Assessment of Trends in Transplantation of Liver Grafts From Older Donors and Outcomes in Recipients of Liver Grafts From Older Donors, 2003-2016 | Gastrointestinal Surgery | JAMA Surgery | JAMA Network
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Figure 1.  Discarded Liver Grafts From Older Donors and Younger Donors by Year of Liver Graft Recovered and Relative Odds of Liver Graft Discard From Older Donors by Organ Procurement Organization Compared With the National Average
Discarded Liver Grafts From Older Donors and Younger Donors by Year of Liver Graft Recovered and Relative Odds of Liver Graft Discard From Older Donors by Organ Procurement Organization Compared With the National Average

A, Percentages were adjusted for sex, race/ethnicity, body mass index, donor cause of death, donation after cardiac death, and hepatitis C virus status after accounting for Organ Procurement Organization level variation. B, Markers represent the relative risk, with whiskers indicating 95% CIs.

Figure 2.  Recipients of Liver Grafts From Older Donors by Year of Liver Transplant
Recipients of Liver Grafts From Older Donors by Year of Liver Transplant

Dashed line indicates the percentage of liver grafts from older donors among all adult liver transplant recipients.

Figure 3.  Cumulative Incidence of Mortality and All-Cause Graft Loss
Cumulative Incidence of Mortality and All-Cause Graft Loss

The most recent time periods were split at June 18, 2013, after the allocation policy implementation of Share 35.24

