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Influence of Selected Factors on Survival After Liver Retransplantation
Influence of Selected Factors on Survival After Liver Retransplantation P. Remiszewski, P. Kalinowski, K. Dudek, M. Grodzicki, R. Paluszkiewicz, K. Zieniewicz, and M. Krawczyk ABSTRACT Objective. The aim of this study was to examine the survival of adult liver retransplant recipients depending on selected factors: time from the primary transplantation, cold ischemia time, indications for retransplantation, patient age and United Network for Organ Sharing (UNOS) status. Patients and Methods. Between December 1989 and March 2011, we performed 43 orthotopic liver retransplantations (re-OLTs) among patients aged 20 – 62 years including 24 women and 19 men. The cold ischemia time was 250 – 820 minutes. UNOS status before re-OLT: UNOS 1 (n ⫽ 19; 44%) UNOS 2A (n ⫽ 15; 35%), and UNOS 2B (n ⫽ 4; 9%). The time from OLT to re-OLT was 1–2, 146 days. The indications for re-OLT were arterial thrombosis (n ⫽ 14; 33%), anastomotic biliary complication (n ⫽ 3; 7%), recurrence of the original disease (n ⫽ 9; 21%), hepatic vein thrombosis (n ⫽ 1; 2%), primary nonfunction (PNF) dysfunction (n ⫽ 2; [5%] /6 [14%]), de novo hepatitis C cirrhosis (n ⫽ 2; 5%) and other etiologies (n ⫽ 6; 14%). Results. The 6-year survival among the primary OLT group was 80% compared with 58% among the re-OLT group (P ⫽ .0001). One-year survivals in the re-OLT group according to UNOS status 1, 2A, and 2B were 47%, 60%, and 75%, respectively (P ⫽ .475). There was a low negative correlation between survival time and time between OLT and re-OLT. There was a low positive correlation between survival time and cold ischemia time. There was a low negative correlation between survival time and patient age. Conclusions. There was a significant difference in survival between OLT and re-OLT. There was a correlation between survival time and time to re-OLTx; a shorter time corresponded to longer survival. There was a poor correlation between survival time and patient age. UNOS status before re-OLT and indication for re-OLTx influenced survival. iver retransplantation (re-OLT) is sometimes the only therapeutic option for patients who experience a failure of the hepatic graft.1,2 Liver retransplantation can occur at any time after the primary transplantation.3 The purpose of this study was to examine the outcomes of adult re-OLT recipients depending on time from the first transplantation, cold ischemia time (CIT), indications for retransplantation, patient age, and United Network for Organ Sharing (UNOS) status.
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PATIENTS AND METHODS From December 1989 until the end of March 2011, we performed 911 orthotopic liver transplantations (OLTs), including 45 retransplantations and 2 reretransplantations (5.2%), the latter being
excluded from the analysis. We analyzed the records of 43 re-OLT patients. The patients’ age range was 20 – 62 years (mean 43, SD 11) and there were 24 women and 19 men. Cold ischemia time was 250 – 820 minutes (mean 534 ⫾ 156) UNOS status of the patients before re-OLT was UNOS 1 (n ⫽ 19), UNOS 2A (n ⫽ 15), or UNOS 2B (n ⫽ 4). The time from OLT to re-OLT was 1–2, 146 days (mean⫽444 ⫾ 649).
From the Department of General Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland. Address reprint requests to Piotr Remiszewski, Department of General Transplant and Liver Surgery, Medical University of Warsaw, ul. Banacha 1a, 02-097 Warsaw, Poland. E-mail: [email protected]
© 2011 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/–see front matter doi:10.1016/j.transproceed.2011.08.026
Transplantation Proceedings, 43, 3025–3028 (2011)
3025
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Fig 1. Comparison of survivals in the OLT and re-OLT groups. Indications for re-OLT were hepatic artery thrombosis (HAT; n ⫽ 14), anastomotic biliary complications (n ⫽ 3), recurrence of original disease (n ⫽ 9), hepatic vein thrombosis (n ⫽ 1), primary non function (PNF)/dysfunction (n ⫽ 2/6), de novo hepatitis C cirrhosis (n ⫽ 2) and other etiologies (n ⫽ 6.)
