LIVER TRANSPLANTATION 21:1331–1332, 2015
LETTERS TO THE EDITOR
Liver Transplantation in Patients With End-Stage Liver Disease Requiring Intensive Care Unit Admission and Intubation Received May 18, 2015; accepted May 26, 2015.
TO THE EDITOR: We read with interest the study by Knaak et al.1 recently published in Liver Transplantation, regarding the outcome and the risk factors predicting outcomes
in intensive care unit (ICU)–dependent end-stage liver disease patients who underwent liver transplantation (LT). This study is in accordance with several others which assessed the outcome after LT in critically ill patients2 or in the sickest patients (Model for
Figure 1. Comparison of the area under the receiver operating characteristic (AUROC) curves estimated for each score in 350 patients with cirrhosis who underwent LT. (A) Child-Pugh, University of California Los Angeles–Framingham Risk Score (UCLA-FRS), Model for End-Stage Liver Disease (MELD) score, donor age-MELD (D-MELD), donor risk index (DRI)–MELD and for (B) CLIF-SOFA, CLIF - Consortium Organ Failure score (CLIF-OF), Sequential Organ Failure Assessment (SOFA), CLIF - Consortium Acute Decompensation (CLIF-AD) scores.
Grants or funding support: Nothing to report. Address reprint requests to Eric Levesque, M.D., Department of Anaesthesia and Surgical Intensive Care, Liver Intensive Care Unit, AP-HP, ^pital Henri Mondor, 51 Avenue du Mare chal de Lattre de Tassigny, 94010 Cre teil, France. Telephone: 00-33-1-49-81-21-11/36449; FAX: Ho 00-33-1-45-17-80-18; E-mail: [email protected] DOI 10.1002/lt.24201 View this article online at wileyonlinelibrary.com. LIVER TRANSPLANTATION. DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases C 2015 American Association for the Study of Liver Diseases. V
1332 LETTERS TO THE EDITOR
End-Stage Liver Disease [MELD] > 40),3 and it shows that LT in these subgroups of patients achieved acceptable long-term graft and patient survival rates. However, the authors fail to identify risk factors predicting poor outcomes in this cohort. A selection bias inherent to the study design is to be taken into account. Cannot a stringent patient selection have resulted in a major improvement of shortand long-term survival? It might be informative to know the reasons for endotracheal intubation and mechanical ventilation as well as the criteria for hospitalization in the ICU. Moreover, during the study period, how many patients requiring mechanical ventilation before LT were listed for transplant, and among them, how many were finally transplanted? How many were not transplanted and for which reasons? We believe, as do the authors, that a careful selection of transplantation candidates in this situation is the key of management because the wait-list mortality is high, the time of transplantation is crucial, and the window of opportunity is small. In addition, as shown by other authors, prognostic scores such as the Sequential Organ Failure Assessment (SOFA) score or MELD score (used in this study) do not help us to identify the time and the good candidates for LT because they poorly predict 90-day survival after LT in critically ill patients with cirrhosis.4,5 To add to their evaluation, we report our experience in 350 patients with cirrhosis who were consecutively transplanted in our institution between January 2008 and December 2013. At the time of LT, in our cohort, 52 patients were hospitalized in the ICU, and 29 patients required mechanical ventilation. Thirty-seven patients (10.6%) died during the 3 months after LT. To identify which score had the best discrimination capacity to predict outcome after LT in patients with cirrhosis, areas under the receiver operating characteristic curve (AUROC) were compared (Fig. 1). Similar to the study evaluating the outcome in the ICU of patients with cirrhosis,6 we found that liver function was not the main determinant of outcome so that an organ failure score as the SOFA or the new chronic liver failure (CLIF)–SOFA score7 could be more useful in predicting outcome, although not sufficient. As long as the posttransplant mortality risk is lower than the mortality risk on the waiting list (particularly in patients with cirrhosis requiring mechanical ventilation),8 this prioritization of the sickest patients increases the efficiency of LT. In agreement with the authors, we are convinced that LT in patients with cirrhosis requiring mechanical ventilation is feasible and is associated with good outcome. However, a strict selection of these patients is essential in this organ shortage period to be able to identify the patients with cirrhosis who will maximally benefit from LT. This selection should include the recipient’s
