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Liver Retransplantation: The Changing Scenario in a Tertiary Medical Center
Liver Retransplantation: The Changing Scenario in a Tertiary Medical Center I. Palomo López*, A. Molina Raya, M. Domínguez Bastante, T. Villegas Herrera, M.A. Herrero Torres, N. Zambudio Carroll, and J.M. Villar del Moral General Surgery Unit, University Hospital Virgen de las Nieves, Granada, Spain
ABSTRACT Aim. To analyze the causes of liver retransplantation (LRT), which mostly depend on recipient factors. Materials and Methods. A descriptive, observational, and unicentric study including patients who underwent an LRT in a tertiary medical center between April 2002 and December 2018. Recipient, donor, and liver transplant data were collected. Results. During the period under review a total of 468 transplants were made; among them, 32 (6.8%) were LRT. The most common indication (25%) was hepatic artery thrombosis (HAT) developing ischemic cholangiopathy followed by chronic rejection (21.8%). Late LRT was performed in 71.8%. A total of 96.8% of donations were after brain death with a donor median age of 65 years. Six patients (18.7%) had HAT as a postoperative complication. The recipients’ 3-, 6-, and 12-month overall survival was 72.7%, 54.6%, and 51.5%, respectively, and the 5-year was 46.8%. Leading cause of death was septic shock (42.1%). Conclusion. In our patients, the most common cause of LRT is HAT. We had an LRT rate of 6.8%, which is consistent with national and international registers.
A
LTHOUGH significant advances of liver transplantation (LT) had been achieved in the last few decades, numerous early and late complications could lead to graft failure and its sole therapeutic option: liver retransplantation (LRT) [1]. In Spain, rates reach numbers between 7% and 13%, establishing a relevant number of LRT rates 1 under 10% in the 6th Consensus Meeting of the Spanish Liver Transplantation Society. This value could turn into a quality indicator at immediate post-transplant [2]. Different series reveal that hepatic artery thrombosis (HAT) is the most common indication, followed by chronic rejection (CR). In respect to recipient overall survival, national reports provide annual rates around 67% [2]. MATERIALS AND METHODS We performed a single-center observational, retrospective study including patients who underwent LRT in a tertiary medical center between January 2002 and December 2018. LRTs were classified as early (within the first 6 months after primary transplant) or late (after 6 months). In terms of data analysis, qualitative variables are expressed as frequencies and absolute numbers, and quantitative ª 2020 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, XX, 1e3 (2020)
variables as median and interquartile range. We collected recipient variables such as age, sex, body mass index, Child-Pugh, MELD, and time and indication of the LRT. Perioperative data were attained, such as surgical times, ischemia times (total, cold, and warm), and postoperative complications (arterial, biliary, portal, and early graft failure [EGF]). MEAF score and Olthoff criteria were calculated to predict EGF. MEAF score uses total bilirubin (TB) on the third postoperative day, international normalized ratio and aspartate transaminase within the first 3 postoperative days [3]. Olthoff criteria named EGF when transaminases are >2000 IU within the first 7 days postoperatively and TB >10 mg/dL and international normalized ratio >1.6 at the seventh postoperative day [4]. Donor variables were analyzed including age and type of donor (brain death, cardiac death donors type II and type III). Recipients’ overall survival was calculated at 3, 6, and 12 months. IBM SPSS Statistics 21 was used for data analysis.
*Address correspondence to Irina Palomo López, General Surgery Unit of University Hospital Virgen de las Nieves, Avda. de las Fuerzas Armadas, 2, 18014, Granada, Spain. Tel: 695 905 415. E-mail: [email protected] 0041-1345/20 https://doi.org/10.1016/j.transproceed.2019.12.026
1
2
LÓPEZ, RAYA, BASTANTE ET AL Table 1. Demographics and Characteristics of Patients
Variables
Male sex Age BMI (kg/m2) Child-Pugh classification score A B C MELD score Timing of LRT Early Late
(N ¼ 32) Qualitative Variables (N ¼ 32) Quantitative (Frequencies and Variables Absolute Numbers) (Median and IR)
32 (93.7%) 54 (38-70) 27.7 (22.4-32.9)
12 (37.5%) 19 (59%) 1 (3.5%) 17.5 (5.75-29.25) 9 (28.2%) 33 (71.8%)
Abbreviations: BMI, body mass index; IR, interquartile range; LRT, liver retransplantation.
