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MELD in liver transplantation: the da Vinci code for the Holy Grail?

2005; Elsevier BV; Volume: 42; Issue: 4 Linguagem: Inglês

10.1016/j.jhep.2005.02.003

1600-0641

Teh‐Ia Huo, Jaw‐Ching Wu, Shou‐Dong Lee,

Organ Transplantation Techniques and Outcomes

We read with interest the paper published in a recent issue of the Journal of Hepatology under the heading of Forum on Liver Transplantation [[1]Freeman R.B. MELD: the holy grail of organ allocation?.J Hepatol. 2005; 42: 16-20Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar]. The model for end-stage liver disease (MELD) has become the prevailing criteria for organ allocation in liver transplantation. Abundant studies have shown that the MELD system is superior or at least equal to the traditional Child-Turcott-Pugh (CTP) system in terms of outcome prediction for patients with end-stage liver disease [2Wiesner R. Edwards E. Freeman R. Harper A. Kim R. Kamath P. et al.the United Network For Organ Sharing Liver Disease Severity Score Committee. Model for end-stage liver disease (MELD) and allocation of donor livers.Gastroenterology. 2003; 124: 91-96Abstract Full Text Full Text PDF PubMed Scopus (1938) Google Scholar, 3Said A. Williams J. Holden J. Remington P. Gangnon R. Musat A. et al.Model for end stage liver disease score predicts mortality across a broad spectrum of liver disease.J Hepatol. 2004; 40: 897-903Abstract Full Text Full Text PDF PubMed Google Scholar, 4Salerno F. Merli M. Cazzaniga M. Valeriano V. Rossi P. Lovaria A. et al.MELD score is better than Child-Pugh score in predicting 3-month survival of patients undergoing transjugular intrahepatic portosystemic shunt.J Hepatol. 2002; 36: 494-500Abstract Full Text Full Text PDF PubMed Scopus (214) Google Scholar, 5Giannini E. Botta F. Testa R. Utility of the MELD score for assessing 3-month survival in patients with liver cirrhosis: one more positive answer.Gastroenterology. 2003; 125: 993-994Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar, 6Angermayr B. Cejna M. Karnel F. Gschwantler M. Koenig F. Pidlich J. et al.Child-Pugh versus MELD score in predicting survival in patients undergoing transjugular intrahepatic portosystemic shunt.Gut. 2003; 52: 879-885Crossref PubMed Scopus (232) Google Scholar]. It possesses the advantage of minimal variability and wide-range continuous scale to assess underlying disease severity compared to the traditional CTP scoring system. However, the MELD system may not serve all patients well and could have certain limitations. We have investigated the impact of the occurrence of cirrhosis-related complications (esophageal varices bleeding, spontaneous bacterial peritonitis or hepatic encephalopathy) on patient survival in comparison with the MELD score. Patients with these complications had a similar baseline MELD score compared to those without complications, yet they had a much poorer prognosis. Among 290 patients with CTP score of 7 or more, the mean MELD score was 11.6±2.9 for patients with complications (n=67), compared to a mean MELD score of 12.2±3.2 (P=0.184) for those without complications (n=223) at disease presentation (unpublished data). Interestingly, the presence of complications had a very similar profile of predictive accuracy for short and intermediate term mortality compared to the MELD system by using the c-statistic method for the area under receiver operating characteristics curve. These findings suggest that while these patients have a poor prognosis and early transplantation referral is recommended, they do not necessarily have a higher MELD score and the priority for transplantation could be down-staged in the MELD era.As indicated by the author, patients with hepatocellular carcinoma (HCC) awaiting liver transplantation are a particular group in organ allocation. The UNOS has arbitrarily set up a MELD score of 24 for stage 2 (T2) HCC patients based on an anticipated 15% risk of drop out from the waiting list. However, this score could be overestimated according to our recent survey [[7]Huo T.I. Wu J.C. Lin H.C. Lee F.Y. Hou M.C. Huang Y.H. et al.Determination of the optimal model for end-stage liver disease score in patients with small hepatocellular carcinoma undergoing loco-regional therapy.Liver Transpl. 2004; 10: 1507-1513Crossref PubMed Scopus (18) Google Scholar], because patients with small HCC can often be effectively treated with various loco-regional tumor ablation therapies that slow down the rate of tumor progression. The tumor progression (or de-listing) rate for T2 stage HCC at 1-year was 13.8%, approximately equal to the 1-year mortality rate of 13.9% for patients with MELD score range of 10–14 in the cirrhosis group without HCC [[7]Huo T.I. Wu J.C. Lin H.C. Lee F.Y. Hou M.C. Huang Y.H. et al.Determination of the optimal model for end-stage liver disease score in patients with small hepatocellular carcinoma undergoing loco-regional therapy.Liver Transpl. 