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Liver Transplantation Outcomes Using Grafts From Donors Older Than the Age of 80 Years
Liver Transplantation Outcomes Using Grafts From Donors Older Than the Age of 80 Years A.V. Rabelo*, M.J. Alvarez, C.S.M. Méndez, M.T. Villegas, K. MGraneroa, A. Becerra, M. Dominguez, A.M. Raya, M. Exposito, and Y.F. Suárez Hospital Universitario de Granada, Cirugía General y Digestiva, Granada, Spain
ABSTRACT We performed a retrospective cohort study between 2002 and 2014 to compare liver transplantation outcomes between recipients of grafts from donors older than and younger than the age of 80 years. Numerical variables were compared with the Student t test when their distribution was normal and the Mann-Whitney test when it was not, whereas categorical variables were compared with Pearson chi-squared test or Fisher test, as appropriate; P < .05 was considered significant. The study included 312 patients with organs from donors younger than 80 years of age and 17 with organs from older donors. The 2 recipient groups did not significantly differ in weight, height, gender, body mass index (BMI), CHILD or MELD score, intensive care unit (ICU) or hospital stay, need for intraoperative hemoderivatives, postreperfusion syndrome, biliary or vascular complications, ischemic cholangiopathy, number of repeat surgeries, graft rejection, retransplantation, or survival at 6 months. Although earlier studies considered livers from elderly donors to be suboptimal, our results support the proposition that octogenarian donors can be an excellent source of liver grafts.
S
PAIN has always been a leading nation in liver transplantation [1], but the difference between demand and supply is increasingly wide [2,3], leading to longer waiting times and increased mortality among potential recipients [1e3]. In our setting, this problem has been addressed by developing alternatives to conventional liver transplantation, including the use of split-liver grafts and grafts from asystolic and elderly donors [4]. The main objective of the present study was to compare liver transplantation outcomes between recipients of grafts from donors older than and younger than the age of 80 years. MATERIALS AND METHODS A retrospective cohort study was performed of the 329 consecutive liver transplantations performed in our center between 2002 and 2014; 312 of the grafts were from donors younger than 80 years of age and 17 were from older donors. Recipients were followed up for at least 6 months. Numerical variables were compared with the Student t test when their distribution was normal and the MannWhitney test when it was not; categorical variables were compared with Pearson chi-squared test when test conditions were met and Fisher test when they were not; P < .05 was considered significant.
RESULTS
The 17 patients receiving organs from donors older than 80 years (range, 80e85 years) had a mean age of 53 years, mean body mass index (BMI) of 29.5, median CHILD score of 8 and median MELD score of 14 at the time of the transplantation, median intensive care unit (ICU) stay of 4 days, and median hospital stay of 21 days. No statistically significant difference was found between the 17 patients receiving grafts from donors older than 80 years old and the 312 receiving grafts from the younger donors in height, gender, BMI, CHILD or MELD score, ICU or hospital stay, need for intraoperative hemoderivatives, number of readmissions, or time on the waiting list. In both recipient groups, the most frequent etiology of liver failure was alcohol-related disease (76.5% in recipients from donors 80 years vs 40.4% in those from donors <80 years), the most frequent blood group was O (61. 5% vs 41.9%, respectively), and the graft was almost always *Address correspondence to Andrea Vílchez Rabelo, Hospital Universitario de Granada, Cirugía General y Digestiva, Avenida de Las Fuerzas Armadas, S/N, Granada, Spain. E-mail: [email protected]
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.10.004
Transplantation Proceedings, 47, 2645e2646 (2015)
2645
2646