RESULTS
During the period under review a total of 468 transplants were made. Thirty-two of them (6.8%) underwent an LRT. Demographics and characteristics of patients are described in Table 1. The indications of LRT were: 8 HAT with ischemic cholangiopathy (IC) (25%), 7 CR (21.8%), 6 nonarterial IC (18.7%), 4 EGF (12.5%), 1 (3.1%) HCV reinfection, 1 (3.1%) portal thrombosis, and 5 nonregistered causes. The 35.2% of patients met Olthoff criteria and the median MEAF score was 4.46 (2.35-6.57). Vascular and biliary retransplant complications were the following: 10 (31.2%) HATd6 of them (60%) were a near HAT (during the first postoperative month), and 4 of them (40%) were a late HAT (1 month later)d4 (12.5%) hepatic arterial stenosis, 2 (6.24%) portal thrombosis, and 9 (28.1%) biliary complications. The median of surgical time was 460 minutes (267-653), total ischemia time was 310 minutes (182-438): 265 (127-403) of cold ischemia and 42.5 (18.5-67.5) of warm ischemia. A total of 96.8% of donations were after brain death with a donor median age of 65 years (43-87). Overall survival at 3, 6, and 12 months was 72.7%, 54.6%, and 51.5%, respectively. The leading cause of death was septic shock (42.1%) followed by EGF (15.7%), neoplastic disease after LRT (15.7%), perioperative factors (5.2%), and causes outside the LRT (21%).
in graft failure leading inexorably to the LRT could depend on the recipient or donor. Regarding the recipient, there are comorbidities such as higher body mass index, MELD, and Child-Pugh scores that could increase significantly the probability of EGF, which may determine the need of LRT, as Pareja et al analyzed [3]. In relation to donors, the expansion of the donor pool in the last year has led to the use of grafts because of more donors with higher risk indexes than previous decades, as Sanjeev et al pointed out [5]. It can explain the EGF and nonfunction occasionally found, which sole therapeutic solution is LRT. Our finding of 6.8% of the whole series being LRT is inside the standards of the quality criteria set at the last national consensus [2]. The main cause of LRT was HAT with IC, as claimed by most authors such as Mourad et al [6] or Marudanayagam et al [7]. HAT was noticed as the main surgical complication after LT. For the development of this devastating problem, LRT itself can be an important risk factor. Indeed, it is associated with a six-fold greater risk regarding primary transplantation, as a systematic review concluded [8]. The relevance of the high incidence and prevalence of HAT in our series has made us consider new preventive approaches. First, we propose some of them such as systematic intraoperative hepatic artery flow measurement in primary LT and LRT, as Abbasoglu et al also showed [9]. On the other hand, it is important to keep in mind the option of performance of nonanatomical arterial reconstructions in cases of poor-quality recipient hepatic artery, as Li et al also mentioned [10]. Finally, we probably should have a lower threshold for the use of postoperative antiaggregation in complex cases. Regarding the limitations of the study, we consider the long time frame of the transplants included, with a learning curve in the first years, along with the scarce number of patients derived from an unicentric analysis, that can impose some bias to our conclusions. However, the strict follow-up of the patients, with no losses, can be considered a strength of the present study. CONCLUSION
A low to medium volume LT unit can obtain LRT rates aligned with current standards. In our experience, the most common cause of LRT was HAT causing IC, followed by CR. Because of that, a narrow and long-term follow-up and an early detection and treatment of these complications are mandatory.
