Impact of the Model for End-Stage Liver Disease (MELD) Score on Liver Transplantation in Greece A. Karapanagiotoua,*, C. Kydonaa, C. Dimitriadisb, S. Papadopoulosa, T. Theodoridoua, T. Tholiotia, G. Fouzasc, G. Imvriosc, and N. Gritsi-Gerogiannia a Intensive Care Unit “Hippokratio” Hospital, Thessaloniki, Greece; bDepartment of Nephrology “Hippokratio” Hospital, Thessaloniki, Greece; and cDepartment of Surgery and Transplantation “Hippokratio” Hospital, Thessaloniki, Greece
ABSTRACT Introduction. The impact of preoperative Model for End-stage Liver Disease (MELD) score in postoperative mortality remains unclear. The assumption that patients with a higher MELD score will have a higher mortality rate is not confirmed and studies are contradictory. Aim. The study of the clinical course of patients with a higher MELD score and its impact in immediate and later mortality in comparison with patients with a lower MELD score in the only liver transplantation center in Greece. Method. We retrospectively studied 71 patients who underwent orthotopic liver transplantation (OLT) in the time period between 1-1-2011 and 31-12-2013. The patients were divided into 2 groups: Group A with a MELD score 23 and Group B with a MELD score 23 and Group B those with MELD 23 (P ¼ .025, OR: 3.26, CI: 1.21e1.870) were found to be independent risk factors for patients mortality.
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7.31%, P ¼ .001) were higher in group A. The rate of graft dysfunction or rejection did not differ between the 2 groups. The duration of mechanical ventilation and stay in the ICU were prolonged in the group with the higher MELD score (P ¼ .013 and .009, respectively). Patients’ 30-day mortality was not statistically different between the 2 groups (P ¼ .420, Fig 1). However, it was found that renal replacement and infections had a statistically significant impact on mortality (P ¼ .004 and .22, respectively). There was a notable difference in 180-day survival between the 2 groups (87.5% vs 67.3%, P ¼ .040) (Fig 2). DISCUSSION
Fig 2. 180-days mortality.
Looking through the literature, we come across a constant search for the factors that influence mortality after OLT. The question of how grafts can be allocated in a better and more fair way always remains a current and crucial one. MELD score was introduced in Greece, as in every transplantation center worldwide, with the purpose of reducing mortality on the waiting list and a speedier transplantation. It has indeed contributed to the recognition of the most severe cases of hepatic failure and its application has facilitated the earlier and quicker graft allocation to those patients [19,20]. Additionally, as mentioned earlier, patients with HCC receive exceptional points (according to their tumor classification) due to the increased risk of tumor progression and/or metastatic disease [15]. It is accepted that a higher MELD score is related to higher mortality in chronic hepatic failure [6,7]. Hence, we could assume that a higher preoperative MELD score would correlate to a higher mortality and morbidity postoperatively. However, the effect of MELD score on mortality remains vague and unclear. MELD-based graft allocation has raised a lot of debate and contradictory studies can be found in the literature. Habib et al [10] concluded that patient and graft survival is directly related to the preoperative MELD score, while Knawal et al [21] supported that a 10-point increase in the preoperative MELD score resulted in a 39% increase in
mortality. Contrary to that, Ravaioli et al [22] did not find a correlation between the recipient’s preoperative MELD score and survival. Yoo et al [23] noted a worse outcome in patients with a MELD score >30. In this study we did not observe a difference in 30-day mortality between the 2 groups, but there was an evident statistical difference in mortality in 180 days. The patients with a higher MELD score required longer mechanical ventilation and stay in the ICU, more transfusions and higher hemodynamic support. These findings agree with those in the Ferraz-Neto et al study [24]. Readmissions and renal replacement therapy rates are higher in Group A. The 2 groups also differ in the preoperative serum creatinine levels. That is perhaps expected, given the fact that renal function, expressed by serum creatinine values, is included in the MELD score. The need for renal replacement therapy, however, is not dependent on preoperative creatinine levels only, but also on several other preoperative and postoperative factors. Perhaps this is why Cox-regression analysis shows that the preoperative level of creatinine is not a risk factor for mortality. Nevertheless, renal replacement is an independent risk factor, as well as a MELD score >23, hemodynamic instability and patients’ age (in our study though, there was not a significant difference between the 2 groups in terms of age). Moreover, Chuan et al [11] report a relation of short-term mortality with preoperative dialysis, massive transfusions and hyponatremia (especially in patients with high) MELD score, contrary to the findings in our study. As evident, a large part of the literature discusses the patient hospitalization costs which may increase in cases where there is a need for prolonged hospitalization or when complications occur [25]. There is a continuous effort to recognize the factors affecting post-transplantation mortality in order to evaluate how worthwhile liver transplantations can be. Conclusion
Fig 1. 30-day survival.