derived from brain-dead donors (100% vs 95.0%, respectively). Bivariate studies also found no statistically significant difference between recipient groups in the following: postreperfusion syndrome (5.88% [n ¼ 1] of recipients from donors 80 years vs 14.2% [n ¼ 45] of recipients from donors <80 years; P ¼ .136); biliary complications (11.76% [n ¼ 2] vs (16.02% [n ¼ 50], respectively; P ¼ .317), with stenosis being the most frequent in both groups; vascular complications (11.76% [n ¼ 2] vs 17.62% [n ¼ 55]; P ¼ .739), with arterial complications being the most frequent type in recipients from donors <80 years (83.64% [n ¼ 46]), primarily arterial stenosis (56.36%). Portal complications were observed in only 9 (16.36%) of this group of recipients, 52 of whom had a history of previous portal thrombosis. Among recipients of grafts from donors older than 80 years, portal thrombosis was only reported in 2, both whom had a history of thrombectomy for previous portal thrombosis, and there was no case of arterial complication. There was also no significant difference between recipient groups in ischemic cholangiopathy (0% in recipients from donors 80 years vs 6.09% [n ¼ 19]); in those from donors <80 years (P ¼ 1); in number of repeat surgeries (17.64% [n ¼3 ] vs 17.30% [n ¼ 54]; P ¼ .16), with hemoperitoneum being the most frequent motive in both groups; in graft rejection (23.52 % [n ¼ 4] vs 21.79% [n ¼ 68]; P ¼ .36), with acute rejection being the most frequent type in both groups; in need for retransplantation (11.76% [n ¼ 2] vs 4.80% [n ¼ 15]); P ¼ .070); or in 6-month survival (70.58% [n ¼ 12] vs 68.91% [n ¼ 215]; P ¼ 1). DISCUSSION
The relationship between donor age and liver transplantation outcomes has been widely studied, with controversial results. Although earlier studies tended to associate higher donor age with increased morbidity-mortality [5], there have been numerous reports of highly promising outcomes using grafts from elderly donors [6e8]. Our data also support this ageindependent approach, evidencing no significant difference between recipients of organs from donors who are older or younger than 80 years of age in biliary, arterial, or portal complications, in the number of repeat surgeries or retransplantations, or in 6-month survival rates. These results suggest that grafts from octogenarian donors can be an excellent source for liver transplantations
RABELO, ALVAREZ, MÉNDEZ ET AL
after application of the appropriate criteria, which are based on the characteristics of the donor in our center. Biopsy findings are also taken into account in some settings. Study weaknesses include its retrospective design and restriction to a single center. Moreover, the number of donors older than the age of 80 years was small, attributable to the strict eligibility criteria, although we applied potent statistical tests. Within these limitations, the results support the policy adopted at our center, which is that age per se should not be considered an exclusion criterion and that numerous other factors must be taken into account. These include the presence/absence of the following: obesity, which influences the degree of hepatic steatosis; prolonged ICU stay; cardiorespiratory arrests; and severe arteriosclerosis, among other diseases. Because arterial complications are the most widely feared outcome, some groups consider that grafts from elderly donors should not be used in retransplantation or in patients with hepatocarcinoma or those who have undergone multiple transarterial chemoembolization procedures. In conclusion, further research is required in larger samples of elderly donors to confirm the promising outcomes obtained at our center using grafts from donors older than the age of 80 years.
REFERENCES [1] Organización Nacional de Trasplantes (ONT) 2014 [Internet]. Spain: ONT, https://www.ont.es/; 1995 [accessed 07.15]. [2] Franco C, Martínez J, Bellido C, et al. Results of liver transplants from donors aged 70 plus: analysis of Andalusian transplant register. Transplant Proc 2013;45:3647e9. [3] Darius T, Monbaliu D, Jochmans I, et al. Septuagenarian and octogenarian donors provide excellent liver grafts for transplantation. Transplant Proc 2012;44:2861e7. [4] Feng S, Goodrich NP, Bargg-gresham JL, et al. Characteristics associated with liver graft failure: the concept of a donor risk index. Am J Trasplant 2006;6:783. [5] Marino IR, Doyle HR, Doria C, et al. Outcome of liver transplantation using donors 60 to 79 years old. Transplant Proc 1995;27:1184. [6] Zhao Y, Lo CM, Liu CL, et al. Use of elderly donors (60 years) for liver transplantation. Asian J Surg 2004;27:114. [7] Oh CK, Sanfey HA, Pelletier SJ, et al. Implication of advanced donor age on the outcome of liver transplantation. Clin Transplant 2000;14:386. [8] Gastaca M, Valdivieso A, Pijoa J. Donors older than 70 years in liver transplantation. Transplant Proc 2005;37:3851.