2004; 10: 1507-1513Crossref PubMed Scopus (18) Google Scholar].According to the current UNOS policy, the priority of liver transplantation is determined based on a single-point estimation of MELD score. The change of MELD score over time (ΔMELD), which measures the dynamic change of liver reserve, may provide updated information of disease severity and could alter the ranking status. However, the prognostic value of serial determinations of MELD score has not been fully elucidated in a recent study [[8]Bambha K. Kim W.R. Kremers W.K. Therneau T.M. Kamath P.S. Wiesner R. et al.Predicting survival among patients listed for liver transplantation: an assessment of serial MELD measurements.Am J Transpl. 2004; 4: 1798-1804Crossref PubMed Scopus (98) Google Scholar]. By contrast, our recent study showed that increasing MELD score is associated with the onset of ascites and hepatic encephalopathy, and ΔMELD is superior to initial MELD and CTP score to predict the outcome in patients with advanced cirrhosis [[9]Huo TI, Wu JC, Lin HC, Lee FY, Hou MC, Huang YH, et al. Evaluation of the increase in model for end-stage liver disease (MELD) score over time as a prognostic predictor in patients with advanced liver cirrhosis: risk factor analysis and comparison with initial MELD and Child-Turcotte-Pugh score. J Hepatol; in press.Google Scholar].We are convinced that the MELD system is particularly useful as a tool to fairly allocate donor organs in a large patient population as a whole. Nevertheless, patients awaiting transplantation could have different clinical scenarios and may not be equally weighted even they have the same MELD score. Analogous to the situation of pursuing the Holy Grail from the Da Vinci Code according to a recent famous novel, the MELD ‘code’, which leads to a presumably right way of defining the priority of organ allocation, does not necessarily reveal the fundamental myth or adequately solve the controversies in the current practice of organ transplantation. Since the patient population awaiting transplantation is intrinsically heterogeneous, other more potent biological markers with a better predictive ability should be continuously explored for further refinement. We read with interest the paper published in a recent issue of the Journal of Hepatology under the heading of Forum on Liver Transplantation [[1]Freeman R.B. MELD: the holy grail of organ allocation?.J Hepatol. 2005; 42: 16-20Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar]. The model for end-stage liver disease (MELD) has become the prevailing criteria for organ allocation in liver transplantation. Abundant studies have shown that the MELD system is superior or at least equal to the traditional Child-Turcott-Pugh (CTP) system in terms of outcome prediction for patients with end-stage liver disease [2Wiesner R. Edwards E. Freeman R. Harper A. Kim R. Kamath P. et al.the United Network For Organ Sharing Liver Disease Severity Score Committee. Model for end-stage liver disease (MELD) and allocation of donor livers.Gastroenterology. 2003; 124: 91-96Abstract Full Text Full Text PDF PubMed Scopus (1938) Google Scholar, 3Said A. Williams J. Holden J. Remington P. Gangnon R. Musat A. et al.Model for end stage liver disease score predicts mortality across a broad spectrum of liver disease.J Hepatol. 2004; 40: 897-903Abstract Full Text Full Text PDF PubMed Google Scholar, 4Salerno F. Merli M. Cazzaniga M. Valeriano V. Rossi P. Lovaria A. et al.MELD score is better than Child-Pugh score in predicting 3-month survival of patients undergoing transjugular intrahepatic portosystemic shunt.J Hepatol. 2002; 36: 494-500Abstract Full Text Full Text PDF PubMed Scopus (214) Google Scholar, 5Giannini E. Botta F. Testa R. Utility of the MELD score for assessing 3-month survival in patients with liver cirrhosis: one more positive answer.Gastroenterology. 