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. Author manuscript; available in PMC: 2017 Jun 7.
Published in final edited form as: Exp Clin Transplant. 2016 Oct;14(5):463–470.

Donations After Circulatory Death in Liver Transplant

Emre A Eren 1,4, Nicholas Latchana 1, Eliza Beal 1,4, Don Hayes Jr 2,5, Bryan Whitson 3,4, Sylvester M Black 1,4
PMCID: PMC5461820  NIHMSID: NIHMS863290  PMID: 27733105

Abstract

The supply of liver grafts for treatment of end-stage liver disease continues to fall short of ongoing demands. Currently, most liver transplants originate from donations after brain death. Enhanced utilization of the present resources is prudent to address the needs of the population. Donation after circulatory or cardiac death is a mechanism whereby the availability of organs can be expanded. Donations after circulatory death pose unique challenges given their exposure to warm ischemia. Technical principles of donations after circulatory death procurement and pertinent studies investigating patient outcomes, graft outcomes, and complications are highlighted in this review. We also review associated risk factors to suggest potential avenues to achieve improved outcomes and reduced complications. Future considerations and alternative techniques of organ preservation are discussed, which may suggest novel strategies to enhance preservation and donor expansion through the use of marginal donors. Ultimately, without effective measures to bolster organ supply, donations after circulatory death should remain a consideration; however, an understanding of inherent risks and limitations is necessary.

Keywords: Donor selection, Tissue and organ procurement

Introduction

Liver transplant remains the only cure for end-stage liver disease.1 Historically, organs were obtained for transplant after cardiac arrest of donors until 1968, when the Committee of Harvard Medical School promoted the acceptance of brain death.2 With this recognition, organ donation after brain death (DBD) became widespread among transplant centers, with DBD accounting for 92.1% of transplants.3 Unfortunately, the present volume of transplants is insufficient to meet the demands. In the United States, 15027 individuals were registered on the liver transplant wait list in 2013, while only 5921 hepatic grafts were transplanted.4 Given this discrepancy, the use of organs after circulatory arrest (cardiac death) of donors (DCD) that fail to meet the full criteria of brain death or deemed neurologically intact have grown in acceptance.5 Donations after circulatory death account for 12.1% of total transplants, which is up from 1.9% in 2000.3 However, there is potentially room to further expand its use, given that 10.5% of potentially suitable DCDs are discarded.3

Donations after circulatory death are classified into 5 categories depending on the circumstances of death (Table 1).6,7 Donations after circulatory death differ from DBDs based on the length of warm ischemic time (WIT), which represents the time between cardiac death and organ cooling during procurement. Unlike DCDs, DBDs do not usually have WIT before procurement. Notably, controlled DCDs have WIT that can be estimated, resulting in reduced ischemic insult relative to uncontrolled donors, where the WIT is often inexact and extended, making assessment of injury difficult.

Table 1.

Categories of Donors After Cardiac Death6,7

Category Description of Donor Uncontrolled or Controlled Warm Ischemia
Category 1 Brought in dead Uncontrolled
Category 2 Unsuccessful resuscitation Uncontrolled
Category 3 Awaiting cardiac arrest Controlled
Category 4 Cardiac arrest after brain death Controlled
Category 5 Cardiac death in hospital as inpatient Uncontrolled
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The outcome of DCD transplants is organ dependent. Renal transplants performed from uncontrolled DCDs have equivalent outcomes compared with controlled DCDs.8 Furthermore, renal grafts with uncontrolled DCDs were found to have comparable results to DBDs, suggesting renal tolerance of ischemia.9 Conversely, liver grafts are more susceptible to ischemia, which can lead to unfavorable outcomes.10 As a result, category 3 donors are most often used for liver transplants to ensure a controlled environment where WIT can be closely monitored. In addition, the percentage of unused livers from DCDs has risen consistently for several years.11 Given the underuse of DCDs for transplants and the continued demand for obtaining suitable organs, we highlight the current procedures and pertinent literature related to DCD outcomes, complications, risk factors, and future considerations, including novel methods of hepatic organ preservation.