Statistical Analysis Survivals among transplanted versus retransplanted patients are presented as Kaplan-Meier curves that were compared using a log-rank test. Survival among retransplanted patients was evaluated depending on the indication for re-OLT or on UNOS status before re-OLT using the Kaplan-Meier method for comparisons by chisquare test. We evaluated the correlations between survival and time between OLT and re-OLT, cold ischemia time and patient age. We used Statistica (data analysis software system), StatSoft, Inc. (2008), version 8.0. www.statsoft.com.
RESULTS
The two-year survival among the OLT group was 84% compared with 66% among the re-OLT group, with corresponding 6-year-survivals of 80% and 58%, respectively (P ⫽ .0001; log-rank test; Fig 1). The overall survival in the re-OLT group was 0 –14 years (mean 3.31 ⫾ 4.13): alive, 24 (56%); died, 19 (44%). The 1-year survival after re-OLT depending on UNOS status just before re-OLT was UNOS 1, 47%; UNOS 2A, 60%; and UNOS 2B, 75% (P ⫽ .475; chi-square test Fig 2). Survival depended on the indication for re-OLT was highest among patients with anastomotic biliary complications and arterial thrombosis and lowest for those with de novo hepatitis C cirrhosis and PNF/dysfunction (P ⫽ .988; chi-square test; Fig 3).
Fig 2. Kaplan-Meier survivals after re-OLT depending on UNOS status.
FACTORS OF SURVIVAL AFTER RETRANSPLANTATION
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Fig 3. Kaplan-Meier survivals depending on indication for re-OLT.
The correlation between survival and time to re-OLT showed a low negative value (r ⫽ ⫺0.2; r2 ⫽ 0.04; P ⫽ .197). There was a low positive correlation between survival time and cold ischemia time (r ⫽ 0.244; r2 ⫽ 0.059; P ⫽ .229.) There was a low negative correlation between survival time and patient age (r ⫽ ⫺0.13; r2 ⫽ 0.017; P ⫽ .412.). DISCUSSION
The incidence of retransplantation among 911 primary orthotopic liver grafts was 5.2%; it was among the lowest reported worldwide. The typical rate of liver retransplantation ranges between 10% and 20% of primary transplantations,4,5 but some centers report results similar to ours.6 There was a significant 22% difference in survival between primary OLT and re-OLT in favor of the primary procedure. This result was similar to those reported in other analyses such as data from the European Liver Transplant Registry.7 The correlation between liver recipient survival and UNOS status preceding re-OLT is a logical consequence of the severity of the patient’s clinical status. Patients classified as UNOS 2A or 2B category showed better survival than those classified as UNOS 1.8 The survival varied depending on the indication for re-OLT; there was a longer survival among subjects with HAT or biliary anastomotic complications as the indication for re-OLT. The worst survival was observed among patients with PNF or de novo hepatitis C cirrhosis. The difference was not significant, probably owing to the small number of patients.2,9 –11 There was a negative correlation between survival time and interval between the primary OLT and re-OLT; the shorter the time, the longer the survival. This observation confirms the longer survival among patients with HAT as the indication for retransplantation, as shown previously. These procedures were usually early re-OLT.12
Recipient age has been reported in many publications to be a risk factor for poor survival after re-OLT.13,14 Our study supported this observation, because survival time was inversely related to recipient age. In conclusion there was a significant difference in survival time between primary OLT and re-OLT. The 22% difference was not affected by follow-up time. Survival after re-OLT was influenced by the time between primary OLT and re-OLT, UNOS status, patient age, and indication for re-OLT.
