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Higher Graft-to-Host Ratio May Decrease Posttransplant Mortality in Patients With a High MELD Score
Higher Graft-to-Host Ratio May Decrease Posttransplant Mortality in Patients With a High MELD Score R. Emiroglu, U. Yilmaz, M. Coskun, H. Karakayali, and M. Haberal ABSTRACT The aim of this study was to determine whether scores from the model for end-stage liver disease (MELD) can be used in the preoperative strategic planning of transplantation surgery. We retrospectively analyzed the outcomes of 62 adult liver transplantation patients whose operation was performed at our center between January 2001 and June 2006. All patients had MELD scores between 8 and 35 with an average value of 20. We compared postoperative mortality among patients who had MELD scores higher than 20 as determined by their graft-to-host ratios. We separately grouped the patients whose graft-to-body weight ratio (GBWR) was equal to or lower than 1 and whose GBWR was higher than 1. The GBWRs associated with mortality after living-donor liver transplantation in the early postoperative period were considered significant (P ⫽ .005). MELD scores were also found to be associated with mortality (P ⫽ .006). Mortality rates in patients with high MELD scores and a low GBWR were highest among the other combinations. In conclusion, we found that GBWR lower than 1 and MELD score higher than 20 are significant risk factors for mortality after living donor liver transplantation. Patients with low MELD scores can undergo transplantation when their GBWR is lower than 1, but recipients with high MELD scores should receive grafts only when their GBWR is higher than 1.
T
HE MODEL for end-stage liver disease (MELD) is a mathematical model in which the serum bilirubin and creatinine levels and the international normalized ratio (INR) for prothrombin time are used to accurately predict short-term survival in patients awaiting liver transplantation (LT).1 Although the MELD score has been an excellent predictor of 3-month mortality in cirrhotic patients awaiting LT, its prognostic accuracy in patients who have undergone LT is unknown.2 The aim of this study was to evaluate whether the preoperative MELD score predicted early mortality after LT. We also compared the postoperative mortality rate in patients with MELD scores higher than 20 that were based on their graft-to-host ratio (GBWR).
study participants were divided into two groups according to MELD score: group 1 (MELD score of ⬍20) and group 2 (MELD score of ⱖ 20). Those two groups were divided into two subgroups: patients with a GBWR of ⱕ1 and those with a GBWR of ⬎1. All patients received our previously reported immunosuppressive and management protocol,3,4 and none received induction immunosuppressive therapy. Statistical analysis was performed with the chisquare and Fisher Exact Tests.
RESULTS
PATIENTS AND METHODS
The study group consisted of 62 patients (50 men and 12 women; mean age, 43.1 ⫾ 12.9 years; age range, 18 – 64 years). Immediately before transplantation, the MELD scores were less than 20 in 37 patients (59.6%) and higher than 20 in 25 patients (41.4%). The medical reasons that
We performed 132 liver transplantations between September 20, 2001 and June 29, 2006. We excluded patients younger than 17 years, those who had undergone retransplantation, and those who underwent transplantation for acute liver failure. The final study group consisted of 62 patients who were analyzed retrospectively. We used the UNOS formula of immediate pretransplantation parameters to calculate the MELD score. All patients had MELD scores between 8 and 35 and an average MELD value of 20. The
From the Departments of General Surgery and Transplantation (R.E., H.K., M.H.), Gastroenterology (U.Y.), and Radiology (M.C.), Baskent University Faculty of Medicine, Ankara, Turkey. Address reprint requests to Mehmet Haberal, MD, FACS, FICS (Hon), Baskent Universitesi Rektorluk, 1. Cad. No: 77 Kat:4 Bahcelievler, 06490, Ankara, Turkey. E-mail: rektorluk@baskent-ank. edu.tr
0041-1345/07/$–see front matter doi:10.1016/j.transproceed.2007.02.048
© 2007 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1164
Transplantation Proceedings, 39, 1164 –1165 (2007)
MORTALITY IN PATIENTS WITH HIGH MELD SCORE
1165