Procedure of donations after circulatory death

Rapid recovery techniques are used for DCD procurement, and these may also involve premortem cannulation.12,13 Commencement of the procedure involves withdrawal of ventilator and perfusion support, during which the patient is monitored until the end of cardiorespiratory function. Administration of heparin at the time of withdrawal has met resistance, given the potential for hastened death; however, its use is still considered standard practice.14 On declaration of death, 5 minutes should elapse to ensure the absence of autoresuscitation.15

Donations after circulatory death for liver transplant can be separated into 3 main phases based on organ temperature. The first phase represents WIT after withdrawal of cardiopulmonary support and lasts until cold flush of the organ.15 This phase includes organ procurement. To minimize WIT, premortem cannulation can be performed through access of the femoral artery and vein before withdrawal of support.12 If premortem cannulation is not performed, aortic and portal system cannulation is completed after declaration of death. After explantation, the liver is flushed with cold preservation solution, thus ending WIT and commencement of the second phase, cold ischemic time (CIT). Cold ischemic time lasts until the organ is successfully transplanted in the recipient, which is largely governed by transportation time of organs. Last, another WIT period ensues after reperfusion of the organ.

Outcomes

Several database analyses have shown inferior patient and graft survival for DCD liver transplants.16–19 An analysis by Abt and associates revealed DCD liver transplants had 1- and 3-year graft survival rates of 70.2% and 63.3% compared with DBD grafts, which were 80.4% and 72.1% (P = .003 and P = .012).16 Similarly Mateo and associates found reduced graft survival for DCD compared with DBD (1- and 3-year graft survival rates for DCD of 71% and 60% vs DBD having 80% and 72%; P < .001).17 The disparity between DCD and DBD liver grafts is further supported by 2 Scientific Registry of Transplant Recipients analyses. The first study by Merion and associates showed an 85% higher risk of graft failure for DCD over DBD, with 3-month, 1-year, and 2-year survival rates of 83.0%, 70.1%, and 60.5% versus 89.2%, 83.0%, and 75.0% (P < .001).18 Selck and associates found similar trends, with 6-month, 1-year, 2-year, and 3-year graft survivals of 79%, 72%, 63%, and 57% versus 88%, 84%, 78%, and 74% for DCD and DBD (P < .001).19 The higher graft failure associated with DCD was suggested to occur within the first 180 days.19

Akin to graft survival, several single-center studies (Table 2) have suggested reduced patient survival associated with DCD liver transplants relative to DBD.20–22 Foley and associates reported reduced patient survival at 1 and 3 years (80% and 68% with DCD vs 91% and 84% with DBD; P = .002) and diminished graft survival at 1 and 3 years (67% and 56% with DCD vs 86% and 80% with DBD; P = .0001) associated with DCD donors.20 In contrast, Skaro and associates found no significant difference in patient survival, although lower 1- and 3-year graft survival rates in DCD relative to DBD were found (61.3% and 52.6% with DCD vs 85.2% and 74.2% with DBD; P = .005).21 Furthermore, there was a 3.2-fold higher risk of retransplant among DCD livers compared with DBD.21 Similarly, de Vera and associates did not find a significant difference in patient survival; however, 1-, 5-, and 10-year graft survival rates were significantly worse for DCD compared with DBD transplants (69%, 56%, and 57% vs 82%, 73%, and 63%; P < .0001).22 Furthermore, other evidence suggests a potential link between DCD liver transplants and acute kidney injury in patients with no history of renal damage.23

Table 2.

Single-Center Outcomes of Donations After Circulatory Death Versus Donations After Brain Death