The patients’ sample used for the study presented in this paper could be considered as quite small. However, the results of the study are indicative due to the fact that there is only one liver transplantation center in Greece.
IMPACT OF MELD SCORE IN GREECE
So, our study concluded that the short-term mortality did not differ significantly between patients with high MELD score (MELD >23) and those with low MELD score. On the other hand, patients with higher MELD score needed a prolonged ICU stay while, statistically, they showed increased long-term mortality and morbidity. Moreover, this study identified MELD >23 as an independent risk factor for mortality. REFERENCES [1] Talwalkar JA, Seaberg E, Kim WR, Wiesner RH. Predicting clinical and economic outcomes after liver transplantation using the Mayo primary sclerosing cholangiitis model and Child-Pugh score. Liver Transpl 2000;6(6):753e8. [2] Liver recipient all ABO. UNOS/OPTN. http://www.optn.org/ latestdata/rptData.asp. 2009. [3] Coombes JM, Trotter JF. Development of the allocation system for deceased donor liver transplantation. Clin Med Res 2005;3(2):87e92. [4] Martin AP, Bartels M, Hauss J, Fangmann J. Overview of the MELD score and the UNOS adult liver allocation system. Transplant Proc 2007;39(10):3169e74. [5] Malinchoc M, Kamath PS, Gordon FD, et al. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology 2000;31(4):864e71. [6] Botta F, Giannini E, Romagnoli P, et al. MELD scoring system is useful for predicting prognosis in patients with liver cirrhosis and is correlated with residual liver function: a European study. Gut 2003;52(1):134e9. [7] Kamath PS, Wiesner RH, Malinchoc M, Kremers W, et al. A model to predict survival in patients with end-stage liver disease. Hepatology 2001;33(2):464e70. [8] Freeman RJ. Impact and benefits of the MELD scoring system for liver allocation. Transpl 2009;3:70e6. [9] Wiesner RH, McDiarmid SV, Kamath PS, et al. MELD and PELD: application of survival models to liver allocation. Liver Transpl 2001;7(7):567e80. [10] Habib S, Berk B, Chang CC, Demetris AJ, Fontes P, et al. MELD and prediction of post-liver transplantation survival. Liver Transpl 2006;12(3):440e7. [11] Chuan L, Wen TF, Yan LN, Li B, Yang JY, et al. Risk factors for in-hospital mortality of patients with high model for endstage liver disease scores following living donor liver transplantation. Ann Hepatol 2012;11(4):471e7. [12] Onaca NN, Levy MF, Netto GJ, Thomas MJ, et al. Pretransplant MELD score as a predictor of outcome after liver
3215 transplantation for chronic hepatitis C. Am J Transplant 2003;3(5): 626e30. [13] Nagler E, Van Vlierberghe H, Colle I, Troisi R, et al. Impact of MELD on short-term and long-term outcome following liver transplantation: a European perspective. Eur J Gastroenterol Hepatol 2005;17(8):849e56. [14] Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996;334(11): 693e9. [15] Northup PG, Berg CL. Hepatocellular carcinoma and model for end-stage liver disease exceptions: the more we understand, the more challenging the allocation gets. Liver Transpl 2012;18(4):381e3. [16] Pomfret EA, Washburn K, Wald C, Nalesnik MA, Douglas D, et al. Report of a national conference on liver allocation in patients with hepatocellular carcinoma in the United States. Liver Transpl 2010;16(3):262e78. http://dx.doi.org/10.1002/lt.21999. [17] Dutkowski