necessitated LT were similar in both groups, and the most common indication for LT was viral hepatitis (59%). Twenty of the 62 patients had received a graft from a cadaveric donor, and 40 had received their graft from a living donor. In group I, the GBWRs were higher than 1 in 32 patients and equal to or lower than 1 in 5 patients. In group 2, the GBWRs were higher than 1 in 16 patients and equal to or lower than 1 in 9 patients. Hepatic arterial thrombosis developed in three patients in group 1 and in two patients in group 2. Biliary complications were experienced by six patients in group 1 (a biliary leak in five and biliary stenosis in one) and by five patients in group 2 (a biliary leak in three and biliary stenosis in two). The incidence of hepatic arterial thrombosis and biliary complications in the two groups was not significant. Acute renal insufficiency developed in seven patients (three in group 1 and four in group 2) during the early postoperative period. The incidence of renal insufficiency was similar in both groups. Renal function was recovered in all patients. Eight patients died during the early postoperative period. One (3%) of those eight patients was in group 1, and seven (25%) were in group 2. MELD scores were associated with mortality (P ⫽ .006). Death occurred in the early postoperative period in seven patients in group 2. Four (44%) of those seven patients had a GBWR equal or lower than 1, and three (17%) had a GBWR higher than 1. GBWR was also significantly associated with mortality after LT (P ⫽ .005). The mortality rate in the study subjects is summarized in Table 1. Mortality rates in patients with high MELD scores and a low GBWR were highest among the other combinations. The causes of death included sepsis in six patients, adult respiratory distress syndrome in one, and pulmonary hypertension in one. DISCUSSION
The MELD score has emerged as a tool that is useful in the estimation of mortality in patients awaiting liver transplantation.5–7 Using the MELD is advantageous because its score is based on only three objective and rapidly available standardized biochemical assessments. A number of recent studies performed in the United States have demonstrated that the MELD score obtained immediately before transplantation is associated with posttransplant patient survival. Patients with high MELD scores have a poorer posttransplant survival rate.8,9 However, Adler and colleagues did not find the MELD score to be predictive of transplant Table 1. Mortality Rates in the Study Subjects MELD
MELD ⬍ 20 37 patients MELD ⱖ 20 25 patients
GBWR
GBWR GBWR GBWR GBWR
⬎ ⱕ ⬎ ⱕ
1 1 1 1
Patient No. (%)
Mortality
Rate (%)
32 (51) 5 (8) 16 (26.5) 9 (14.5)
1 0 3 4
3 0 17 44
MELD, Model for end-stage liver disease; GBWR, graft to body weight ratio.
patients survival.10 Our findings, which contradicted those of Adler and colleagues10 but were consistent with the results of other investigators,8,9 showed that pretransplantation MELD scores were closely correlated with survival in the first month after transplantation. The GBWR has been used to assess the graft size of a potential donor, and GBWR values of less than 0.8% have been associated with increased posttransplantation mortality and morbidity.11–13 We prefer to transplant a graft from a donor with a GBWR greater than 0.8%. In our study, 14 patients (22.5%) had a GBWR of less than 1. The MELD score was less than 20 in five of those 14 patients, none of whom died during the study period, but five of the nine patients who had a MELD score higher than 20 did die during that time. We concluded that a GBWR lower than 1 and MELD scores higher than 20 are significant risk factors for mortality after living-donor liver transplantation. Patients with low MELD scores can undergo transplantation when their GBWR is lower than 1, but patients with high MELD scores should receive grafts from donors with a GBWR higher than 1.
REFERENCES 1. Kamath PS, Wiesner RH, Malinchoc M, et al: A model to predict survival in patients with end-stage liver disease. Hepatology 33:464, 2001 2. Merion RM: When is a patient too well and when is a patient too sick for a liver transplant? Liver Transpl 10:S69, 2004 3. Moray G, Boyvat F, Sevmis S, et al: Vascular complications after liver transplantation in pediatric patients. Transplant Proc 37:3200, 2005 4. Dalgic A, Ozcay F, Arslan G, et al: Living-related liver transplantation in pediatric patients. Transplant Proc 37:3133, 2005 5. Pagliaro L: MELD: the end of Child-Pugh classification? J Hepatol 36:141, 2002 6. Wiesner RH, McDiarmid SV, Kamath PS, et al: MELD and PELD: application of survival models to liver allocation. Liver Transpl 7:567, 2001 7. McCaughan GW, Strasser SI: To MELD or not to MELD? Hepatology 34:215, 2001 8. Desai NM, Mange KC, Crawford MD, et al: Predicting outcome after liver transplantation: utility of the model for endstage liver disease and a newly derived discrimination function. Transplantation 77:99, 2004 9. Onaca NN, Levy MF, Sanchez