Study Year DCD or DBD (No. of Patients) % Patient Survival at 1, 3, and 5 years % Graft Survival at 1, 3, and 5 years Donor Age, y Recipient Age, y Mean WIT, min Mean CIT, min Mean MELD
D’Alessandro et al.69 2000 DCD (19) -, 72.6, - -, 53.8, - 32.0 ± 15.1 47.4 ± 18.5 16.4 ± 10.9 474 ± 138
DBD (364) -, 84.8, - -, 80.9, - 32.8 ± 15.9 47.7 ± 14.3 504 ± 150
Abt et al.70 2003 DCD (n=15) 79.0, 79.0, - 71.8, 71.8, - 30.1 ± 10.4 20.4 ± 6 366.4 ± 131
DBD (n=221) 90.9, 77.7, - 85.4, 73.9, - 38.4 ± 17.4 464.0 ± 149
Manzarbeitia et al.71 2004 DCD (n=19) 89.5, 83.5 (2 year), - 33.95 ± 17.93 19.67 ± 7.68 574 ± 84
DBD (n=311) 84.2, 82.0 (2 year), -
Muiesan et al.72 2005 DCD (n=32) 89.6, -, - 86.5, -, - 36 ± 14.9 38.4 (0.7–72) 14 ± 5.3 516 (312–858)
DBD (n=0)
Fujita et al.28 2007 DCD (n=24) 86.8, 81.7, - 69.1, 58.6, - 31.6 51.1 12.8 ± 7.4 482 22.1
DBD (n=1209) 84.0, 76.0, - 78.7, 70.2, - 35.1 42 497 23.6
Detry et al.31 2009 DCD (n=13) 100, 78.5 (2yr), - 100, 78.5 (2 y), - 51 (25–71) 55 (50–70) <30 295 14.2 (8–25)
DBD (n=0)
Grewal et al.27 2009 DCD (n=108) 91.5, 88.1, 88.1 79.3, 74.5, 71.0 41 ± 17 55 ± 11 22.3 378 ± 102 17 ± 7.9
DBD (n=1328) 87.3, 81.1, 77.2 81.6. 74.7. 69.1 48 ± 20 55 ± 10 429 ± 126 18 ± 8.6
Pine et al.73 2009 DCD (n=39) 82.1, 100, - 79.5, 63.6, - 41.85 (12–68) 50.59 (18–67) 352.21 (161–606) 14.23 (6–26)
DBD (n=39) 68.2, 100, - 97.4, 97.4, - 42.87 (19–69) 49.38 (22–66) 593.87 (130–956) 15.23 (6–32)
Skaro et al.21 2009 DCD (n=32) 74.0, 74.0,- 61.3, 52.6, - 43.1 ± 17.6 53.1 ± 12.8 15.1 ± 4.6 330 ± 90 22.9 ± 10.2
DBD (n=237) 90.4, 80.7, - 85.2, 74.2, - 44.7 ± 17.6 54.9 ± 10.0 312 ± 90 21.9 ± 10.1
de Vera et al.22 2009 DCD (n=141) 79, -, 70, 57 (10yr) 69, - 56, 44 (10y) 37.1 ± 15.9 53.1 ± 10.7 19.8 ± 8.8 657 ± 170 18.3 ± 9
DBD (n=282) 85, -, 76, 64 (10yr) 82, -, 73, 63 (10 y) 39.1 ± 16.1 53.7 ± 9.3 636 ± 177 18.5 ± 9
Bartlett et al.30 *pediatric 2010 DCD (n=14) 100, -, - 100, -, - 23 ± 10.64 7 (8 mo-16 y) 16 (11–29) 420 (330–504) -
DBD (n=0)
Foley et al.32 2011 DCD (n=87) 84, -, 68, 54 (10yr) 69, -, 56, 43 (10 y) 35.8 ± 13.3 50.5 ± 13.1 20.8 ± 9.4 432 ± 138 19.7 ± 8.9
DBD (n=1157) 91, -, 81, 67 (10yr) 86, -, 76, 60 (10 y) 36.5 ± 13.3 47.5 ± 16.7 498 ± 138 20.1 ± 8.7
Hong et al.43 2011 DCD (n=81) 78, 62, 53 36 ± 10 54 ± 11 26 ± 9 375 ± 138 24 ± 10
DBD (n=0)
Croome et al.26 2012 DCD (n=36) 91, 80 (2yr) 91, 73 (2 y) 41.8 ±13.19 53.6 ± 8 35 ± 18 336 ± 66 17.5 ± 8.3
DBD (n=327) 45.93 ± 10.04 54.95 ± 10.07 432 ± 150 18.98 ± 9.79
Leithead et al.23 2012 DCD (n=88) 84.9, 78.0, - 83.7, 77.0, - 46.4 ± 16.1 55.7 ± 8.5 20.1 ± 9.0 448 ± 114 14 ± 5
DBD (n=88) 90.5, 83.4, - 88.2, 81.3, - 50.4 ± 14.6 56.0 ± 9.2 498 ± 144 13 ± 4
Meurisse et al.25 2012 DCD (n=30) 93, 85, 85 90, 82, 82 51 (37–59) 60 (52–65) 24 (18–30) 414 (325–471) 15 (11–17)
DBD (n=385) 88, 78, 72 85, 74, 68 53 (42–64) 58 (49–64) 516 (433–606) 16 (11–23)
Taner et al.37 2012 DCD (n=200) 92.6, 85.0, 80.9 80.9, 72.7, 68.9 40.3 ± 16.4 55.1 ± 9.4 25.3 ± 10.8 360 ± 90 17.9 ± 7.9
DBD (n=1828) 89.8, 83.0, 76.6 83.3, 75.1, 68.6 46.6 ± 19.7 54.1 ± 10.4 420 ± 114 18.5 ± 8.6
Vanatta et al.29 2013 DCD (n=38) 92, 80, - 92, 74, - 33 ± 15 56 ± 8 21 ± 8 289 ± 97 16 ± 3
DBD (n=76) 92, 86, - 91, 85, - 34 ± 15 55 ± 7 280 ± 11 18 ± 6
Doyle et al.74 2015 DCD (n=49) 95.9, 90.6, 87.1 93.6, 86.0, 79.5 29.1 ± 12.8 56.4 ± 10.4 33.6 ± 9.3 342 ± 114 18.7 ± 7.1
DBD (n=98) 94.7, 83.5, 80.3 92.6, 81.4, 78.1 29.9 ± 12.1 54.9 ± 65.3 342 ± 132 18.3 ± 7.3
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Abbreviations: CIT, cold ischemic time; DBD, donations after brain death; DCD, donation after circulatory (cardiac) death; MELD, model for end-stage liver disease; WIT, warm ischemic time