REFERENCES 1. Kumar N, Wall WJ, Grant DR, et al: Liver retransplantation. Transplant Proc 31:541, 1999 2. de Carlis L, Slim AO, Giacomoni A, et al: Liver retransplantation: indications and results over a 15-year experience. Transplant Proc 33:1411, 2001 3. Reed A, Howard RJ, Fujita S, et al: Liver retransplantation: a single-center outcome and financial analysis. Transplant Proc 37:1161, 2005 4. Adam R, McMaster P, O’Grady JG, et al: Evolution of liver transplantation in Europe: report of the European Liver Transplant Registry. Liver Transpl 12:1231, 2003 5. Markmann JF, Markowitz JS, Jersiz H, et al: Long-term survival after retransplantation of the liver. Ann Surg 226:408, 1997 6. Perez-Saborido B, Meneu-Diaz JC, Jimenez de los Galanes S, et al: Short- and long-term overall results of liver retransplantation: “Doce de Octubre” Hospital experience. Transplant Proc 41:2441, 2009 7. European Liver Transplant Registry: Available at: http:// www.eltr.org 8. Martin AP, Bartels M, Hauss J, et al: Overview of the MELD score and the UNOS adult liver allocation system. Transplant Proc 39:3169, 2007 9. Pfitzmann R, Benscheidt B, Langrehr JM, et al: Trends and experiences in liver retransplantation over 15 years. Liver Transpl 13:248, 2007 10. Yoo HY, Maheshwari A, Thuluvath PJ: Retransplantation of liver: primary graft nonfunction and hepatitis C virus are associated with worse outcome. Liver Transpl 9:897, 2003
3028 11. Watt KDS, Lyden ER, McCashland TM: Poor survival after liver retransplantation: is hepatitis C to blame? Liver Transpl 9:1019, 2003 12. Sanchez-Bueno F, Acosta F, Ramirez P, et al: Incidence and survival rate of hepatic retransplantation in a series of 300 orthotopic liver transplants. Transplant Proc 32:2671, 2000
REMISZEWSKI, KALINOWSKI, DUDEK ET AL 13. Rosen HR, Prieto M, et al: Validation and refinement of survival models for liver retransplantation. Hepatology 38:460, 2003 14. Bilbao I, Figueras J, Grande L, Clèries M, et al: Risk factors for death following liver retransplantation, Transplant Proc 35:1871, 2003
L
PATIENTS AND METHODS From December 1989 until the end of March 2011, we performed 911 orthotopic liver transplantations (OLTs), including 45 retransplantations and 2 reretransplantations (5.2%), the latter being
excluded from the analysis. We analyzed the records of 43 re-OLT patients. The patients’ age range was 20 – 62 years (mean 43, SD 11) and there were 24 women and 19 men. Cold ischemia time was 250 – 820 minutes (mean 534 ⫾ 156) UNOS status of the patients before re-OLT was UNOS 1 (n ⫽ 19), UNOS 2A (n ⫽ 15), or UNOS 2B (n ⫽ 4). The time from OLT to re-OLT was 1–2, 146 days (mean⫽444 ⫾ 649).
From the Department of General Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland. Address reprint requests to Piotr Remiszewski, Department of General Transplant and Liver Surgery, Medical University of Warsaw, ul. Banacha 1a, 02-097 Warsaw, Poland. E-mail: [email protected]
© 2011 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/–see front matter doi:10.1016/j.transproceed.2011.08.026
Transplantation Proceedings, 43, 3025–3028 (2011)
3025
3026
REMISZEWSKI, KALINOWSKI, DUDEK ET AL
Fig 1. Comparison of survivals in the OLT and re-OLT groups. Indications for re-OLT were hepatic artery thrombosis (HAT; n ⫽ 14), anastomotic biliary complications (n ⫽ 3), recurrence of original disease (n ⫽ 9), hepatic vein thrombosis (n ⫽ 1), primary non function (PNF)/dysfunction (n ⫽ 2/6), de novo hepatitis C cirrhosis (n ⫽ 2) and other etiologies (n ⫽ 6.)
Statistical Analysis Survivals among transplanted versus retransplanted patients are presented as Kaplan-Meier curves that were compared using a log-rank test. Survival among retransplanted patients was evaluated depending on the indication for re-OLT or on UNOS status before re-OLT using the Kaplan-Meier method for comparisons by chisquare test. We evaluated the correlations between survival and time between OLT and re-OLT, cold ischemia time and patient age. We used Statistica (data analysis software system), StatSoft, Inc. (2008), version 8.0. www.statsoft.com.
RESULTS
The two-year survival among the OLT group was 84% compared with 66% among the re-OLT group, with corresponding 6-year-survivals of 80% and 58%, respectively (P ⫽ .0001; log-rank test; Fig 1). The overall survival in the re-OLT group was 0 –14 years (mean 3.31 ⫾ 4.13): alive, 24 (56%); died, 19 (44%). The 1-year survival after re-OLT depending on UNOS status just before re-OLT was UNOS 1, 47%; UNOS 2A, 60%; and UNOS 2B, 75% (P ⫽ .475; chi-square test Fig 2). Survival depended on the indication for re-OLT was highest among patients with anastomotic biliary complications and arterial thrombosis and lowest for those with de novo hepatitis C cirrhosis and PNF/dysfunction (P ⫽ .988; chi-square test; Fig 3).
Fig 2. Kaplan-Meier survivals after re-OLT depending on UNOS status.
FACTORS OF SURVIVAL AFTER RETRANSPLANTATION
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Fig 3. Kaplan-Meier survivals depending on indication for re-OLT.