Table 1.  Characteristics of 4127 Recovered and 747 Discarded Liver Grafts From Older Donors (2003–2016)
Characteristics of 4127 Recovered and 747 Discarded Liver Grafts From Older Donors (2003–2016)
Table 2.  Characteristics of Recipients of Liver Grafts From Older Donors (2003-2016)
Characteristics of Recipients of Liver Grafts From Older Donors (2003-2016)
1.
Israni  AK, Zaun  D, Rosendale  JD, Schaffhausen  C, Snyder  JJ, Kasiske  BL.  OPTN/SRTR 2016 annual data report: deceased organ donation.  Am J Transplant. 2018;18(suppl 1):434-463. doi:10.1111/ajt.14563PubMedGoogle ScholarCrossref
2.
Kim  WR, Lake  JR, Smith  JM,  et al.  OPTN/SRTR 2015 annual data report: liver.  Am J Transplant. 2017;17(suppl 1):174-251. doi:10.1111/ajt.14126PubMedGoogle ScholarCrossref
3.
Pondrom  S.  White House holds summit on organ transplantation.  Am J Transplant. 2016;16(8):2241-2242. doi:10.1111/ajt.13942PubMedGoogle ScholarCrossref
4.
Pruett  TL, Chandraker  A.  The White House Organ Summit: what it means for our field.  Am J Transplant. 2016;16(8):2245-2246. doi:10.1111/ajt.13947PubMedGoogle ScholarCrossref
5.
Alexander  JW, Vaughn  WK.  The use of “marginal” donors for organ transplantation. The influence of donor age on outcome.  Transplantation. 1991;51(1):135-141. doi:10.1097/00007890-199101000-00021PubMedGoogle ScholarCrossref
6.
Alexander  JW, Vaughn  WK, Carey  MA.  The use of marginal donors for organ transplantation: the older and younger donors.  Transplant Proc. 1991;23(1 pt 2):905-909.PubMedGoogle Scholar
7.
Busuttil  RW, Tanaka  K.  The utility of marginal donors in liver transplantation.  Liver Transpl. 2003;9(7):651-663. doi:10.1053/jlts.2003.50105PubMedGoogle ScholarCrossref
8.
Statistical Abstract of the United States: 2010. US Census Bureau 2012. https://www.census.gov/library/publications/2011/compendia/statab/131ed.html. Accessed August 1, 2018.
9.
Montenovo  MI, Hansen  RN, Dick  AA, Reyes J.  Donor age still matters in liver transplant: results From the United Network for Organ Sharing-Scientific Registry of Transplant Recipients database.  Exp Clin Transplant. 2017;15(5):536-541.PubMedGoogle Scholar
10.
Stewart  ZA, Locke  JE, Segev  DL,  et al.  Increased risk of graft loss from hepatic artery thrombosis after liver transplantation with older donors.  Liver Transpl. 2009;15(12):1688-1695. doi:10.1002/lt.21946PubMedGoogle ScholarCrossref
11.
Feng  S, Goodrich  NP, Bragg-Gresham  JL,  et al.  Characteristics associated with liver graft failure: the concept of a donor risk index.  Am J Transplant. 2006;6(4):783-790. doi:10.1111/j.1600-6143.2006.01242.xPubMedGoogle ScholarCrossref
12.
Reese  PP, Sonawane  SB, Thomasson  A, Yeh  H, Markmann  JF.  Donor age and cold ischemia interact to produce inferior 90-day liver allograft survival.  Transplantation. 2008;85(12):1737-1744. doi:10.1097/TP.0b013e3181722f75PubMedGoogle ScholarCrossref
13.
Sayuk  GS, Leet  TL, Schnitzler  MA, Hayashi  PH.  Nontransplantation of livers from deceased donors who are able to donate another solid organ: how often and why it happens.  Am J Transplant. 2007;7(1):151-160. doi:10.1111/j.1600-6143.2006.01600.xPubMedGoogle ScholarCrossref
14.
Paterno  F, Wima  K, Hoehn  RS,  et al.  Use of elderly allografts in liver transplantation.  Transplantation. 2016;100(1):153-158. doi:10.1097/TP.0000000000000806PubMedGoogle ScholarCrossref
15.
Croome  KP, Lee  DD, Keaveny  AP, Taner CB.  Noneligible donors as a strategy to decrease the organ shortage.  Am J Transplant. 2017;17(6):1649-1655. doi:10.1111/ajt.14163PubMedGoogle Scholar
16.
Barbier  L, Cesaretti  M, Dondero  F,  et al.  Liver transplantation with older donors: a comparison with younger donors in a context of organ shortage.  Transplantation. 2016;100(11):2410-2415. doi:10.1097/TP.0000000000001401PubMedGoogle ScholarCrossref
17.
Bertuzzo  VR, Cescon  M, Odaldi  F,  et al.  Actual risk of using very aged donors for unselected liver transplant candidates: a European single-center experience in the MELD era.  Ann Surg. 2017;265(2):388-396. doi:10.1097/SLA.0000000000001681PubMedGoogle ScholarCrossref
18.
Halazun  KJ, Quillin  RC, Rosenblatt  R,  et al.  Expanding the margins: high volume utilization of marginal liver grafts among >2000 liver transplants at a single institution.  Ann Surg. 2017;266(3):441-449. doi:10.1097/SLA.0000000000002383PubMedGoogle ScholarCrossref
19.
Ghinolfi  D, Marti  J, De Simone  P,  et al.  Use of octogenarian donors for liver transplantation: a survival analysis.  Am J Transplant. 2014;14(9):2062-2071. doi:10.1111/ajt.12843PubMedGoogle ScholarCrossref
20.
Su  F, Yu  L, Berry  K,  et al.  Aging of liver transplant registrants and recipients: trends and impact on waitlist outcomes, post-transplantation outcomes, and transplant-related survival benefit.  Gastroenterology. 2016;150(2):441-53.e6. doi:10.1053/j.gastro.2015.10.043PubMedGoogle ScholarCrossref
21.
United Network for Organ Sharing Reports. Deceased Donors Recovered in the United States by Donor Age, 2016. https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/#. Accessed August 1, 2018.
22.
Orman  ES, Barritt  AS  IV, Wheeler  SB, Hayashi  PH.  Declining liver utilization for transplantation in the United States and the impact of donation after cardiac death.  Liver Transpl. 2013;19(1):59-68. doi:10.1002/lt.23547PubMedGoogle ScholarCrossref
23.
Goldberg  D, Ditah  IC, Saeian  K,  et al.  Changes in the prevalence of hepatitis C virus infection, nonalcoholic steatohepatitis, and alcoholic liver disease among patients with cirrhosis or liver failure on the waitlist for liver transplantation.  Gastroenterology. 2017;152(5):1090-1099.e1. doi:10.1053/j.gastro.2017.01.003PubMedGoogle ScholarCrossref
24.
Organ Procurement and Transplantation Network. https://optn.transplant.hrsa.gov/media/1200/optn_policies.pdf#nameddest=Policy_09. Accessed January 4, 2019.
25.
Massie  AB, Kucirka  LM, Segev  DL.  Big data in organ transplantation: registries and administrative claims  [published correction appears in Am J Transplant. 2014;14(11):2673].  Am J Transplant. 2014;14(8):1723-1730. doi:10.1111/ajt.12777PubMedGoogle ScholarCrossref
26.
Louis  TA, Zeger  SL.  Effective communication of standard errors and confidence intervals.  Biostatistics. 2009;10(1):1-2. doi:10.1093/biostatistics/kxn014PubMedGoogle ScholarCrossref
27.
Orman  ES, Mayorga  ME, Wheeler  SB,  et al.  Declining liver graft quality threatens the future of liver transplantation in the United States.  Liver Transpl. 2015;21(8):1040-1050. doi:10.1002/lt.24160PubMedGoogle ScholarCrossref
28.
Halazun  KJ, Rana  AA, Fortune  B,  et al.  No country for old livers? examining and optimizing the utilization of elderly liver grafts.  Am J Transplant. 2018;18(3):669-678. doi:10.1111/ajt.14518PubMedGoogle Scholar
29.
Segev  DL, Maley  WR, Simpkins  CE,  et al.  Minimizing risk associated with elderly liver donors by matching to preferred recipients.  Hepatology. 2007;46(6):1907-1918. doi:10.1002/hep.21888PubMedGoogle ScholarCrossref
30.
Haugen  CE, Thomas  AG, Garonzik-Wang  J, Massie  AB, Segev  DL.  Minimizing risk associated with older liver donors by matching to preferred recipients: a national registry and validation study.  Transplantation. 2018;102(9):1514-1519. doi:10.1097/TP.0000000000002190PubMedGoogle ScholarCrossref
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    Original Investigation
    February 13, 2019

    Assessment of Trends in Transplantation of Liver Grafts From Older Donors and Outcomes in Recipients of Liver Grafts From Older Donors, 2003-2016

    Author Affiliations
    • 1Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
    • 2Department of Surgery, University of California, San Francisco
    • 3Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland
    • 4Scientific Registry of Transplant Recipients, Minneapolis, Minnesota
    JAMA Surg. 2019;154(5):441-449. doi:10.1001/jamasurg.2018.5568
    Key Points

    Question  What were the trends in use of liver grafts from older donors (aged ≥70 years) and outcomes in liver-only transplant recipients of older donor grafts in the United States from 2003 to 2016?

    Findings  In this cohort study of 4127 liver grafts from older donors and 3350 liver-only recipients of older donor grafts, and 78 990 liver grafts from younger donors (aged 18-69 years) and 64 907 liver-only recipients of younger donor grafts, there was a decrease in the use of liver grafts from older donors despite significant improvements in all-cause graft loss and mortality among liver transplant recipients of older donor grafts. These posttransplant improvements are more substantial than those seen in recipients of younger donor grafts.