EQ, et al: A correlation between the pretransplantation MELD score and mortality in the first two years after liver transplantation. Liver Transpl 9:117, 2003 10. Adler M, De Gendt E, Vereerstraeten P, et al: Value of the MELD score for the assessment of pre- and post-liver transplantation survival. Transplant Proc 37:2863, 2005 11. Kamel IR, Kruskal JB, Warmbrand G, et al: Accuracy of volumetric measurements after virtual right hepatectomy in potential donors undergoing living adult liver transplantation. Am J Roentgenol 176:483, 2001 12. Lo CM: Complications and long-term outcome of living liver donors: a survey of 1,508 cases in five Asian centers. Transplantation 75:S12, 2003 13. Ueda M, Oike F, Ogura Y, et al: Long-term outcomes of 600 living donor liver transplants for pediatric patients at a single center. Liver Transpl 12:1326, 2006
T
HE MODEL for end-stage liver disease (MELD) is a mathematical model in which the serum bilirubin and creatinine levels and the international normalized ratio (INR) for prothrombin time are used to accurately predict short-term survival in patients awaiting liver transplantation (LT).1 Although the MELD score has been an excellent predictor of 3-month mortality in cirrhotic patients awaiting LT, its prognostic accuracy in patients who have undergone LT is unknown.2 The aim of this study was to evaluate whether the preoperative MELD score predicted early mortality after LT. We also compared the postoperative mortality rate in patients with MELD scores higher than 20 that were based on their graft-to-host ratio (GBWR).
study participants were divided into two groups according to MELD score: group 1 (MELD score of ⬍20) and group 2 (MELD score of ⱖ 20). Those two groups were divided into two subgroups: patients with a GBWR of ⱕ1 and those with a GBWR of ⬎1. All patients received our previously reported immunosuppressive and management protocol,3,4 and none received induction immunosuppressive therapy. Statistical analysis was performed with the chisquare and Fisher Exact Tests.
RESULTS
PATIENTS AND METHODS
The study group consisted of 62 patients (50 men and 12 women; mean age, 43.1 ⫾ 12.9 years; age range, 18 – 64 years). Immediately before transplantation, the MELD scores were less than 20 in 37 patients (59.6%) and higher than 20 in 25 patients (41.4%). The medical reasons that
We performed 132 liver transplantations between September 20, 2001 and June 29, 2006. We excluded patients younger than 17 years, those who had undergone retransplantation, and those who underwent transplantation for acute liver failure. The final study group consisted of 62 patients who were analyzed retrospectively. We used the UNOS formula of immediate pretransplantation parameters to calculate the MELD score. All patients had MELD scores between 8 and 35 and an average MELD value of 20. The
From the Departments of General Surgery and Transplantation (R.E., H.K., M.H.), Gastroenterology (U.Y.), and Radiology (M.C.), Baskent University Faculty of Medicine, Ankara, Turkey. Address reprint requests to Mehmet Haberal, MD, FACS, FICS (Hon), Baskent Universitesi Rektorluk, 1. Cad. No: 77 Kat:4 Bahcelievler, 06490, Ankara, Turkey. E-mail: rektorluk@baskent-ank. edu.tr
0041-1345/07/$–see front matter doi:10.1016/j.transproceed.2007.02.048
© 2007 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1164
Transplantation Proceedings, 39, 1164 –1165 (2007)
MORTALITY IN PATIENTS WITH HIGH MELD SCORE
1165
necessitated LT were similar in both groups, and the most common indication for LT was viral hepatitis (59%). Twenty of the 62 patients had received a graft from a cadaveric donor, and 40 had received their graft from a living donor. In group I, the GBWRs were higher than 1 in 32 patients and equal to or lower than 1 in 5 patients. In group 2, the GBWRs were higher than 1 in 16 patients and equal to or lower than 1 in 9 patients. Hepatic arterial thrombosis developed in three patients in group 1 and in two patients in group 2. Biliary complications were experienced by six patients in group 1 (a biliary leak in five and biliary stenosis in one) and by five patients in group 2 (a biliary leak in three and biliary stenosis in two). The incidence of hepatic arterial thrombosis and biliary complications in the two groups was not significant. Acute renal insufficiency developed in seven patients (three in group 1 and four in group 2) during the early postoperative period. The incidence of renal insufficiency was similar in both groups. Renal function was recovered in all patients. Eight patients died during the early postoperative period. One (3%) of those eight patients was in group 1, and seven (25%) were in group 2. MELD scores were associated with mortality (P ⫽ .006). Death occurred in the early postoperative period in seven patients in group 2. Four (44%) of those seven patients had a GBWR equal or lower than 1, and three (17%) had a GBWR higher than 1. GBWR was also significantly associated with mortality after LT (P ⫽ .005). The mortality rate in the study subjects is summarized in Table 1. Mortality rates in patients with high MELD scores and a low GBWR were highest among the other combinations. The causes of death included sepsis in six patients, adult respiratory distress syndrome in one, and pulmonary hypertension in one. DISCUSSION