DISCUSSION
In this review of the practice of a low to medium volume LT unit, we have obtained an LRT rate of 6.8%, of which the most common indication was HAT with IC. The most frequent and severe postoperative morbidity made reference to vascular complications, mostly with the development of HAT. In recent years, LT rate has showed a global rise, due to the increase of available grafts and some new indications under scrutiny. Because of that, LRT indications have became an issue of debate among experts. Factors involved
REFERENCES [1] Biggins SW. Futility and rationing in liver retransplantation: when and how can we say no? J Hepatol 2012;56:1404e11. [2] Pardo F, Pons JA, Castells L, Colmenero J, Gómez MA, Lladó L, et al. VI Consensus document by the Spanish Liver Transplantation Society. Cir Esp 2018;96:326e41. [3] Pareja E, Cortes M, Hervas D, Mir J, Valdivieso A, Castell JV, et al. A score model for the continuous grading for early allograft dysfunction severity. Liver Transpl 2015;21:38e46. [4] Olthoff KM, Kulik L, Samstein B, Kaminsky M, Abecassis M, Emond J, et al. Validation of a current definition of early allograft
LIVER RETRANSPLANTATION: THE CHANGING SCENARIO dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl 2010;16:943e9. [5] Sanjeev KA, Sumeet KA, Yi P, Peter S, Ray K, Ajay KI. Development of organ-specific donor risk indices. Liver Transpl 2012;18:395e404. [6] Mourad MM, Liossis C, Gunson BK, Mergental H, Isaac J, Muiesan P, et al. Etiology and management of hepatic artery thrombosis after adult liver transplantation. Liver Transpl 2014;20: 713e23. [7] Marudanayagam R, Shanmugam V, Sandhu B, Gunson BK, Mirza DF, Mayer D, et al. Liver retransplantation in adults: a single-centre, 25-year experience. HPB (Oxford) 2010;3:217e24.
3 [8] Bekker J, Ploem S, De Jong KP. Early hepatic artery thrombosis after liver transplantation: a systematic review of the incidence, outcome and risk factors. Am J Transplant 2009;9:746e57. [9] Abbasoglu O, Levy MF, Testa G, Obiekwe S, Brkic BS, Jennings LW, et al. Does intraoperative hepatic artery flow predict arterial complications after liver transplantation? Transplantation 1998;5:598e601. [10] Li PC, Thorat A, Jeng LB, Yang HR, Li ML, Yeh CC, et al. Hepatic artery reconstruction in living donor liver transplantation using surgical loupes: achieving low rate of hepatic arterial thrombosis in 741 consecutive recipients-tips and tricks to overcome the poor hepatic arterial flow. Liver Transpl 2017;7:887e98.
ABSTRACT Aim. To analyze the causes of liver retransplantation (LRT), which mostly depend on recipient factors. Materials and Methods. A descriptive, observational, and unicentric study including patients who underwent an LRT in a tertiary medical center between April 2002 and December 2018. Recipient, donor, and liver transplant data were collected. Results. During the period under review a total of 468 transplants were made; among them, 32 (6.8%) were LRT. The most common indication (25%) was hepatic artery thrombosis (HAT) developing ischemic cholangiopathy followed by chronic rejection (21.8%). Late LRT was performed in 71.8%. A total of 96.8% of donations were after brain death with a donor median age of 65 years. Six patients (18.7%) had HAT as a postoperative complication. The recipients’ 3-, 6-, and 12-month overall survival was 72.7%, 54.6%, and 51.5%, respectively, and the 5-year was 46.8%. Leading cause of death was septic shock (42.1%). Conclusion. In our patients, the most common cause of LRT is HAT. We had an LRT rate of 6.8%, which is consistent with national and international registers.