    Meaning  These findings suggest that clinicians should consider more liberal and broader use of liver grafts from older donors to expand the potential donor pool.

    Abstract

    Importance  In light of the growing population of older adults in the United States, older donors (aged ≥70 years) represent an expansion of the donor pool; however, their organs are underused. Liver grafts from older donors were historically associated with poor outcomes and higher discard rates, but clinical protocols, organ allocation, and the donor pool have changed in the past 15 years.

    Objective  To evaluate trends in demographics, discard rates, and outcomes among older liver donors and transplant recipients of livers from older donors in a large national cohort.

    Design, Setting, and Participants  Prospective cohort study of 4127 liver grafts from older donors and 3350 liver-only recipients of older donor grafts and 78 990 liver grafts from younger donors (aged 18-69 years) and 64 907 liver-only recipients of younger donor grafts between January 1, 2003, and December 31, 2016, in the United States. The Scientific Registry of Transplant Recipients, which includes data on all transplant recipients in the United States that are submitted by members of the Organ Procurement and Transplantation Network, was used.

    Exposures  Year of liver transplant and age of liver donor.

    Main Outcomes and Measures  Odds of graft discard and posttransplant outcomes of all-cause graft loss and mortality.

    Results  In this study, 4127 liver grafts from older donors were recovered for liver transplant across the study period (2003-2016); 747 liver grafts from older donors were discarded, and 3350 liver grafts from older donors were used for liver-only recipients. After adjusting for donor characteristics other than age and accounting for Organ Procurement Organization–level variation, liver grafts from older donors were more likely to be discarded compared with liver grafts from younger donors in 2003-2006 (adjusted odds ratio [aOR], 1.97; 95% CI, 1.68-2.31), 2007-2009 (aOR, 2.55; 95% CI, 2.17-3.01), 2010-2013 (aOR, 2.04; 95% CI, 1.68-2.46), and 2013-2016 (aOR, 2.37; 95% CI, 1.96-2.86) (P < .001 for all). Transplants of liver grafts from older donors represented a progressively lower proportion of all adult liver transplants, from 6.0% (n = 258 recipients) in 2003 to 3.2% (n = 211 recipients) in 2016 (P = .001). However, outcomes in recipients of grafts from older donors improved over time, with 40% lower graft loss risk (adjusted hazard ratio, 0.60; 95% CI, 0.53-0.68; P < .001) and 41% lower mortality risk (adjusted hazard ratio, 0.59; 95% CI, 0.52-0.68; P < .001) in 2010 through 2016 vs 2003 through 2009; these results were beyond the general temporal improvements in graft loss (interaction P = .03) and mortality risk (interaction P = .04) among recipients of liver grafts from younger donors.

    Conclusions and Relevance  These findings show that from 2003 to 2016, liver graft loss and mortality among recipients of liver grafts from older donors improved; however, liver graft discard from older donors remained increased and the number of transplants performed with liver grafts from older donors decreased. Expansion of the donor pool through broader use of liver grafts from older donors might be reasonable.

    Introduction

    More than 14 000 patients are presently on the waiting list in the United States for liver transplants, but only 8082 liver transplant were performed in 2017.1 Each year more than 10% of waiting list candidates die waiting for a liver transplant,2 thus the shortage of donors is a significant public health problem.3,4 The disparity between the number of available donors and the demand for livers by waiting list candidates has motivated development of novel ways to expand the donor pool. One controversial approach that has been cautiously used during the past 3 decades is the use of livers from older donors.5-7 This potential donor pool is becoming increasingly more relevant and timely because nearly 15% of the US population is projected to be older than 70 years by 2030.8 With continued attention to the use of liver grafts from older donors and the present shortage of donors, use of liver grafts from older donors has likely evolved. A description of the temporal trends in liver graft discard and recipient outcomes from older donors could inform clinical decision making and the expansion of this potential donor pool.

    Liver grafts from older donors have historically been associated with graft loss and recipient mortality, which has led to the reluctance of clinicians to transplant these organs.9-13 For this reason, grafts from older donors accounted for only 4.3% of all liver grafts from 2007 through 2011,14 with substantial center-level variation in transplants, ranging from 0% to 33% of all transplanted grafts.15 Although several single-center studies16-19 reported more routine use of livers from older donors and showed similar graft and patient survival regardless of donor age, these studies were limited by small sample size. Furthermore, a more current exploration of national changes in liver grafts from older donors is necessary because use of grafts from older donors and recipient outcomes have likely changed with evolving donor and recipient demographics (increasing age of recipients20 and donors,21,22 and indication for liver transplants20,23), treatment for hepatitis C virus with direct-acting antiviral medications, and changes in liver allocation policy (eg, Share 3524 and exception points for hepatocellular carcinoma).

    We used national registry data from the Scientific Registry of Transplant Recipients to (1) quantify trends in the discard and use of liver grafts from older donors, (2) quantify Organ Procurement Organization (OPO)–level variation in discard of liver grafts from older donors, (3) characterize the changing landscape (donor, recipient, and policy changes) of these grafts and their recipients, and (4) describe trends in graft loss and mortality among liver-only recipients from older donors from 2003 to 2016. We also compared trends in liver graft discard and posttransplant outcomes between older and younger donors.