ABSTRACT We performed a retrospective cohort study between 2002 and 2014 to compare liver transplantation outcomes between recipients of grafts from donors older than and younger than the age of 80 years. Numerical variables were compared with the Student t test when their distribution was normal and the Mann-Whitney test when it was not, whereas categorical variables were compared with Pearson chi-squared test or Fisher test, as appropriate; P < .05 was considered significant. The study included 312 patients with organs from donors younger than 80 years of age and 17 with organs from older donors. The 2 recipient groups did not significantly differ in weight, height, gender, body mass index (BMI), CHILD or MELD score, intensive care unit (ICU) or hospital stay, need for intraoperative hemoderivatives, postreperfusion syndrome, biliary or vascular complications, ischemic cholangiopathy, number of repeat surgeries, graft rejection, retransplantation, or survival at 6 months. Although earlier studies considered livers from elderly donors to be suboptimal, our results support the proposition that octogenarian donors can be an excellent source of liver grafts.
S
PAIN has always been a leading nation in liver transplantation [1], but the difference between demand and supply is increasingly wide [2,3], leading to longer waiting times and increased mortality among potential recipients [1e3]. In our setting, this problem has been addressed by developing alternatives to conventional liver transplantation, including the use of split-liver grafts and grafts from asystolic and elderly donors [4]. The main objective of the present study was to compare liver transplantation outcomes between recipients of grafts from donors older than and younger than the age of 80 years. MATERIALS AND METHODS A retrospective cohort study was performed of the 329 consecutive liver transplantations performed in our center between 2002 and 2014; 312 of the grafts were from donors younger than 80 years of age and 17 were from older donors. Recipients were followed up for at least 6 months. Numerical variables were compared with the Student t test when their distribution was normal and the MannWhitney test when it was not; categorical variables were compared with Pearson chi-squared test when test conditions were met and Fisher test when they were not; P < .05 was considered significant.
RESULTS
The 17 patients receiving organs from donors older than 80 years (range, 80e85 years) had a mean age of 53 years, mean body mass index (BMI) of 29.5, median CHILD score of 8 and median MELD score of 14 at the time of the transplantation, median intensive care unit (ICU) stay of 4 days, and median hospital stay of 21 days. No statistically significant difference was found between the 17 patients receiving grafts from donors older than 80 years old and the 312 receiving grafts from the younger donors in height, gender, BMI, CHILD or MELD score, ICU or hospital stay, need for intraoperative hemoderivatives, number of readmissions, or time on the waiting list. In both recipient groups, the most frequent etiology of liver failure was alcohol-related disease (76.5% in recipients from donors 80 years vs 40.4% in those from donors <80 years), the most frequent blood group was O (61. 5% vs 41.9%, respectively), and the graft was almost always *Address correspondence to Andrea Vílchez Rabelo, Hospital Universitario de Granada, Cirugía General y Digestiva, Avenida de Las Fuerzas Armadas, S/N, Granada, Spain. E-mail: [email protected]
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.10.004
Transplantation Proceedings, 47, 2645e2646 (2015)
2645
2646