P, Oberkofler CE, Béchir M, et al. The model for end-stage liver disease allocation system for liver transplantation saves lives, but increases morbidity and cost: a prospective outcome analysis. Liver Transpl 2011;17(6):674e84. [18] Saner FH, Sotiropoulos GC, Radtke A, Fouzas I, et al. Intensive care unit management of liver transplant patients: a formidable challenge for the intensivist. Transplant Proc 2008;40(9):3206e8. [19] Bernardi M, Gitto S, Biselli M. The MELD score in patients awaiting liver transplant: strengths and weaknesses. J Hepatol 2011;54(6):1297e306. [20] Cholongitas E, Marelli L, Shusang V, et al. A systematic review of the performance of the model for end-stage liver disease (MELD) in the setting of liver transplantation. Liver Transpl 2006;12(7):1049e61. [21] Kanwal F, Dulai GS, Spiegel BM, Yee HF, Gralnek IM. A comparison of liver transplantation outcomes in the pre- vs. postMELD eras. Aliment Pharmacol Ther 2005;21(2):169e77. [22] Ravaioli M, Grazi GL, Ballardini G, Cavrini G, et al. Liver transplantation with the Meld system: a prospective study from a single European center. Am J Transplant 2006;6(7):1572e7. [23] Yoo HY, Thuluvath PJ. Short-term post-liver transplant survival after the introduction of MELD scores for organ allocation in the United States. Liver Int 2005;25(3):536e41. [24] Ferraz-Neto BH, Zurstrassen MP, Hidalgo R, et al. Analysis of liver transplantation outcome in patients with MELD Score > or ¼ 30. Transplant Proc 2008;40(3):797e9. [25] Foxton MR, Al-Freah MA, Portal J, Sizer E, et al. Increased model for end-stage liver disease score at the time of liver transplant results in prolonged hospitalization and overall intensive care unit costs. Liver Transpl 2010;16(5):668e77.
ABSTRACT Introduction. The impact of preoperative Model for End-stage Liver Disease (MELD) score in postoperative mortality remains unclear. The assumption that patients with a higher MELD score will have a higher mortality rate is not confirmed and studies are contradictory. Aim. The study of the clinical course of patients with a higher MELD score and its impact in immediate and later mortality in comparison with patients with a lower MELD score in the only liver transplantation center in Greece. Method. We retrospectively studied 71 patients who underwent orthotopic liver transplantation (OLT) in the time period between 1-1-2011 and 31-12-2013. The patients were divided into 2 groups: Group A with a MELD score 23 and Group B with a MELD score 23 and Group B those with MELD 23 (P ¼ .025, OR: 3.26, CI: 1.21e1.870) were found to be independent risk factors for patients mortality.
3214
KARAPANAGIOTOU, KYDONA, DIMITRIADIS ET AL
7.31%, P ¼ .001) were higher in group A. The rate of graft dysfunction or rejection did not differ between the 2 groups. The duration of mechanical ventilation and stay in the ICU were prolonged in the group with the higher MELD score (P ¼ .013 and .009, respectively). Patients’ 30-day mortality was not statistically different between the 2 groups (P ¼ .420, Fig 1). However, it was found that renal replacement and infections had a statistically significant impact on mortality (P ¼ .004 and .22, respectively). There was a notable difference in 180-day survival between the 2 groups (87.5% vs 67.3%, P ¼ .040) (Fig 2). DISCUSSION
Fig 2. 180-days mortality.