The correlation between survival and time to re-OLT showed a low negative value (r ⫽ ⫺0.2; r2 ⫽ 0.04; P ⫽ .197). There was a low positive correlation between survival time and cold ischemia time (r ⫽ 0.244; r2 ⫽ 0.059; P ⫽ .229.) There was a low negative correlation between survival time and patient age (r ⫽ ⫺0.13; r2 ⫽ 0.017; P ⫽ .412.). DISCUSSION
The incidence of retransplantation among 911 primary orthotopic liver grafts was 5.2%; it was among the lowest reported worldwide. The typical rate of liver retransplantation ranges between 10% and 20% of primary transplantations,4,5 but some centers report results similar to ours.6 There was a significant 22% difference in survival between primary OLT and re-OLT in favor of the primary procedure. This result was similar to those reported in other analyses such as data from the European Liver Transplant Registry.7 The correlation between liver recipient survival and UNOS status preceding re-OLT is a logical consequence of the severity of the patient’s clinical status. Patients classified as UNOS 2A or 2B category showed better survival than those classified as UNOS 1.8 The survival varied depending on the indication for re-OLT; there was a longer survival among subjects with HAT or biliary anastomotic complications as the indication for re-OLT. The worst survival was observed among patients with PNF or de novo hepatitis C cirrhosis. The difference was not significant, probably owing to the small number of patients.2,9 –11 There was a negative correlation between survival time and interval between the primary OLT and re-OLT; the shorter the time, the longer the survival. This observation confirms the longer survival among patients with HAT as the indication for retransplantation, as shown previously. These procedures were usually early re-OLT.12
Recipient age has been reported in many publications to be a risk factor for poor survival after re-OLT.13,14 Our study supported this observation, because survival time was inversely related to recipient age. In conclusion there was a significant difference in survival time between primary OLT and re-OLT. The 22% difference was not affected by follow-up time. Survival after re-OLT was influenced by the time between primary OLT and re-OLT, UNOS status, patient age, and indication for re-OLT.
REFERENCES 1. Kumar N, Wall WJ, Grant DR, et al: Liver retransplantation. Transplant Proc 31:541, 1999 2. de Carlis L, Slim AO, Giacomoni A, et al: Liver retransplantation: indications and results over a 15-year experience. Transplant Proc 33:1411, 2001 3. Reed A, Howard RJ, Fujita S, et al: Liver retransplantation: a single-center outcome and financial analysis. Transplant Proc 37:1161, 2005 4. Adam R, McMaster P, O’Grady JG, et al: Evolution of liver transplantation in Europe: report of the European Liver Transplant Registry. Liver Transpl 12:1231, 2003 5. Markmann JF, Markowitz JS, Jersiz H, et al: Long-term survival after retransplantation of the liver. Ann Surg 226:408, 1997 6. Perez-Saborido B, Meneu-Diaz JC, Jimenez de los Galanes S, et al: Short- and long-term overall results of liver retransplantation: “Doce de Octubre” Hospital experience. Transplant Proc 41:2441, 2009 7. European Liver Transplant Registry: Available at: http:// www.eltr.org 8. Martin AP, Bartels M, Hauss J, et al: Overview of the MELD score and the UNOS adult liver allocation system. Transplant Proc 39:3169, 2007 9. Pfitzmann R, Benscheidt B, Langrehr JM, et al: Trends and experiences in liver retransplantation over 15 years. Liver Transpl 13:248, 2007 10. Yoo HY, Maheshwari A, Thuluvath PJ: Retransplantation of liver: primary graft nonfunction and hepatitis C virus are associated with worse outcome. Liver Transpl 9:897, 2003
3028 11. Watt KDS, Lyden ER, McCashland TM: Poor survival after liver retransplantation: is hepatitis C to blame? Liver Transpl 9:1019, 2003 12. Sanchez-Bueno F, Acosta F, Ramirez P, et al: Incidence and survival rate of hepatic retransplantation in a series of 300 orthotopic liver transplants. Transplant Proc 32:2671, 2000
REMISZEWSKI, KALINOWSKI, DUDEK ET AL 13. Rosen HR, Prieto M, et al: Validation and refinement of survival models for liver retransplantation. Hepatology 38:460, 2003 14. Bilbao I, Figueras J, Grande L, Clèries M, et al: Risk factors for death following liver retransplantation, Transplant Proc 35:1871, 2003