A
LTHOUGH significant advances of liver transplantation (LT) had been achieved in the last few decades, numerous early and late complications could lead to graft failure and its sole therapeutic option: liver retransplantation (LRT) [1]. In Spain, rates reach numbers between 7% and 13%, establishing a relevant number of LRT rates 1 under 10% in the 6th Consensus Meeting of the Spanish Liver Transplantation Society. This value could turn into a quality indicator at immediate post-transplant [2]. Different series reveal that hepatic artery thrombosis (HAT) is the most common indication, followed by chronic rejection (CR). In respect to recipient overall survival, national reports provide annual rates around 67% [2]. MATERIALS AND METHODS We performed a single-center observational, retrospective study including patients who underwent LRT in a tertiary medical center between January 2002 and December 2018. LRTs were classified as early (within the first 6 months after primary transplant) or late (after 6 months). In terms of data analysis, qualitative variables are expressed as frequencies and absolute numbers, and quantitative ª 2020 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, XX, 1e3 (2020)
variables as median and interquartile range. We collected recipient variables such as age, sex, body mass index, Child-Pugh, MELD, and time and indication of the LRT. Perioperative data were attained, such as surgical times, ischemia times (total, cold, and warm), and postoperative complications (arterial, biliary, portal, and early graft failure [EGF]). MEAF score and Olthoff criteria were calculated to predict EGF. MEAF score uses total bilirubin (TB) on the third postoperative day, international normalized ratio and aspartate transaminase within the first 3 postoperative days [3]. Olthoff criteria named EGF when transaminases are >2000 IU within the first 7 days postoperatively and TB >10 mg/dL and international normalized ratio >1.6 at the seventh postoperative day [4]. Donor variables were analyzed including age and type of donor (brain death, cardiac death donors type II and type III). Recipients’ overall survival was calculated at 3, 6, and 12 months. IBM SPSS Statistics 21 was used for data analysis.
*Address correspondence to Irina Palomo López, General Surgery Unit of University Hospital Virgen de las Nieves, Avda. de las Fuerzas Armadas, 2, 18014, Granada, Spain. Tel: 695 905 415. E-mail: [email protected] 0041-1345/20 https://doi.org/10.1016/j.transproceed.2019.12.026
1
2
LÓPEZ, RAYA, BASTANTE ET AL Table 1. Demographics and Characteristics of Patients
Variables
Male sex Age BMI (kg/m2) Child-Pugh classification score A B C MELD score Timing of LRT Early Late
(N ¼ 32) Qualitative Variables (N ¼ 32) Quantitative (Frequencies and Variables Absolute Numbers) (Median and IR)
32 (93.7%) 54 (38-70) 27.7 (22.4-32.9)
12 (37.5%) 19 (59%) 1 (3.5%) 17.5 (5.75-29.25) 9 (28.2%) 33 (71.8%)
Abbreviations: BMI, body mass index; IR, interquartile range; LRT, liver retransplantation.
RESULTS
During the period under review a total of 468 transplants were made. Thirty-two of them (6.8%) underwent an LRT. Demographics and characteristics of patients are described in Table 1. The indications of LRT were: 8 HAT with ischemic cholangiopathy (IC) (25%), 7 CR (21.8%), 6 nonarterial IC (18.7%), 4 EGF (12.5%), 1 (3.1%) HCV reinfection, 1 (3.1%) portal thrombosis, and 5 nonregistered causes. The 35.2% of patients met Olthoff criteria and the median MEAF score was 4.46 (2.35-6.57). Vascular and biliary retransplant complications were the following: 10 (31.2%) HATd6 of them (60%) were a near HAT (during the first postoperative month), and 4 of them (40%) were a late HAT (1 month later)d4 (12.5%) hepatic arterial stenosis, 2 (6.24%) portal thrombosis, and 9 (28.1%) biliary complications. The median of surgical time was 460 minutes (267-653), total ischemia time was 310 minutes (182-438): 265 (127-403) of cold ischemia and 42.5 (18.5-67.5) of warm ischemia. A total of 96.8% of donations were after brain death with a donor median age of 65 years (43-87). Overall survival at 3, 6, and 12 months was 72.7%, 54.6%, and 51.5%, respectively. The leading cause of death was septic shock (42.1%) followed by EGF (15.7%), neoplastic disease after LRT (15.7%), perioperative factors (5.2%), and causes outside the LRT (21%).