Looking through the literature, we come across a constant search for the factors that influence mortality after OLT. The question of how grafts can be allocated in a better and more fair way always remains a current and crucial one. MELD score was introduced in Greece, as in every transplantation center worldwide, with the purpose of reducing mortality on the waiting list and a speedier transplantation. It has indeed contributed to the recognition of the most severe cases of hepatic failure and its application has facilitated the earlier and quicker graft allocation to those patients [19,20]. Additionally, as mentioned earlier, patients with HCC receive exceptional points (according to their tumor classification) due to the increased risk of tumor progression and/or metastatic disease [15]. It is accepted that a higher MELD score is related to higher mortality in chronic hepatic failure [6,7]. Hence, we could assume that a higher preoperative MELD score would correlate to a higher mortality and morbidity postoperatively. However, the effect of MELD score on mortality remains vague and unclear. MELD-based graft allocation has raised a lot of debate and contradictory studies can be found in the literature. Habib et al [10] concluded that patient and graft survival is directly related to the preoperative MELD score, while Knawal et al [21] supported that a 10-point increase in the preoperative MELD score resulted in a 39% increase in
mortality. Contrary to that, Ravaioli et al [22] did not find a correlation between the recipient’s preoperative MELD score and survival. Yoo et al [23] noted a worse outcome in patients with a MELD score >30. In this study we did not observe a difference in 30-day mortality between the 2 groups, but there was an evident statistical difference in mortality in 180 days. The patients with a higher MELD score required longer mechanical ventilation and stay in the ICU, more transfusions and higher hemodynamic support. These findings agree with those in the Ferraz-Neto et al study [24]. Readmissions and renal replacement therapy rates are higher in Group A. The 2 groups also differ in the preoperative serum creatinine levels. That is perhaps expected, given the fact that renal function, expressed by serum creatinine values, is included in the MELD score. The need for renal replacement therapy, however, is not dependent on preoperative creatinine levels only, but also on several other preoperative and postoperative factors. Perhaps this is why Cox-regression analysis shows that the preoperative level of creatinine is not a risk factor for mortality. Nevertheless, renal replacement is an independent risk factor, as well as a MELD score >23, hemodynamic instability and patients’ age (in our study though, there was not a significant difference between the 2 groups in terms of age). Moreover, Chuan et al [11] report a relation of short-term mortality with preoperative dialysis, massive transfusions and hyponatremia (especially in patients with high) MELD score, contrary to the findings in our study. As evident, a large part of the literature discusses the patient hospitalization costs which may increase in cases where there is a need for prolonged hospitalization or when complications occur [25]. There is a continuous effort to recognize the factors affecting post-transplantation mortality in order to evaluate how worthwhile liver transplantations can be. Conclusion
Fig 1. 30-day survival.
The patients’ sample used for the study presented in this paper could be considered as quite small. However, the results of the study are indicative due to the fact that there is only one liver transplantation center in Greece.
IMPACT OF MELD SCORE IN GREECE