LIVER TRANSPLANTATION, October 2015
parameters (organ failures, cardiac risk evaluation, pretransplant sepsis, etc.) for inclusion on the waiting list but also the donor’s parameters (missing in this study) for the decision of transplantation. Eric Levesque, M.D.1 Moez Khemiss, M.D.1 Zaid Noorah, M.D.1 Cyrille Feray, M.D., Ph.D.2 Daniel Azoulay, M.D., Ph.D.3 Gilles Dhonneur, M.D., Ph.D.1 1 Department of Anaesthesia and Surgical Intensive Care Liver Intensive Care Unit ^ pital Henri Mondor AP-HP, Ho teil, France Cre 2 Department of Hepatology ^ pital Henri Mondor AP-HP, Ho teil, France Cre 3 Digestive Surgery and Liver Transplant Unit ^ pital Henri Mondor AP-HP, Ho teil, France Cre
REFERENCES 1. Knaak J, McVey M, Bazerbachi F, Goldaracena N, Spetzler V, Selzner N, et al. Liver transplantation in patients with end-stage liver disease requiring intensive care unit admission and intubation. Liver Transpl 2015; 21:761-767. 2. Umgelter A, Lange K, Kornberg A, B€ uchler P, Friess H, Schmid RM. Orthotopic liver transplantation in critically ill cirrhotic patients with multi-organ failure: a singlecenter experience. Transplant Proc 2011;43:3762-3768. 3. Petrowsky H, Rana A, Kaldas FM, Sharma A, Hong JC, Agopian VG, et al. Liver transplantation in highest acuity recipients: identifying factors to avoid futility. Ann Surg 2014;259:1186-1194. 4. Karvellas CJ, Lescot T, Goldberg P, Sharpe MD, Ronco JJ, Renner EL, et al. Liver transplantation in the critically ill: a multicenter Canadian retrospective cohort study. Crit Care 2013;17:R28. 5. Brown RS Jr, Kumar KS, Russo MW, Kinkhabwala M, Rudow DL, Harren P, et al. Model for end-stage liver disease and Child-Turcotte-Pugh score as predictors of pretransplantation disease severity, posttransplantation outcome, and resource utilization in United Network for Organ Sharing status 2A patients. Liver Transpl 2002;8:278-284. 6. Levesque E, Hoti E, Azoulay D, Icha€ı P, Habouchi H, Castaing D, et al. Prospective evaluation of the prognostic scores for cirrhotic patients admitted to an intensive care unit. J Hepatol 2012;56:95-102. 7. Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, et al.; for CANONIC Study Investigators of the EASL– CLIF Consortium. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 2013;144: 1426-1437. 8. Levesque E, Saliba F, Icha€ı P, Samuel D. Outcome of patients with cirrhosis requiring mechanical ventilation in ICU. J Hepatol 2014;60:570-578.
LETTERS TO THE EDITOR
Liver Transplantation in Patients With End-Stage Liver Disease Requiring Intensive Care Unit Admission and Intubation Received May 18, 2015; accepted May 26, 2015.
TO THE EDITOR: We read with interest the study by Knaak et al.1 recently published in Liver Transplantation, regarding the outcome and the risk factors predicting outcomes
in intensive care unit (ICU)–dependent end-stage liver disease patients who underwent liver transplantation (LT). This study is in accordance with several others which assessed the outcome after LT in critically ill patients2 or in the sickest patients (Model for
Figure 1. Comparison of the area under the receiver operating characteristic (AUROC) curves estimated for each score in 350 patients with cirrhosis who underwent LT. (A) Child-Pugh, University of California Los Angeles–Framingham Risk Score (UCLA-FRS), Model for End-Stage Liver Disease (MELD) score, donor age-MELD (D-MELD), donor risk index (DRI)–MELD and for (B) CLIF-SOFA, CLIF - Consortium Organ Failure score (CLIF-OF), Sequential Organ Failure Assessment (SOFA), CLIF - Consortium Acute Decompensation (CLIF-AD) scores.
