EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: Multiorgan procurement involving thoracic organs prolongs the liver recovery cross-clamp time. This may impact the outcome of hepatic allograft, more so in older donors (age > 60 years). We compared the outcomes of liver allografts from older donors with and without recovery of thoracic organs.

Materials and Methods: Using the Scientific Registry of Transplant Recipients database, we compared survival outcomes of 258 adults who received a liver allograft from older donors with thoracic organ recovery (group A) with 6006 patients who received liver allografts from older donor without thoracic organ recovery (group B). Furthermore, we performed a subgroup analysis matched for recipient and donor risk factors including presence of hypertension, diabetes mellitus, renal function, donor age, and use of inotropes. For the final analyses, there were 159 patients in group A and 468 in group B.

Results: The 1-month, 1-year, 3-year, and 5-year patient survival rates in group A were 95%, 91.6%, 70.1%, and 65.5% compared with 95%, 92%, 70%, and 57.7% in group B, respectively (P = .695). Graft survival rates for group A at the same time points were 91.5%, 81.0%, 71.7%, and 57.4% compared with 91.3%, 81.1%, 61.9%, and 50.4% in group B, respectively (P = .791). In the matched population, patient survival rates at 1 month, 1 year, 3 years, and 5 years were 95%, 83.1%, 77.1%, and 68.8% compared with 94.4%, 81.6%, 72.2%, and 66.8% in group B, respectively (P = .69). Graft survival rates at the same time points were 88.7%, 76.8%, 71.5%, and 63.1% in group A and 90.0%, 77.5%, 70.4%, and 62.5% in group B, respectively (P = .956).

Conclusions: Liver procurement with or without recovery of thoracic organs from donors > 60 years old does not affect liver grafts and recipient outcomes in the short-term or long-term and should be encouraged.

Key words : Graft and patient survival posttransplant, Multiorgan procurement, Scientific Registry of Transplant Recipients, United Network for Organ Sharing

There has been a steady increase in demand for solid-organ transplants in the past 2 decades.^1,2 However, the donor pool has largely remained stagnant. To decrease wait list time and mortality for liver and thoracic organ transplants, the number of older candidates selected as donors is increasing.^3,4 Several reports have suggested that survival outcomes for recipients of thoracic organs and livers are similar compared with younger donors, although many authors have suggested that these improvements may be the result of a higher level of care and consideration during the process of donor selection and recipient matching.^5-9 With a shortage of donor organs, the selection of older donors is more prevalent than in the past. Simultaneous procurements of thoracic organ(s) from older donors have been reported, to increase the donor pool. It is postulated that the increase in cross-clamp time for liver recovery during simultaneous thoracic organ procurement could potentially worsen recipient and/or graft outcomes, more so when older donors are used. The increase in cross-clamp time could lead to primary nonfunction and may result an increase in the rate of 30-day retransplant or mortality^5-7 or cholangiopathy in the long-term. After a comprehensive literature survey, we found no previously published studies on survival outcomes of liver transplant recipients who had received livers from older donors with simultaneous recovery of thoracic organs.

In this study, we compared survival rates for recipient and grafts for liver transplants from older donors (age > 60 years) when the liver was procured with (group A) or without simultaneous procurement of thoracic organs (group B).

Materials and Methods

We reviewed the United Network for Organ Sharing (UNOS) database from 1987 to 2010 after obtaining approval from the Institutional Review Board.⁵ The data included all liver recoveries from donors in the United States. The study population was divided into 2 groups. Group A consisted of simultaneous abdominal and thoracic organs procurement, and group B included procurement of abdominal organs only. Recipient survival, graft survival, and the rates of retransplant in both groups were calculated.

There was a total of 6322 older donors (age > 60 years) selected during the study period. There were 60 donors with inadequate data, and they were excluded from the study. Available cases for the study were divided into 2 groups. Group A (study group) included 258 recipients who had received livers from deceased donors with simultaneous thoracic organ recovery. Group B (control group) included 6006 recipients who had received livers from abdominal organ donors only. The demographic data for donors and recipients are presented in Tables 1 and 2, respectively. We accounted for the differences in donor and recipient risk factors and matched 159 donors from group A to 468 donors from group B for all variables (Table 3). The matched population data from groups A and B were then analyzed. All patients were followed up for a mean duration of 5 years. All of the donors were deceased.