2003; 125: 993-994Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar, 6Angermayr B. Cejna M. Karnel F. Gschwantler M. Koenig F. Pidlich J. et al.Child-Pugh versus MELD score in predicting survival in patients undergoing transjugular intrahepatic portosystemic shunt.Gut. 2003; 52: 879-885Crossref PubMed Scopus (232) Google Scholar]. It possesses the advantage of minimal variability and wide-range continuous scale to assess underlying disease severity compared to the traditional CTP scoring system. However, the MELD system may not serve all patients well and could have certain limitations. We have investigated the impact of the occurrence of cirrhosis-related complications (esophageal varices bleeding, spontaneous bacterial peritonitis or hepatic encephalopathy) on patient survival in comparison with the MELD score. Patients with these complications had a similar baseline MELD score compared to those without complications, yet they had a much poorer prognosis. Among 290 patients with CTP score of 7 or more, the mean MELD score was 11.6±2.9 for patients with complications (n=67), compared to a mean MELD score of 12.2±3.2 (P=0.184) for those without complications (n=223) at disease presentation (unpublished data). Interestingly, the presence of complications had a very similar profile of predictive accuracy for short and intermediate term mortality compared to the MELD system by using the c-statistic method for the area under receiver operating characteristics curve. These findings suggest that while these patients have a poor prognosis and early transplantation referral is recommended, they do not necessarily have a higher MELD score and the priority for transplantation could be down-staged in the MELD era. As indicated by the author, patients with hepatocellular carcinoma (HCC) awaiting liver transplantation are a particular group in organ allocation. The UNOS has arbitrarily set up a MELD score of 24 for stage 2 (T2) HCC patients based on an anticipated 15% risk of drop out from the waiting list. However, this score could be overestimated according to our recent survey [[7]Huo T.I. Wu J.C. Lin H.C. Lee F.Y. Hou M.C. Huang Y.H. et al.Determination of the optimal model for end-stage liver disease score in patients with small hepatocellular carcinoma undergoing loco-regional therapy.Liver Transpl. 2004; 10: 1507-1513Crossref PubMed Scopus (18) Google Scholar], because patients with small HCC can often be effectively treated with various loco-regional tumor ablation therapies that slow down the rate of tumor progression. The tumor progression (or de-listing) rate for T2 stage HCC at 1-year was 13.8%, approximately equal to the 1-year mortality rate of 13.9% for patients with MELD score range of 10–14 in the cirrhosis group without HCC [[7]Huo T.I. Wu J.C. Lin H.C. Lee F.Y. Hou M.C. Huang Y.H. et al.Determination of the optimal model for end-stage liver disease score in patients with small hepatocellular carcinoma undergoing loco-regional therapy.Liver Transpl. 2004; 10: 1507-1513Crossref PubMed Scopus (18) Google Scholar]. According to the current UNOS policy, the priority of liver transplantation is determined based on a single-point estimation of MELD score. The change of MELD score over time (ΔMELD), which measures the dynamic change of liver reserve, may provide updated information of disease severity and could alter the ranking status. However, the prognostic value of serial determinations of MELD score has not been fully elucidated in a recent study [[8]Bambha K. Kim W.R. Kremers W.K. Therneau T.M. Kamath P.S. Wiesner R. et al.Predicting survival among patients listed for liver transplantation: an assessment of serial MELD measurements.Am J Transpl. 2004; 4: 1798-1804Crossref PubMed Scopus (98) Google Scholar]. By contrast, our recent study showed that increasing MELD score is associated with the onset of ascites and hepatic encephalopathy, and ΔMELD is superior to initial MELD and CTP score to predict the outcome in patients with advanced cirrhosis [[9]Huo TI, Wu JC, Lin HC, Lee FY, Hou MC, Huang YH, et al. Evaluation of the increase in model for end-stage liver disease (MELD) score over time as a prognostic predictor in patients with advanced liver cirrhosis: risk factor analysis and comparison with initial MELD and Child-Turcotte-Pugh score. J Hepatol; in press.Google Scholar]. We are convinced that the MELD system is particularly useful as a tool to fairly allocate donor organs in a large patient population as a whole. Nevertheless, patients awaiting transplantation could have different clinical scenarios and may not be equally weighted even they have the same MELD score. Analogous to the situation of pursuing the Holy Grail from the Da Vinci Code according to a recent famous novel, the MELD ‘code’, which leads to a presumably right way of defining the priority of organ allocation, does not necessarily reveal the fundamental myth or adequately solve the controversies in the current practice of organ transplantation. Since the patient population awaiting transplantation is intrinsically heterogeneous, other more potent biological markers with a better predictive ability should be continuously explored for further refinement.