    Methods
    Data Source

    This study used data from the Scientific Registry of Transplant Recipients with available follow-up through March 2017. The registry includes data about all donors, wait-listed candidates, and transplant recipients in the United States that are submitted by members of the Organ Procurement and Transplantation Network and has been described elsewhere.25 Mortality and graft loss were augmented through linkage of the registry with the Social Security Master Death File, data from Centers for Medicare & Medicaid Services, and waiting list data. The Health Resources and Services Administration, an agency of the US Department of Health and Human Services, provides oversight to the activities of Organ Procurement and Transplantation Network and Scientific Registry of Transplant Recipients contractors. This study was approved by the Johns Hopkins Medicine institutional review board with patient consent waived because the study was acknowledged as nonhuman research.

    Study Population

    We identified 4127 liver grafts from older donors (aged ≥70 years) recovered for transplant and 3350 deceased donor liver-only recipients of grafts from older donors (aged ≥70 years) between January 1, 2003, and December 31, 2016. We also identified 78 990 liver grafts from younger donors (aged 18-69 years) recovered for transplant and 64 907 deceased donor liver-only recipients of grafts from younger donors (aged 18-69 years) in the same period. We empirically grouped recipients into 4 strata (2003-2006, 2007-2009, 2010-2013 [2010 to June 18, 2013], and 2013-2016 [June 18, 2013, to 2016]) to reflect changes in allocation policy and general evolution of immunosuppression regimens. We divided the 2 recent periods at June 18, 2013, to evaluate trends before and after implementation of the Share 3524 policy change, which increased regional sharing of liver allograft offers to patients with a Model for End-stage Liver Disease (MELD) score of 35 or higher. The calculated MELD score is reported as the laboratory MELD score at the time of transplant. The allocation MELD score is reported as the allocation score at the time of transplant. Recipients with missing data about body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) (2121 of 68 257 recipients; 3.1%) and cold ischemia time (defined as time from organ cooling to rewarming at transplant) (2575 of 68 257 recipients; 3.8%) were excluded from the analysis.

    Liver Graft Discard Over Time

    We estimated the percentage of liver graft discard (defined as recovered but not transplanted liver grafts) according to donor age in each time stratum. To characterize the change in liver graft discard, we performed a multilevel logistic regression model with an interaction between donor age and time stratum. This model also accounted for underlying variation across OPOs. All models were adjusted for donor cause of death, sex, race/ethnicity, donation after cardiac death, and hepatitis C virus.

    Variation in Liver Graft Discard Across OPOs

    To characterize the variation in liver graft discard across OPOs, we performed a multilevel logistic regression model among only liver grafts from older donors and calculated each OPO’s individual rate of liver graft discard from older donors, adjusted for donor race/ethnicity, sex, BMI, hepatitis C virus, donor cause of death, and donation after cardiac death. The interclass correlation coefficient from this model quantified the variance in liver graft discard explained by the OPO where the graft was recovered. We calculated the odds that a liver graft from an older donor was discarded for each OPO. From this model, we derived the national average odds of discard and the odds of discard at the highest–graft using OPOs (lowest quartile of liver graft discard). We then estimated the number of liver grafts from older donors that would not have been discarded if all OPOs discarded at or below the national average and separately if all OPOs discarded at or below the lowest quartile. In other words, we determined the number of additional liver grafts from older donors that would have been used for transplant if they were discarded at rates observed in high–graft using OPOs.

    Recipients of Liver Grafts From Older Donors

    We calculated the percentage of adult recipients of liver transplants who received liver grafts from older donors annually during the study period. The Cuzick test of trend was used to compare changes in the number of recipients of liver grafts from older donors during the study period. We compared characteristics of the recipient, donor, and transplant among recipients of liver grafts from older donors for each time stratum.

    Mortality and All-Cause Graft Loss in Recipients of Liver Grafts From Older Donors

    Mortality and all-cause graft loss were estimated at 1, 3, and 5 years using the Kaplan-Meier method for each time stratum. The Kaplan-Meier method was also used to create unadjusted cumulative incidence curves of mortality and all-cause graft loss for each time stratum. Cox proportional hazards models for mortality and all-cause graft loss were adjusted for recipient factors (sex, age, race/ethnicity, BMI, primary diagnosis, MELD score, life support before liver transplant, hepatocellular carcinoma, hepatitis C virus, HIV, diabetes, primary insurance, and portal vein thrombosis), donor factors (race/ethnicity, BMI, hepatitis C virus, and donation after cardiac death), and transplant factors (cold ischemia time and shared organ status). To test whether temporal trends in mortality and all-cause graft loss differed between liver donor age groups, interactions between donor age (older vs younger donors) and each outcome were explored. For all models, proportional hazards assumptions were confirmed with visual inspection of complementary log-log plots and Schoenfeld residuals.

    Statistical Analyses

    Continuous variables were compared using t tests, and categorical variables were compared using χ2 tests. Race/ethnicity was reported by clinicians to the Organ Procurement and Transplantation Network, and CIs were reported according to the method of Louis and Zeger.26 All analyses were 2-tailed, and α was set at .05 to indicate statistical significance. All analyses were performed using Stata, version 14.2/MP (StataCorp).

    Results
    Liver Grafts From Older Donors

    Among 4127 liver grafts from older donors that were recovered for liver transplant across the entire study period (2003-2016), 2241 donors (54.3%) were aged 70 to 74 years, 1361 (33.0%) were aged 75 to 79 years, 435 (10.5%) were aged 80 to 84 years, and 90 (2.2%) were 85 years or older (Table 1). Among 747 discarded liver grafts from older donors, 381 donors (51.0%) were aged 70 to 74 years, 246 (32.9%) were aged 75 to 79 years, 98 (13.1%) were aged 80 to 84 years, and 22 (2.9%) were 85 years or older (Table 1). Among 3350 liver grafts from older donors for liver-only recipients, 1838 (54.9%) were aged 70 to 74 years, 1109 (33.1%) were aged 75 to 79 years, 335 (10.0%) were aged 80 to 84 years, and 68 (2.0%) were 85 years or older.