Statistical analyses
All data are presented as mean values with standard deviation (SD). We performed comparisons of mean with 2-tailed t tests for continuous variables and with the Pearson chi-square test for categorical variables. We used the Kaplan-Meier method to estimate patient and graft survival, and we used the log-rank test (SPSS, version 25.0; SPSS, Inc.) to compare survival differences in the 2 groups. P < .05 was considered significant.

The recipient demographics are shown in Table 2. There were 254 older donors (4.12%) who were used for combined thoracic organ and liver recoveries. The overall patient survival rates at 1 month, 1 year, 3 years, and 5 years in group A were 95.%, 91.6%, 70.1%, and 65.5% compared with 95%, 92%, 70%, and 57.7% in group B, respectively (P = .695) (Figure 1). Also, graft survival rates at identical time points for group A were 91.5%, 81.0%, 71.7%, and 57.4% and for group B were 91.3%, 81.1%, 61.9%, and 50.4%, respectively (P = .791) (Figure 2).

Although the overall recipient and graft survival rates in both groups were not statistically different, we did observe an apparent difference in survival at 5 years. The patient survival rate was 7.8% lower and the graft survival rate was 7.3% lower in group B compared with group A. All donors were > 60 years old in both groups. On detailed examination of demographics, we found significant differences in the risk factors between groups A and B. The mean values for donor age and for number of donors > 65 years old were significantly higher in group B. Mean serum creatinine values were higher in group B but did not reach statistical significance (P = .078). Also, rates of hypertension and diabetes mellitus were significantly higher in group B. In group A, the need for inotropes was significantly higher (Table 1). The differences between the donor and recipient characteristics in groups A and B were compatible. Therefore, the 159 donors from group A were matched for all the variables with the 468 donors in group B (Table 3). This matched population was then reexamined with regard to patient and graft survival.

The patient survival rates for the matched population in group A at 1 month, 1 year, 3 years, and 5 years were 95%, 83.1%, 77.1%, and 68.8% compared with 94.4%, 81.6%, 72.2%, and 66.8% in group B, respectively (P = .69) (Figure 3). Graft survival rates at 1 month, 1 year, 3 years, and 5 years were 88.7%, 76.8%, 71.5%, and 63.1% in group A and 90.0%, 77.5%, 68.4%, and 62.5% in group B, respectively (P = .956) (Figure 4). In the matched population, recipient and graft survival rates were almost identical, at each time point.

There is a growing disparity between the supply and demand for organs for transplant. The past 3 decades have shown that the annual rate of solid-organ transplant exceeds the annual rate of deceased donor organ donation.⁵

In 2000, we reported 4000 consecutive liver transplants from a single center between 1981 and 1998. We observed that organ donation rates from donors > 50 years old had increased from 6% between years 1981 and 1985 to 11% between years 1986 and 1990. There was a further increase to 21% between 1990 and 1998.10 Since 1988, the UNOS database has shown a rising trend of organ use from older donors.^3,5 Multiple studies have also suggested successful use of older donors for liver, heart, and lung transplants.

In a review of literature for liver transplantation, Neipp and colleagues reported on 1208 transplants between 1990 and 2002.¹¹ There were 67 donors who were > 60 years old and had outcomes similar to younger donors. Macedo and colleagues observed worse outcome from donors > 50 years old.¹²They suggested closer monitoring of recipients when older donors are selected. Sampedro and colleagues showed similar outcomes for donors > 75 years old (n = 24) compared with donors < 75 years old (n = 174).¹³ The operative time was longer in older donors, and the authors suggest that careful donor selection may reduce recipient mortality and morbidity. Faber and colleagues examined 272 liver transplant recipients and divided the donors into the following age groups: < 50 years, from 50 to 59 years, from 60 to 69 years, and ≥ 70 years.⁷ They concluded similar rates of survival for patients and grafts; however, ischemic biliary lesion rates were significantly higher with donors ≥ 70 years old.7 Chapman and colleagues reported on 1036 adult recipients and showed comparable outcomes in graft and patient survival from donors ≥ 60 years old, regardless of recipient age, without an increase in complication rate.14 Bertuzzo and colleagues, in a single-center European study, concluded that the outcomes from liver donors > 70 years old were comparable, with appropriate donor management.¹⁵

