Reply to the Letter to the Editor ‘Improving MELD for use in acute liver failure’
Authors: Christoph Jochum, Lars Bechmann, Ali Canbay
Journal: Journal of Hepatology (2010)

Improving MELD for use in acute liver failureJournal of HepatologyVol. 54Issue 6PreviewBechmann et al. [1] presented an interesting modification to the Model for End-Stage Liver Disease (MELD) score using M-65, a marker of hepatic necrosis, as a substitute for bilirubin in the MELD equation which they subsequently applied to a series of patients with acute liver failure (ALF). The statistical justification and reporting of the subsequent results is useful to discuss. Full-Text PDF Open Access This is a reply to the Letter to the Editor by Dr. McPhail: The authors thank Dr. McPhail for initiating this valuable discussion on our manuscript. We agree with Dr. McPhail that the MELD score was initially developed to stratify the risk of death in a cohort of patients with end-stage chronic liver disease to predict death after a TIPS procedure, as we pointed out in the introduction of the original manuscript [1Malinchoc M. Kamath P.S. Gordon F.D. Peine C.J. Rank J. ter Borg P.C. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts.Hepatology. 2000; 31: 864-871Crossref PubMed Scopus (2058) Google Scholar, 2Bechmann L.P. Jochum C. Kocabayoglu P. Sowa J.P. Kassalik M. Gieseler R.K. et al.Cytokeratin 18-based modification of the MELD score improves prediction of spontaneous survival after acute liver injury.J Hepatol. 2010; 53: 639-647Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar]. We thus agree with Dr. McPhail that the MELD score was neither primarily designed as an allocation tool for patients with end-stage liver disease, nor as a tool to predict outcome in acute liver failure (ALF). However, to date, the MELD score in its current form, without adaptation of the original regression coefficients used in the original Mayo model, is widely used to allocate grafts for patients with end-stage liver disease; it was found to predict survival and thus the need for transplantation better than the previously used waiting list and Child-Pugh classification [[3]Cholongitas E. Germani G. Burroughs A.K. Prioritization for liver transplantation.Nat Rev Gastroenterol Hepatol. 2010; 7: 659-668Crossref PubMed Scopus (49) Google Scholar]. In particular, the low frequency of viral liver diseases in the original Mayo cohort is contradictory to current observations that the number of transplantations due to HCV cirrhosis is dramatically rising. Thus, it is questionable whether the original regression calculations reflect the overall patient population with end-stage liver diseases of the present date. However, UNOS and Eurotransplant make use of the original formula and the current MELD formula is considered the gold standard in organ allocation, worldwide. Furthermore, several recent publications used the original Mayo formula to predict survival in ALF and found the MELD to be superior to previous calculations (i.e. KCC) [4Yantorno S.E. Kremers W.K. Ruf A.E. Trentadue J.J. Podesta L.G. Villamil F.G. MELD is superior to King’s college and Clichy’s criteria to assess prognosis in fulminant hepatic failure.Liver Transplant. 2007; 13: 822-828Crossref PubMed Scopus (140) Google Scholar, 5Dhiman R.K. Jain S. Maheshwari U. Bhalla A. Sharma N. Ahluwalia J. et al.Early indicators of prognosis in fulminant hepatic failure: an assessment of the model for end-stage liver disease (MELD) and King’s College Hospital criteria.Liver Transplant. 2007; 13: 814-821Crossref PubMed Scopus (111) Google Scholar]. We observed that (i) bilirubin values are of no predictive value within the MELD calculation regarding survival of ALF patients and that (ii) the circulating CK18 as assessed by M65 ELISA is of good prognostic value in this cohort. (iii) When we replaced bilirubin with M65 in the original formula, we found a dramatic improvement of predictive value in our cohort of ALF patients (Fig. 1). The aim of our study was to identify tools to predict if a particular patient needs a transplant, or if her/his liver has the capacity to regenerate spontaneously, a situation which rarely occurs in chronic liver disease. Therefore, we chose the outcome as an endpoint rather than time to death or transplantation. We agree with Dr. McPhail that ideally, the development of a multivariate regression model would improve the quality of the modified MELD as well as the original MELD calculations. However, the available sample size was underpowered for this type of statistical method; for this reason, we decided to perform these analyses after a validation period with a larger patient cohort in a currently initiated prospective study. This is especially important since we might identify even better predictors, depending on the different etiologies of ALF in a larger cohort. At the end, we agree that statistical models are not directly interchangeable between different diseases and populations, thus repeated modelling is necessary to improve the validity of a model, which was also suggested by D. Samuel [[6]Samuel D. Ichai P. Prognosis indicator in acute liver failure: Is there a place for cell death markers?.J Hepatol. 2010; 53: 593-595Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar]. We continue to include data from more patients in order to validate our model and perform multivariate regression analysis. Due to the fortunately rare disease, a registry of ALF-patients in Europe would enhance the available patient numbers and thus help to further improve our understanding and management of these patients. CJ, LPB and AC have no conflicts of interest and are supported by the DFG, Germany.