    Characteristics of Donors of Recovered and Discarded Livers

    The mean (SD) BMI of older donors of recovered liver grafts increased from 26.1 (5.0) during 2003 through 2006 to 28.0 (5.9) during 2013 through 2016 (P < .001). Recent older donors were less likely to be white (633 of 905 [69.9%] in 2013-2016 vs 1112 of 1379 [80.6%] in 2003-2006; P < .001) and were less likely to have grafts donated after cardiac death (1 of 905 [0.1%] in 2013-2016 vs 9 of 1379 [0.7%] in 2003-2006; P = .008) (Table 1). Quiz Ref IDSimilarly, the mean (SD) BMI of donors of discarded liver grafts increased from 26.7 (5.3) during 2003 through 2006 to 28.7 (6.3) during 2013 through 2016 (P = .008). Recently discarded liver grafts were less likely to be from white donors (112 of 152 [73.7%] in 2013-2016 vs 177 of 219 [80.8%] in 2003-2006; P = .03) (Table 1).

    Liver Graft Discard From Older Donors

    Quiz Ref IDLiver graft discard from older donors increased from 34 livers (11.6%) in 2003, peaked at 76 (24.5%) in 2008, and decreased to (but still higher than 2003) 38 (15.4%) in 2016; graft discard from older donors was higher every year in the study period compared with graft discard from younger donors (34 of 293 [11.6%] vs 357 of 4461 [8.0%] in 2003, 76 of 310 [24.5%] vs 646 of 5548 [13.1%] in 2008, and 38 of 249 [15.4%] vs 657 of 7031 [9.3%] in 2016) (Figure 1A). After adjustment, grafts from older donors were more than twice as likely to be discarded compared with grafts from younger donors from 2003 through 2006 (adjusted odds ratio [aOR], 1.97; 95% CI, 1.68-2.31), 2007-2009 (aOR, 2.55; 95% CI, 2.17-3.01), 2010-2013 (aOR, 2.04; 95% CI, 1.68-2.46), and 2013-2016 (aOR, 2.37; 95% CI, 1.96-2.86) (P < .001 for all).

    Liver Graft Discard From Older Donors Across OPOs

    Among the 58 OPOs in the United States, liver graft discard from older donors ranged from 0% to 35.3%, with a median graft discard of 15.1% (interquartile range, 9.8%-25.0%). This variation in graft discard was significant across OPOs (likelihood ratio test, P < .001). However, the interclass correlation coefficient was 0.057, meaning that only 5.7% of the variation in graft discard was associated with OPO (Figure 1B). The OPO-specific ORs of liver graft discard ranged from 0.31 (95% CI, 0.17-0.58) to 2.69 (95% CI, 2.20-3.29); 4 of 58 OPOs (6.9%) had statistically significantly higher ORs and 4 had statistically significantly lower ORs of liver graft discard compared with the national average. (Centers are compared with the national average of 1. Result <1 is below the national average and result >1 is above the national average.) (Figure 1B). Quiz Ref IDIf all OPOs discarded grafts from older donors at or below the 25th percentile of discard, 277 more grafts would have been used, a 34% reduction. If all OPOs discarded grafts at or below the national average, 177 more grafts would have been used, a 24% reduction.

    Recipients of Liver Grafts From Older Donors

    The mean (SD) age of the 3350 recipients of liver grafts from older donors was 57.6 (9.4) years; 1260 (37.6%) were women, and 2473 (73.8%) were white (Table 2). The mean (SD) calculated MELD score was 19 (8) at the time of liver transplant. Indications for transplant were alcoholic cirrhosis (711 of 3350 [21.2%]), hepatitis C virus (458 [13.7%]), hepatocellular carcinoma (623 [18.6%]), nonalcoholic steatohepatitis (336 [10.0%]), primary biliary cirrhosis (169 [5.0%]), and primary sclerosing cholangitis (168 [5.0%]).

    Characteristics of Recipients of Liver Grafts From Older Donors

    The number of recipients of liver grafts from older donors steadily decreased from 258 in 2003 to 211 in 2016 (Figure 2) and the percentage among all adult liver recipients decreased from 6.0% to 3.2% (P = .001). The mean (SD) age increased from 55.9 (9.7) years in 2003 to 59.8 (8.5) years in 2016 (P < .001). Among 747 recipients of liver grafts from older donors from 2013 through 2016 vs 1147 recipients from 2003 through 2006, female sex (287 [38.4%] vs 433 [37.9%]; P = .94), mean (SD) BMI (28.1 [5.4] vs 28.2 [7.4]; P = .07), and white race/ethnicity (545 [73.0%] vs 887 [74.6%]; P = .26) did not differ significantly. The mean (SD) calculated MELD score at the time of liver transplant did not change (18 [8] in 2013-2016 vs 18 [8] in 2003-2006; P = .80), but the mean (SD) allocation MELD score increased (25 [6] vs 21 [7]; P < .001). Recent recipients of livers from older donors were more likely to have nonalcoholic steatohepatitis (126 [16.9%] in 2013-2016 vs 47 [4.1%] in 2003-2006) or hepatocellular carcinoma (169 [22.6%] vs 123 [10.6%]) and less likely to have hepatitis C virus (86 [11.5%] vs 227 [20.0%]) as the primary indication for liver transplant (P < .001 for all) (Table 2).