In a review of literature for heart transplant, Bennett and colleagues reported a higher relative risk of survival with donors > 50 years old; however, mortality risk without transplant was even higher.¹⁶ Loebe and colleagues compared 167 recipients of organs from donors > 50 years old with 524 recipients of organs from donors < 35 years old and with 379 recipients of organs from donors 35 to 50 years old.⁸ They found no significant difference at midterm follow-up. Blanche and colleagues reported survival rates after heart transplant from donors > 50 years old were no different from donors < 50 years old (N = 267).⁶ However, older donors were carefully selected in this study. Macedo and colleagues in 2010 reported contradictory findings, with lower rates for patient and graft survival from donors > 50 years old.¹² They concluded that older recipients needed younger donors and recommended more robust follow-up for the first 18 months after heart transplant. Daniel and colleagues reported similar conclusions, with higher mortality in donors > 50 years old and recipients > 60 years old.¹⁷

For lung transplantation, DuBose and Salim suggested aggressive donor management to bridge the gap between organ supply and organ demand.¹⁸ Shigemura and colleagues reported a single-center experience with 593 lung transplants that included 87 of donors > 55 years old (14.7%).⁹ The outcomes were comparable with outcomes in younger donors < 55 years old. They observed increased mortality in transplants from older donors to older recipients with pulmonary hypertension or those requiring lung-cardiopulmonary bypass. However, they observed that donor age > 55 years should not be an exclusion criteria.⁹ They concluded that careful recipient selection criteria and meticulous surgical planning is required to improve outcomes.

We reviewed the UNOS national database for all organ transplantation from 1988 onward and investigated trends during the past 30 years.5 For liver recipients, the number of elected donors 50 to 64 years old has increased from 13.8% in 1990 to 24.4% in 2020. Simultaneously, the number of selected donors who were ≥ 65 years old has increased from 1.8% in 1990 to 7.7% in 2020. Similarly, for heart recipients, the number of selected donors between 50 and 60 years old has increased from 3.7% in 1990 to 9.5% in 2000; however, there has been a small decrease to 7.4% in 2020. For heart donors ≥ 65 years old, the rate of donation has been 0.16% during the past 20 years. Interestingly, for lung recipients, the rate of donation for donors 50 to 64 years old was 1.8% in 1990 with an increase to 10.5% in 2000, 15.8% in 2010, and 15.0% in 2020, thus far. For lung recipients, donors ≥ 65 years old, continues to remain low (albeit, slightly better than for heart recipients) and accounts for 1.2% of lung transplants in the past 20 years (Figure 5).

There is sufficient evidence to support the use of older donors for liver, heart, and lung transplants. Thoracic organ procurement prolongs the cross-clamp time and may adversely affect liver outcomes when the liver is simultaneously recovered. However, to date, the data regarding simultaneous liver and thoracic organ procurement from older donors are scant.

In the present study, we have shown that in well-matched recipients and donors, the recipient and graft survival rates after liver transplant are comparable with those with and without simultaneous thoracic organ procurement.

From 1987 to 2010, less than 9% of the donors between the ages of 60 and 65 years were selected for combined thoracic and abdominal organ procurement. Our study shows that use of liver allografts from donors > 60 years old with or without simultaneous thoracic organ procurement has no effect on short-term or long-term and recipient or graft survival outcomes. Furthermore, survival outcomes were no different when donor characteristics were matched for age, presence of diabetes mellitus, hypertension, use of inotropes, and renal function. We conclude that procurement of thoracic organs with or without liver from donors > 60 years old does not affect long-term or short-term and liver graft or recipient outcomes and should be encouraged.

Volume: 18 Issue: 7 December 2020

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