In contrast, a review of the United Network for Organ Sharing database found the use of DCD livers in pediatric patients to be comparable with DBD, with 1- and 3-year graft survival rates of 89.2% and 79.3% for DCD versus 75.6% and 65.8% for DBD (P = .3).24 Additionally, many single-center studies (Table 2) have suggested that both graft function and patient survival are comparable between DCD and DBD liver transplants.25–29 Meurisse and associates reported DCD liver transplants had 1, 3, and 5-year graft survival rates of 90%, 82%, and 82% and patient survival rates of 93%, 85%, and 85%, which were similar to DBD liver transplant survival rates of 85%, 74%, and 68% (P = .524) and patient survival rates of 88%, 78%, and 72% (P = .348).25 Grewal and associates were able to achieve comparable long-term outcomes between DCD and DBD liver transplants with 1-, 3-, and 5-year patient and graft survival rates for DCD transplants (91.5%, 88.1%, and 88.1% and 79.3%, 74.5%, and 71.0%) vs DBD transplants (87.3%, 81.1%, and 77.2% and 81.6%, 74.7%, and 69.1%).27 These findings are supported by Fujita and associates and Vanatta and associates.28,29 Other studies suggest that the patient and graft survival rates after 1 year with DCD liver transplants are 100%; however, these studies contain small sample sizes and no comparisons to DBD.30,31

Risk factors and complications

Donor and recipient risk factors leading to complications after DCD liver transplants have been identified (Table 3). Donor age > 50 years, WIT > 30 minutes, and CIT > 8 hours are documented risk factors for graft failure.16,19,20,32,33 Donor weight > 200 kg has been reported as well.34,35 Notably, Lee and associates found a significantly increased risk of graft loss when WIT was > 15 minutes.33 Importantly, true warm ischemia (time from significant hypotension to cold flush) has been used interchangeably with total WIT (period from extubation to cold flush), which may lead to inaccuracies in the interpretation of studies.14 A recommendation for the division of WIT into 2 distinct phases has been proposed, with phase 1 including the period from withdrawal of support to cardiopulmonary cessation and phase 2 including the time from loss of circulation to cold flush.14 Halazun and associates36 also stressed the need for distinction between warm ischemia during organ procurement and warm ischemia after reperfusion. Furthermore, Taner and associates suggested a link between the duration of asystole-to-cross clamping and the development of ischemic cholangiopathy (P < .05).37 A CIT of < 8 hours is preferred for DCD liver transplants, as Chan and associates35 and Foley and associates32 have revealed an increased risk of ischemic cholangiopathy with prolonged CIT (P = .05). To minimize CIT, some institutions start explantation of the recipient once the donor is deemed suitable.32 Detry and associates noted that a short WIT of < 30 minutes and CIT of < 5 hours resulted in 100% patient and graft survival at 1 year.31

Table 3.