Grants or funding support: Nothing to report. Address reprint requests to Eric Levesque, M.D., Department of Anaesthesia and Surgical Intensive Care, Liver Intensive Care Unit, AP-HP, ^pital Henri Mondor, 51 Avenue du Mare chal de Lattre de Tassigny, 94010 Cre teil, France. Telephone: 00-33-1-49-81-21-11/36449; FAX: Ho 00-33-1-45-17-80-18; E-mail: [email protected] DOI 10.1002/lt.24201 View this article online at wileyonlinelibrary.com. LIVER TRANSPLANTATION. DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases C 2015 American Association for the Study of Liver Diseases. V
1332 LETTERS TO THE EDITOR
End-Stage Liver Disease [MELD] > 40),3 and it shows that LT in these subgroups of patients achieved acceptable long-term graft and patient survival rates. However, the authors fail to identify risk factors predicting poor outcomes in this cohort. A selection bias inherent to the study design is to be taken into account. Cannot a stringent patient selection have resulted in a major improvement of shortand long-term survival? It might be informative to know the reasons for endotracheal intubation and mechanical ventilation as well as the criteria for hospitalization in the ICU. Moreover, during the study period, how many patients requiring mechanical ventilation before LT were listed for transplant, and among them, how many were finally transplanted? How many were not transplanted and for which reasons? We believe, as do the authors, that a careful selection of transplantation candidates in this situation is the key of management because the wait-list mortality is high, the time of transplantation is crucial, and the window of opportunity is small. In addition, as shown by other authors, prognostic scores such as the Sequential Organ Failure Assessment (SOFA) score or MELD score (used in this study) do not help us to identify the time and the good candidates for LT because they poorly predict 90-day survival after LT in critically ill patients with cirrhosis.4,5 To add to their evaluation, we report our experience in 350 patients with cirrhosis who were consecutively transplanted in our institution between January 2008 and December 2013. At the time of LT, in our cohort, 52 patients were hospitalized in the ICU, and 29 patients required mechanical ventilation. Thirty-seven patients (10.6%) died during the 3 months after LT. To identify which score had the best discrimination capacity to predict outcome after LT in patients with cirrhosis, areas under the receiver operating characteristic curve (AUROC) were compared (Fig. 1). Similar to the study evaluating the outcome in the ICU of patients with cirrhosis,6 we found that liver function was not the main determinant of outcome so that an organ failure score as the SOFA or the new chronic liver failure (CLIF)–SOFA score7 could be more useful in predicting outcome, although not sufficient. As long as the posttransplant mortality risk is lower than the mortality risk on the waiting list (particularly in patients with cirrhosis requiring mechanical ventilation),8 this prioritization of the sickest patients increases the efficiency of LT. In agreement with the authors, we are convinced that LT in patients with cirrhosis requiring mechanical ventilation is feasible and is associated with good outcome. However, a strict selection of these patients is essential in this organ shortage period to be able to identify the patients with cirrhosis who will maximally benefit from LT. This selection should include the recipient’s
LIVER TRANSPLANTATION, October 2015
parameters (organ failures, cardiac risk evaluation, pretransplant sepsis, etc.) for inclusion on the waiting list but also the donor’s parameters (missing in this study) for the decision of transplantation. Eric Levesque, M.D.1 Moez Khemiss, M.D.1 Zaid Noorah, M.D.1 Cyrille Feray, M.D., Ph.D.2 Daniel Azoulay, M.D., Ph.D.3 Gilles Dhonneur, M.D., Ph.D.1 1 Department of Anaesthesia and Surgical Intensive Care Liver Intensive Care Unit ^ pital Henri Mondor AP-HP, Ho teil, France Cre 2 Department of Hepatology ^ pital Henri Mondor AP-HP, Ho teil, France Cre 3 Digestive Surgery and Liver Transplant Unit ^ pital Henri Mondor AP-HP, Ho teil, France Cre
REFERENCES 1. Knaak J, McVey M, Bazerbachi F, Goldaracena N, Spetzler V, Selzner N, et al. Liver transplantation in patients with end-stage liver disease requiring intensive care unit admission and intubation. Liver Transpl 2015; 21:761-767. 2. Umgelter A, Lange K, Kornberg A, B€ uchler P, Friess H, Schmid RM. Orthotopic liver transplantation in critically ill cirrhotic patients with multi-organ failure: a singlecenter experience. Transplant Proc 2011;43:3762-3768. 3. Petrowsky H, Rana A, Kaldas FM, Sharma A, Hong JC, Agopian VG, et al. Liver transplantation in highest acuity recipients: identifying factors to avoid futility. Ann Surg 2014;259:1186-1194. 4. Karvellas CJ, Lescot T, Goldberg P, Sharpe MD, Ronco JJ, Renner EL, et al. Liver transplantation in the critically ill: a multicenter Canadian retrospective cohort study. Crit Care 2013;17:R28. 5. Brown RS Jr, Kumar KS, Russo MW, Kinkhabwala M, Rudow DL, Harren P, et al. Model for end-stage liver disease and Child-Turcotte-Pugh score as predictors of pretransplantation disease severity, posttransplantation outcome, and resource utilization in United Network for Organ Sharing status 2A patients. Liver Transpl 2002;8:278-284. 6. Levesque E, Hoti E, Azoulay D, Icha€ı P, Habouchi H, Castaing D, et al. Prospective evaluation of the prognostic scores for cirrhotic patients admitted to an intensive care unit. J Hepatol 2012;56:95-102. 7. Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, et al.; for CANONIC Study Investigators of the EASL– CLIF Consortium. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 2013;144: 1426-1437. 8. Levesque E, Saliba F, Icha€ı P, Samuel D. Outcome of patients with cirrhosis requiring mechanical ventilation in ICU. J Hepatol 2014;60:570-578.