The MELD score has emerged as a tool that is useful in the estimation of mortality in patients awaiting liver transplantation.5–7 Using the MELD is advantageous because its score is based on only three objective and rapidly available standardized biochemical assessments. A number of recent studies performed in the United States have demonstrated that the MELD score obtained immediately before transplantation is associated with posttransplant patient survival. Patients with high MELD scores have a poorer posttransplant survival rate.8,9 However, Adler and colleagues did not find the MELD score to be predictive of transplant Table 1. Mortality Rates in the Study Subjects MELD
MELD ⬍ 20 37 patients MELD ⱖ 20 25 patients
GBWR
GBWR GBWR GBWR GBWR
⬎ ⱕ ⬎ ⱕ
1 1 1 1
Patient No. (%)
Mortality
Rate (%)
32 (51) 5 (8) 16 (26.5) 9 (14.5)
1 0 3 4
3 0 17 44
MELD, Model for end-stage liver disease; GBWR, graft to body weight ratio.
patients survival.10 Our findings, which contradicted those of Adler and colleagues10 but were consistent with the results of other investigators,8,9 showed that pretransplantation MELD scores were closely correlated with survival in the first month after transplantation. The GBWR has been used to assess the graft size of a potential donor, and GBWR values of less than 0.8% have been associated with increased posttransplantation mortality and morbidity.11–13 We prefer to transplant a graft from a donor with a GBWR greater than 0.8%. In our study, 14 patients (22.5%) had a GBWR of less than 1. The MELD score was less than 20 in five of those 14 patients, none of whom died during the study period, but five of the nine patients who had a MELD score higher than 20 did die during that time. We concluded that a GBWR lower than 1 and MELD scores higher than 20 are significant risk factors for mortality after living-donor liver transplantation. Patients with low MELD scores can undergo transplantation when their GBWR is lower than 1, but patients with high MELD scores should receive grafts from donors with a GBWR higher than 1.
REFERENCES 1. Kamath PS, Wiesner RH, Malinchoc M, et al: A model to predict survival in patients with end-stage liver disease. Hepatology 33:464, 2001 2. Merion RM: When is a patient too well and when is a patient too sick for a liver transplant? Liver Transpl 10:S69, 2004 3. Moray G, Boyvat F, Sevmis S, et al: Vascular complications after liver transplantation in pediatric patients. Transplant Proc 37:3200, 2005 4. Dalgic A, Ozcay F, Arslan G, et al: Living-related liver transplantation in pediatric patients. Transplant Proc 37:3133, 2005 5. Pagliaro L: MELD: the end of Child-Pugh classification? J Hepatol 36:141, 2002 6. Wiesner RH, McDiarmid SV, Kamath PS, et al: MELD and PELD: application of survival models to liver allocation. Liver Transpl 7:567, 2001 7. McCaughan GW, Strasser SI: To MELD or not to MELD? Hepatology 34:215, 2001 8. Desai NM, Mange KC, Crawford MD, et al: Predicting outcome after liver transplantation: utility of the model for endstage liver disease and a newly derived discrimination function. Transplantation 77:99, 2004 9. Onaca NN, Levy MF, Sanchez EQ, et al: A correlation between the pretransplantation MELD score and mortality in the first two years after liver transplantation. Liver Transpl 9:117, 2003 10. Adler M, De Gendt E, Vereerstraeten P, et al: Value of the MELD score for the assessment of pre- and post-liver transplantation survival. Transplant Proc 37:2863, 2005 11. Kamel IR, Kruskal JB, Warmbrand G, et al: Accuracy of volumetric measurements after virtual right hepatectomy in potential donors undergoing living adult liver transplantation. Am J Roentgenol 176:483, 2001 12. Lo CM: Complications and long-term outcome of living liver donors: a survey of 1,508 cases in five Asian centers. Transplantation 75:S12, 2003 13. Ueda M, Oike F, Ogura Y, et al: Long-term outcomes of 600 living donor liver transplants for pediatric patients at a single center. Liver Transpl 12:1326, 2006