    Mortality Among Recipients of Liver Grafts From Older Donors

    Mortality among recipients from older and younger donors improved after liver transplant (Figure 3A and C). Quiz Ref IDAmong recipients of liver grafts from older donors from 2003 through 2009 to 2010 through 2016, 1-year mortality improved from 18% to 11%, 3-year from 28% to 18%, and 5-year from 37% to 23%. Among recipients of liver grafts from younger donors, 1-year mortality improved from 13% to 11%, 3-year from 22% to 14%, and 5-year from 28% to 21%. The improvements in mortality were greater among recipients of liver grafts from older donors (P = .04 for interaction) (Figure 3C). From 2010 through 2016, recipients of liver grafts from older donors were at a 41% lower risk of mortality (adjusted hazard ratio [aHR], 0.59; 95% CI, 0.52-0.68; P < .001), and recipients from younger donors were at a 31% lower risk of mortality (aHR, 0.69; 95% CI, 0.66-0.71; P < .001) compared with respective donors from 2003 through 2009.

    All-Cause Graft Loss in Recipients of Liver Grafts From Older Donors

    Similar to the findings for mortality, graft loss among recipients of liver grafts from older and younger donors improved (Figure 3B and D). Quiz Ref IDAmong recipients of liver grafts from older donors from 2003 through 2009 to 2010 through 2016, 1-year graft loss improved from 23% to 15%, 3-year from 34% to 22%, and 5-year from 43% to 27%. Among recipients of liver grafts from younger donors, 1-year graft loss improved from 16% to 11%, 3-year from 26% to 19%, and 5-year from 32% to 24%. The improvements in graft loss were more marked in recipients of liver grafts from older donors (P = .03 for interaction) (Figure 3D). From 2010 through 2016, recipients of liver grafts from older donors were at a 40% lower risk of graft loss (aHR, 0.60; 95% CI, 0.53-0.68; P < .001), and recipients of live grafts from younger donors were at a 30% lower risk of graft loss (aHR, 0.70; 95% CI, 0.68-0.72; P < .001) compared with respective donors from 2003 through 2009.

    Discussion

    In this national study of 4127 recovered liver grafts from older donors and 3350 recipients of liver grafts from older donors between 2003 through 2016, we observed decreasing use of liver grafts from older donors with concomitant significant improvements in all-cause graft loss and mortality among recipients of these organs. Liver graft discard from older donors increased from 11.6% to 15.4% during the study period, and the proportion of transplants from older donors performed among all liver transplants decreased from 6.0% to 3.2% (P = .001). However, during the same period, all-cause graft loss and mortality decreased by more than half and improvements in all-cause graft loss and mortality among recipients of liver grafts from older donors were significantly higher than improvements seen among recipients of liver grafts from younger donors.

    Our findings from 2003 through 2016 of increased liver graft discard from older donors were consistent with findings from Orman et al22 of increased discard of all adult liver grafts from 2003 through 2010, along with worsening quality of grafts because of obesity and diabetes in the donor population and donation after cardiac death.27 Our findings of high liver graft discard from older donors and wide OPO-level variation of use of liver grafts from older donors were consistent with previous studies that examined variation in use of liver grafts from older donors and donation after cardiac death at the OPO level (0%-35.3% of adult donor liver transplants performed)15 and grafts from older donors used by United Network for Organ Sharing region (0.9%-12.9% of adult donor liver transplants performed).28 However, we expanded on these findings and showed that, after accounting for other donor characteristics, only 5.7% of the variation in graft discard from older donors was associated with OPO. Furthermore, we found that if all OPOs performed at least at the level of the national average for discard, 177 more grafts from older donors would have been available for liver transplant.

    Our findings of improved posttransplant mortality and all-cause graft loss may be associated with several factors, including patient care, surgical technique, or improved donor to recipient matching. We previously identified a recipient phenotype, a preferred recipient, who is likely to not incur additional risk associated with graft use from an older donor.29 Preferred recipients are first-time transplant recipients older than 45 years with a BMI less than 35, nonstatus 1 registration, cold ischemia time of less than 8 hours, and an indication for liver transplant other than hepatitis C virus. A study30 recently validated this preferred recipient phenotype and found that 28.4% of grafts from older donors were assigned to preferred recipients in 2006, but this increased to 59.1% in 2013, meaning that grafts from older donors were more frequently being transplanted in recipients who were likely to not incur additional risk of all-cause graft loss or mortality with liver grafts from older donors. These preferred recipients represent a potential group that could be used for broader use of grafts from older donors. Exclusion of a potential organ donor should not be based on age alone, but donor age should be evaluated with donor to recipient matching and consideration of potential cold ischemia time.

    Strengths and Limitations

    Strengths of this study included a large national cohort of liver grafts from older donors and recipients dating back to the implementation of the MELD allocation system. A notable limitation was the inability to determine whether the improvement in outcomes was associated with improved posttransplant care or improved older donor candidate selection.29,30 Judicious recipient selection to potentially increase use of older donor grafts is imperative; we do not advocate that every candidate receive a graft from an older donor. Although the overall improvement in outcomes for recipients of liver grafts from older donors is encouraging, further study is needed to determine the causes of this improvement. In addition, we cannot quantify the potential expansion of the donor pools with increased use of liver grafts from older donors because most potential older donors were not evaluated by the OPOs, and discard rates were likely to have been underestimated.

    Conclusions

    These findings revealed a continued decrease in the use of liver grafts from older donors despite improving outcomes for recipients. Although the results suggest that outcomes for all recipients have improved, there was a more marked improvement in outcomes of recipients of liver grafts from older donors. These trends may suggest that the transplant community has improved selection of who should receive grafts and enhanced care for recipients of liver grafts from older donors, and there may be room for more liberal and broader use of liver grafts from older donors to expand the donor pool. These findings may guide OPO evaluation of potential donors, transplant surgeon use of grafts from older donors, and patient clinical decision making.