in graft failure leading inexorably to the LRT could depend on the recipient or donor. Regarding the recipient, there are comorbidities such as higher body mass index, MELD, and Child-Pugh scores that could increase significantly the probability of EGF, which may determine the need of LRT, as Pareja et al analyzed [3]. In relation to donors, the expansion of the donor pool in the last year has led to the use of grafts because of more donors with higher risk indexes than previous decades, as Sanjeev et al pointed out [5]. It can explain the EGF and nonfunction occasionally found, which sole therapeutic solution is LRT. Our finding of 6.8% of the whole series being LRT is inside the standards of the quality criteria set at the last national consensus [2]. The main cause of LRT was HAT with IC, as claimed by most authors such as Mourad et al [6] or Marudanayagam et al [7]. HAT was noticed as the main surgical complication after LT. For the development of this devastating problem, LRT itself can be an important risk factor. Indeed, it is associated with a six-fold greater risk regarding primary transplantation, as a systematic review concluded [8]. The relevance of the high incidence and prevalence of HAT in our series has made us consider new preventive approaches. First, we propose some of them such as systematic intraoperative hepatic artery flow measurement in primary LT and LRT, as Abbasoglu et al also showed [9]. On the other hand, it is important to keep in mind the option of performance of nonanatomical arterial reconstructions in cases of poor-quality recipient hepatic artery, as Li et al also mentioned [10]. Finally, we probably should have a lower threshold for the use of postoperative antiaggregation in complex cases. Regarding the limitations of the study, we consider the long time frame of the transplants included, with a learning curve in the first years, along with the scarce number of patients derived from an unicentric analysis, that can impose some bias to our conclusions. However, the strict follow-up of the patients, with no losses, can be considered a strength of the present study. CONCLUSION
A low to medium volume LT unit can obtain LRT rates aligned with current standards. In our experience, the most common cause of LRT was HAT causing IC, followed by CR. Because of that, a narrow and long-term follow-up and an early detection and treatment of these complications are mandatory.
DISCUSSION
In this review of the practice of a low to medium volume LT unit, we have obtained an LRT rate of 6.8%, of which the most common indication was HAT with IC. The most frequent and severe postoperative morbidity made reference to vascular complications, mostly with the development of HAT. In recent years, LT rate has showed a global rise, due to the increase of available grafts and some new indications under scrutiny. Because of that, LRT indications have became an issue of debate among experts. Factors involved
REFERENCES [1] Biggins SW. Futility and rationing in liver retransplantation: when and how can we say no? J Hepatol 2012;56:1404e11. [2] Pardo F, Pons JA, Castells L, Colmenero J, Gómez MA, Lladó L, et al. VI Consensus document by the Spanish Liver Transplantation Society. Cir Esp 2018;96:326e41. [3] Pareja E, Cortes M, Hervas D, Mir J, Valdivieso A, Castell JV, et al. A score model for the continuous grading for early allograft dysfunction severity. Liver Transpl 2015;21:38e46. [4] Olthoff KM, Kulik L, Samstein B, Kaminsky M, Abecassis M, Emond J, et al. Validation of a current definition of early allograft
LIVER RETRANSPLANTATION: THE CHANGING SCENARIO dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl 2010;16:943e9. [5] Sanjeev KA, Sumeet KA, Yi P, Peter S, Ray K, Ajay KI. Development of organ-specific donor risk indices. Liver Transpl 2012;18:395e404. [6] Mourad MM, Liossis C, Gunson BK, Mergental H, Isaac J, Muiesan P, et al. Etiology and management of hepatic artery thrombosis after adult liver transplantation. Liver Transpl 2014;20: 713e23. [7] Marudanayagam R, Shanmugam V, Sandhu B, Gunson BK, Mirza DF, Mayer D, et al. Liver retransplantation in adults: a single-centre, 25-year experience. HPB (Oxford) 2010;3:217e24.
3 [8] Bekker J, Ploem S, De Jong KP. Early hepatic artery thrombosis after liver transplantation: a systematic review of the incidence, outcome and risk factors. Am J Transplant 2009;9:746e57. [9] Abbasoglu O, Levy MF, Testa G, Obiekwe S, Brkic BS, Jennings LW, et al. Does intraoperative hepatic artery flow predict arterial complications after liver transplantation? Transplantation 1998;5:598e601. [10] Li PC, Thorat A, Jeng LB, Yang HR, Li ML, Yeh CC, et al. Hepatic artery reconstruction in living donor liver transplantation using surgical loupes: achieving low rate of hepatic arterial thrombosis in 741 consecutive recipients-tips and tricks to overcome the poor hepatic arterial flow. Liver Transpl 2017;7:887e98.