So, our study concluded that the short-term mortality did not differ significantly between patients with high MELD score (MELD >23) and those with low MELD score. On the other hand, patients with higher MELD score needed a prolonged ICU stay while, statistically, they showed increased long-term mortality and morbidity. Moreover, this study identified MELD >23 as an independent risk factor for mortality. REFERENCES [1] Talwalkar JA, Seaberg E, Kim WR, Wiesner RH. Predicting clinical and economic outcomes after liver transplantation using the Mayo primary sclerosing cholangiitis model and Child-Pugh score. Liver Transpl 2000;6(6):753e8. [2] Liver recipient all ABO. UNOS/OPTN. http://www.optn.org/ latestdata/rptData.asp. 2009. [3] Coombes JM, Trotter JF. Development of the allocation system for deceased donor liver transplantation. Clin Med Res 2005;3(2):87e92. [4] Martin AP, Bartels M, Hauss J, Fangmann J. Overview of the MELD score and the UNOS adult liver allocation system. Transplant Proc 2007;39(10):3169e74. [5] Malinchoc M, Kamath PS, Gordon FD, et al. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology 2000;31(4):864e71. [6] Botta F, Giannini E, Romagnoli P, et al. MELD scoring system is useful for predicting prognosis in patients with liver cirrhosis and is correlated with residual liver function: a European study. Gut 2003;52(1):134e9. [7] Kamath PS, Wiesner RH, Malinchoc M, Kremers W, et al. A model to predict survival in patients with end-stage liver disease. Hepatology 2001;33(2):464e70. [8] Freeman RJ. Impact and benefits of the MELD scoring system for liver allocation. Transpl 2009;3:70e6. [9] Wiesner RH, McDiarmid SV, Kamath PS, et al. MELD and PELD: application of survival models to liver allocation. Liver Transpl 2001;7(7):567e80. [10] Habib S, Berk B, Chang CC, Demetris AJ, Fontes P, et al. MELD and prediction of post-liver transplantation survival. Liver Transpl 2006;12(3):440e7. [11] Chuan L, Wen TF, Yan LN, Li B, Yang JY, et al. Risk factors for in-hospital mortality of patients with high model for endstage liver disease scores following living donor liver transplantation. Ann Hepatol 2012;11(4):471e7. [12] Onaca NN, Levy MF, Netto GJ, Thomas MJ, et al. Pretransplant MELD score as a predictor of outcome after liver
3215 transplantation for chronic hepatitis C. Am J Transplant 2003;3(5): 626e30. [13] Nagler E, Van Vlierberghe H, Colle I, Troisi R, et al. Impact of MELD on short-term and long-term outcome following liver transplantation: a European perspective. Eur J Gastroenterol Hepatol 2005;17(8):849e56. [14] Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996;334(11): 693e9. [15] Northup PG, Berg CL. Hepatocellular carcinoma and model for end-stage liver disease exceptions: the more we understand, the more challenging the allocation gets. Liver Transpl 2012;18(4):381e3. [16] Pomfret EA, Washburn K, Wald C, Nalesnik MA, Douglas D, et al. Report of a national conference on liver allocation in patients with hepatocellular carcinoma in the United States. Liver Transpl 2010;16(3):262e78. http://dx.doi.org/10.1002/lt.21999. [17] Dutkowski P, Oberkofler CE, Béchir M, et al. The model for end-stage liver disease allocation system for liver transplantation saves lives, but increases morbidity and cost: a prospective outcome analysis. Liver Transpl 2011;17(6):674e84. [18] Saner FH, Sotiropoulos GC, Radtke A, Fouzas I, et al. Intensive care unit management of liver transplant patients: a formidable challenge for the intensivist. Transplant Proc 2008;40(9):3206e8. [19] Bernardi M, Gitto S, Biselli M. The MELD score in patients awaiting liver transplant: strengths and weaknesses. J Hepatol 2011;54(6):1297e306. [20] Cholongitas E, Marelli L, Shusang V, et al. A systematic review of the performance of the model for end-stage liver disease (MELD) in the setting of liver transplantation. Liver Transpl 2006;12(7):1049e61. [21] Kanwal F, Dulai GS, Spiegel BM, Yee HF, Gralnek IM. A comparison of liver transplantation outcomes in the pre- vs. postMELD eras. Aliment Pharmacol Ther 2005;21(2):169e77. [22] Ravaioli M, Grazi GL, Ballardini G, Cavrini G, et al. Liver transplantation with the Meld system: a prospective study from a single European center. Am J Transplant 2006;6(7):1572e7. [23] Yoo HY, Thuluvath PJ. Short-term post-liver transplant survival after the introduction of MELD scores for organ allocation in the United States. Liver Int 2005;25(3):536e41. [24] Ferraz-Neto BH, Zurstrassen MP, Hidalgo R, et al. Analysis of liver transplantation outcome in patients with MELD Score > or ¼ 30. Transplant Proc 2008;40(3):797e9. [25] Foxton MR, Al-Freah MA, Portal J, Sizer E, et al. Increased model for end-stage liver disease score at the time of liver transplant results in prolonged hospitalization and overall intensive care unit costs. Liver Transpl 2010;16(5):668e77.