derived from brain-dead donors (100% vs 95.0%, respectively). Bivariate studies also found no statistically significant difference between recipient groups in the following: postreperfusion syndrome (5.88% [n ¼ 1] of recipients from donors 80 years vs 14.2% [n ¼ 45] of recipients from donors <80 years; P ¼ .136); biliary complications (11.76% [n ¼ 2] vs (16.02% [n ¼ 50], respectively; P ¼ .317), with stenosis being the most frequent in both groups; vascular complications (11.76% [n ¼ 2] vs 17.62% [n ¼ 55]; P ¼ .739), with arterial complications being the most frequent type in recipients from donors <80 years (83.64% [n ¼ 46]), primarily arterial stenosis (56.36%). Portal complications were observed in only 9 (16.36%) of this group of recipients, 52 of whom had a history of previous portal thrombosis. Among recipients of grafts from donors older than 80 years, portal thrombosis was only reported in 2, both whom had a history of thrombectomy for previous portal thrombosis, and there was no case of arterial complication. There was also no significant difference between recipient groups in ischemic cholangiopathy (0% in recipients from donors 80 years vs 6.09% [n ¼ 19]); in those from donors <80 years (P ¼ 1); in number of repeat surgeries (17.64% [n ¼3 ] vs 17.30% [n ¼ 54]; P ¼ .16), with hemoperitoneum being the most frequent motive in both groups; in graft rejection (23.52 % [n ¼ 4] vs 21.79% [n ¼ 68]; P ¼ .36), with acute rejection being the most frequent type in both groups; in need for retransplantation (11.76% [n ¼ 2] vs 4.80% [n ¼ 15]); P ¼ .070); or in 6-month survival (70.58% [n ¼ 12] vs 68.91% [n ¼ 215]; P ¼ 1). DISCUSSION
The relationship between donor age and liver transplantation outcomes has been widely studied, with controversial results. Although earlier studies tended to associate higher donor age with increased morbidity-mortality [5], there have been numerous reports of highly promising outcomes using grafts from elderly donors [6e8]. Our data also support this ageindependent approach, evidencing no significant difference between recipients of organs from donors who are older or younger than 80 years of age in biliary, arterial, or portal complications, in the number of repeat surgeries or retransplantations, or in 6-month survival rates. These results suggest that grafts from octogenarian donors can be an excellent source for liver transplantations
RABELO, ALVAREZ, MÉNDEZ ET AL
after application of the appropriate criteria, which are based on the characteristics of the donor in our center. Biopsy findings are also taken into account in some settings. Study weaknesses include its retrospective design and restriction to a single center. Moreover, the number of donors older than the age of 80 years was small, attributable to the strict eligibility criteria, although we applied potent statistical tests. Within these limitations, the results support the policy adopted at our center, which is that age per se should not be considered an exclusion criterion and that numerous other factors must be taken into account. These include the presence/absence of the following: obesity, which influences the degree of hepatic steatosis; prolonged ICU stay; cardiorespiratory arrests; and severe arteriosclerosis, among other diseases. Because arterial complications are the most widely feared outcome, some groups consider that grafts from elderly donors should not be used in retransplantation or in patients with hepatocarcinoma or those who have undergone multiple transarterial chemoembolization procedures. In conclusion, further research is required in larger samples of elderly donors to confirm the promising outcomes obtained at our center using grafts from donors older than the age of 80 years.
REFERENCES [1] Organización Nacional de Trasplantes (ONT) 2014 [Internet]. Spain: ONT, https://www.ont.es/; 1995 [accessed 07.15]. [2] Franco C, Martínez J, Bellido C, et al. Results of liver transplants from donors aged 70 plus: analysis of Andalusian transplant register. Transplant Proc 2013;45:3647e9. [3] Darius T, Monbaliu D, Jochmans I, et al. Septuagenarian and octogenarian donors provide excellent liver grafts for transplantation. Transplant Proc 2012;44:2861e7. [4] Feng S, Goodrich NP, Bargg-gresham JL, et al. Characteristics associated with liver graft failure: the concept of a donor risk index. Am J Trasplant 2006;6:783. [5] Marino IR, Doyle HR, Doria C, et al. Outcome of liver transplantation using donors 60 to 79 years old. Transplant Proc 1995;27:1184. [6] Zhao Y, Lo CM, Liu CL, et al. Use of elderly donors (60 years) for liver transplantation. Asian J Surg 2004;27:114. [7] Oh CK, Sanfey HA, Pelletier SJ, et al. Implication of advanced donor age on the outcome of liver transplantation. Clin Transplant 2000;14:386. [8] Gastaca M, Valdivieso A, Pijoa J. Donors older than 70 years in liver transplantation. Transplant Proc 2005;37:3851.