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    Article Information

    Accepted for Publication: October 28, 2018.

    Corresponding Author: Dorry L. Segev, MD, PhD, Department of Surgery, Johns Hopkins University School of Medicine, 2000 E Monument St, Baltimore, MD 21205 (dorry@jhmi.edu).

    Published Online: February 13, 2019. doi:10.1001/jamasurg.2018.5568

    Author Contributions: Drs Haugen and Segev had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Haugen, Luo, Garonzik-Wang, Philosophe, McAdams-DeMarco, Segev.

    Acquisition, analysis, or interpretation of data: Haugen, Holscher, Luo, Bowring, Orandi, Thomas, Massie, McAdams-DeMarco, Segev.

    Drafting of the manuscript: Haugen, Holscher, Luo, Orandi, Thomas, McAdams-DeMarco, Segev.

    Critical revision of the manuscript for important intellectual content: Haugen, Holscher, Luo, Bowring, Orandi, Thomas, Garonzik-Wang, Massie, Philosophe, Segev.

    Statistical analysis: Haugen, Holscher, Luo, Bowring, Thomas, McAdams-DeMarco.

    Obtained funding: Haugen, McAdams-DeMarco.

    Administrative, technical, or material support: Haugen, Holscher, Bowring, Massie, Philosophe.

    Supervision: Orandi, Garonzik-Wang, Massie, Philosophe, Segev.

    Conflict of Interest Disclosures: Drs Holscher, Massie, and Segev reported grants from the National Institute of Diabetes and Digestive and Kidney Diseases, and Drs Haugen and McAdams-DeMarco reported grants from the National Institute on Aging during the conduct of the study. No other disclosures were reported.

    Funding/Support: Funding for this study was provided by grants F32AG053025 (Dr Haugen), F32DK109662 (Dr Holscher), K01AG043501 and R01AG055781 (Dr McAdams-DeMarco), and K24DK101828 (Dr Segev) from the National Institute of Diabetes and Digestive and Kidney Disease and the National Institute on Aging.

    Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

    Disclaimer: The interpretation and reporting of these data are the sole responsibility of the authors and should not be seen as an official policy of or interpretation by the Scientific Registry of Transplant Recipients, Organ Procurement and Transplantation Network, United Network for Organ Sharing, or the US government.

    Additional Information: Data have been supplied by the Minneapolis Medical Research Foundation as the contractor for the Scientific Registry of Transplant Recipients.

