-year mortality among 1,326 patients undergoing gastrointestinal surgery for a malignant indication.
        J Am Coll Surg. 2016; 222: e392
        • Collins G.S.
        • Reitsma J.B.
        • Altman D.G.
        • Moons K.G.
        Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD): the TRIPOD Statement.
        Br J Surg. 2015; 102: 148-158
        • Rutten I.J.
        • Ubachs J.
        • Kruitwagen R.F.P.M.
        • Beets-Tan R.G.H.
        • Olde Damink S.W.M.
        • van Gorp T.
        Abstracts of the 9th International Conference on Cachexia, Sarcopenia, and Muscle Wasting, Berlin, Germany, 10–11 December 2016 (part 2) (1-45: Psoas muscle measurements are inferior to total skeletal muscle measurements in the assessment of sarcopenia in ovarian cancer).
        J Cachexia Sarcopenia Muscle. 2017; 8: 161-183
        • Baracos V.E.
        Psoas as a sentinel muscle for sarcopenia: a flawed premise.
        J Cachexia Sarcopenia Muscle. 2017; 8: 527-528
        • Golse N.
        • Bucur P.O.
        • Ciacio O.
        • Pittau G.
        • Sa Cunha A.
        • Adam R.
        • et al.
        A new definition of sarcopenia in patients with cirrhosis undergoing liver transplantation.
        Liver Transpl. 2017; 23: 143-154
        • Hamaguchi Y.
        • Kaido T.
        • Okumura S.
        • Kobayashi A.
        • Shirai H.
        • Yagi S.
        • et al.
        Proposal of muscle-MELD score, including muscularity, for prediction of mortality after living donor liver transplantation.
        Transplantation. 2016; 100: 2416-2423
        • Dasarathy S.
        • Merli M.
        Sarcopenia from mechanism to diagnosis and treatment in liver disease.
        J Hepatol. 2016; 65: 1232-1244
        • Robins J.M.
        • Finkelstein D.M.
        Correcting for noncompliance and dependent censoring in an AIDS Clinical Trial with inverse probability of censoring weighted (IPCW) log-rank tests.
        Biometrics. 2000; 56: 779-788
        • Takahashi N.
        • Sugimoto M.
        • Psutka S.P.
        • Chen B.
        • Moynagh M.R.
        • Carter R.E.
        Validation study of a new semi-automated software program for CT body composition analysis.
        Abdom Radiol. 2017; 42: 2369-2375
        • Popuri K.
        • Cobzas D.
        • Esfandiari N.
        • Baracos V.
        • Jagersand M.
        Body composition assessment in axial CT images using FEM-based automatic segmentation of skeletal muscle.
        IEEE Trans Med Imaging. 2016; 35: 512-520