    References
    1.
    Israni  AK, Zaun  D, Rosendale  JD, Schaffhausen  C, Snyder  JJ, Kasiske  BL.  OPTN/SRTR 2016 annual data report: deceased organ donation.  Am J Transplant. 2018;18(suppl 1):434-463. doi:10.1111/ajt.14563PubMedGoogle ScholarCrossref
    2.
    Kim  WR, Lake  JR, Smith  JM,  et al.  OPTN/SRTR 2015 annual data report: liver.  Am J Transplant. 2017;17(suppl 1):174-251. doi:10.1111/ajt.14126PubMedGoogle ScholarCrossref
    3.
    Pondrom  S.  White House holds summit on organ transplantation.  Am J Transplant. 2016;16(8):2241-2242. doi:10.1111/ajt.13942PubMedGoogle ScholarCrossref
    4.
    Pruett  TL, Chandraker  A.  The White House Organ Summit: what it means for our field.  Am J Transplant. 2016;16(8):2245-2246. doi:10.1111/ajt.13947PubMedGoogle ScholarCrossref
    5.
    Alexander  JW, Vaughn  WK.  The use of “marginal” donors for organ transplantation. The influence of donor age on outcome.  Transplantation. 1991;51(1):135-141. doi:10.1097/00007890-199101000-00021PubMedGoogle ScholarCrossref
    6.
    Alexander  JW, Vaughn  WK, Carey  MA.  The use of marginal donors for organ transplantation: the older and younger donors.  Transplant Proc. 1991;23(1 pt 2):905-909.PubMedGoogle Scholar
    7.
    Busuttil  RW, Tanaka  K.  The utility of marginal donors in liver transplantation.  Liver Transpl. 2003;9(7):651-663. doi:10.1053/jlts.2003.50105PubMedGoogle ScholarCrossref
    8.
    Statistical Abstract of the United States: 2010. US Census Bureau 2012. https://www.census.gov/library/publications/2011/compendia/statab/131ed.html. Accessed August 1, 2018.
    9.
    Montenovo  MI, Hansen  RN, Dick  AA, Reyes J.  Donor age still matters in liver transplant: results From the United Network for Organ Sharing-Scientific Registry of Transplant Recipients database.  Exp Clin Transplant. 2017;15(5):536-541.PubMedGoogle Scholar
    10.
    Stewart  ZA, Locke  JE, Segev  DL,  et al.  Increased risk of graft loss from hepatic artery thrombosis after liver transplantation with older donors.  Liver Transpl. 2009;15(12):1688-1695. doi:10.1002/lt.21946PubMedGoogle ScholarCrossref
    11.
    Feng  S, Goodrich  NP, Bragg-Gresham  JL,  et al.  Characteristics associated with liver graft failure: the concept of a donor risk index.  Am J Transplant. 2006;6(4):783-790. doi:10.1111/j.1600-6143.2006.01242.xPubMedGoogle ScholarCrossref
    12.
    Reese  PP, Sonawane  SB, Thomasson  A, Yeh  H, Markmann  JF.  Donor age and cold ischemia interact to produce inferior 90-day liver allograft survival.  Transplantation. 2008;85(12):1737-1744. doi:10.1097/TP.0b013e3181722f75PubMedGoogle ScholarCrossref
    13.
    Sayuk  GS, Leet  TL, Schnitzler  MA, Hayashi  PH.  Nontransplantation of livers from deceased donors who are able to donate another solid organ: how often and why it happens.  Am J Transplant. 2007;7(1):151-160. doi:10.1111/j.1600-6143.2006.01600.xPubMedGoogle ScholarCrossref
    14.
    Paterno  F, Wima  K, Hoehn  RS,  et al.  Use of elderly allografts in liver transplantation.  Transplantation. 2016;100(1):153-158. doi:10.1097/TP.0000000000000806PubMedGoogle ScholarCrossref
    15.
    Croome  KP, Lee  DD, Keaveny  AP, Taner CB.  Noneligible donors as a strategy to decrease the organ shortage.  Am J Transplant. 2017;17(6):1649-1655. doi:10.1111/ajt.14163PubMedGoogle Scholar
    16.
    Barbier  L, Cesaretti  M, Dondero  F,  et al.  Liver transplantation with older donors: a comparison with younger donors in a context of organ shortage.  Transplantation. 2016;100(11):2410-2415. doi:10.1097/TP.0000000000001401PubMedGoogle ScholarCrossref
    17.
    Bertuzzo  VR, Cescon  M, Odaldi  F,  et al.  Actual risk of using very aged donors for unselected liver transplant candidates: a European single-center experience in the MELD era.  Ann Surg. 2017;265(2):388-396. doi:10.1097/SLA.0000000000001681PubMedGoogle ScholarCrossref
    18.
    Halazun  KJ, Quillin  RC, Rosenblatt  R,  et al.  Expanding the margins: high volume utilization of marginal liver grafts among >2000 liver transplants at a single institution.  Ann Surg. 2017;266(3):441-449. doi:10.1097/SLA.0000000000002383PubMedGoogle ScholarCrossref
    19.
    Ghinolfi  D, Marti  J, De Simone  P,  et al.  Use of octogenarian donors for liver transplantation: a survival analysis.  Am J Transplant. 2014;14(9):2062-2071. doi:10.1111/ajt.12843PubMedGoogle ScholarCrossref
    20.
    Su  F, Yu  L, Berry  K,  et al.  Aging of liver transplant registrants and recipients: trends and impact on waitlist outcomes, post-transplantation outcomes, and transplant-related survival benefit.  Gastroenterology. 2016;150(2):441-53.e6. doi:10.1053/j.gastro.2015.10.043PubMedGoogle ScholarCrossref
    21.
    United Network for Organ Sharing Reports. Deceased Donors Recovered in the United States by Donor Age, 2016. https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/#. Accessed August 1, 2018.
    22.
    Orman  ES, Barritt  AS  IV, Wheeler  SB, Hayashi  PH.  Declining liver utilization for transplantation in the United States and the impact of donation after cardiac death.  Liver Transpl. 2013;19(1):59-68. doi:10.1002/lt.23547PubMedGoogle ScholarCrossref
    23.
    Goldberg  D, Ditah  IC, Saeian  K,  et al.  Changes in the prevalence of hepatitis C virus infection, nonalcoholic steatohepatitis, and alcoholic liver disease among patients with cirrhosis or liver failure on the waitlist for liver transplantation.  Gastroenterology. 2017;152(5):1090-1099.e1. doi:10.1053/j.gastro.2017.01.003PubMedGoogle ScholarCrossref
    24.
    Organ Procurement and Transplantation Network. https://optn.transplant.hrsa.gov/media/1200/optn_policies.pdf#nameddest=Policy_09. Accessed January 4, 2019.
    25.
    Massie  AB, Kucirka  LM, Segev  DL.  Big data in organ transplantation: registries and administrative claims  [published correction appears in Am J Transplant. 2014;14(11):2673].  Am J Transplant. 2014;14(8):1723-1730. doi:10.1111/ajt.12777PubMedGoogle ScholarCrossref
    26.
    Louis  TA, Zeger  SL.  Effective communication of standard errors and confidence intervals.  Biostatistics. 2009;10(1):1-2. doi:10.1093/biostatistics/kxn014PubMedGoogle ScholarCrossref
    27.
    Orman  ES, Mayorga  ME, Wheeler  SB,  et al.  Declining liver graft quality threatens the future of liver transplantation in the United States.  Liver Transpl. 2015;21(8):1040-1050. doi:10.1002/lt.24160PubMedGoogle ScholarCrossref
    28.
    Halazun  KJ, Rana  AA, Fortune  B,  et al.  No country for old livers? examining and optimizing the utilization of elderly liver grafts.  Am J Transplant. 2018;18(3):669-678. doi:10.1111/ajt.14518PubMedGoogle Scholar
    29.
    Segev  DL, Maley  WR, Simpkins  CE,  et al.  Minimizing risk associated with elderly liver donors by matching to preferred recipients.  Hepatology. 2007;46(6):1907-1918. doi:10.1002/hep.21888PubMedGoogle ScholarCrossref
    30.
    Haugen  CE, Thomas  AG, Garonzik-Wang  J, Massie  AB, Segev  DL.  Minimizing risk associated with older liver donors by matching to preferred recipients: a national registry and validation study.  Transplantation. 2018;102(9):1514-1519. doi:10.1097/TP.0000000000002190PubMedGoogle ScholarCrossref
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