Possible Risk Factors with Liver Transplant With Donations After Circulatory Death

Donor age15,16,21,22,32,34,35,43,49,75
Donor weight > 100 kg34,35
Recipient age > 60 years34,75
> 30 kg/m2 Recipient body-mass index 22,43
Recipient Black race34,37
Warm ischemic time > 30 minutes20,22,32,34,43,70
Asystole to cross-clamp duration37
Cold ischemic time > 8 hours16,21,22,25,32,34,43
Hepatocellular carcinoma42,75
MELD Score17,21,22,34,49
Hepatitis C34,40,41,75
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Abbreviations: DBD, donations after brain death; DCD, donation after circulatory (cardiac) death; MELD, model for end-stage liver disease

Several recipient characteristics can increase the risk of poor DCD outcomes, including high Model for End-stage Liver Disease scores, which have been associated with graft failure and biliary complications in some studies, whereas other studies refute this claim.26,38,39 In addition, hepatitis C virus-positive recipients may be at increased risk for hepatitis C virus recurrence.40,41 Recently, Croome and associates found that transplant recipients with hepatocellular carcinoma may have inferior survival rates after DCD transplant (P = .049).42 Black recipient race and recipient body mass index > 30 kg/m2 have also been indicated as adverse outcomes with DCDs.22,34,37,43

There are various complications associated with DCD liver transplants (Table 4). Primary nonfunction, delayed graft function, and hepatic artery thrombosis have been associated with DCD livers, and these complications may contribute to higher rates of retransplant. Biliary complications have also been suggested to occur with increased frequency in DCDs.20,25,26,44 A single-center study showed an overall biliary complication rate of 50% for DCDs versus 28.3% for DBDs (P = .012) with biliary stricture rates of 46.7% and 26.5% (P = .018).25 Croome and associates reported that 25% of DCD liver transplants developed biliary complications compared with 13% of DBD liver transplants (P = .062).26 These trends are supported by Foley and associates and Chan and associates.32,35 Therefore, routine use of T-tube insertion in DCD transplants has been suggested for biliary drainage and early detection of leaks.15 However, to date, there are inconclusive data to support routine use of T-tubes in DCD transplant procedures.45

Table 4.

Single-Center Complications for Donations after Circulatory Death Versus Donations after Brain Death

Study Complication DCD DBD P Value
D’Alessandro et al.69
General biliary
Ischemic cholangiopathy 5.3 4.6
Hepatic artery thrombosis 0 3.8
Hepatic artery stenosis 10.5 5.2
Portal vein thrombosis 0 3.8
Primary nonfunction 10.5 1.3 .04
Retransplantation 21.1
Abt et al.70
General biliary 33.3 9.5 < .01
Ischemic cholangiopathy 20 2.3 < .01
Anastomotic biliary strictures 6.7 5.4
Vascular
Hepatic artery thrombosis 0 3.2 > .05
Portal vein thrombosis 0 0.4
Primary nonfunction 6.7 3.6 > .05
Manzarbeitia et al.71
General biliary 10.5 13.8 .68
Retransplantation 10.5 8.7 .68
Muiesan et al.72
General biliary 9.4
Anastomotic biliary strictures 6.3
Hepatic artery thrombosis 6.3
Retransplantation 3.1
Fujita et al.28
General biliary 25 21
Ischemic cholangiopathy 12.5 9.1 .568
Hepatic artery thrombosis 8.3 4.1 .312
Portal vein thrombosis 4.2 2.6 .648
Primary nonfunction 0 2.8 .405
Retransplantation 20.8 9.4 .059
Chan et al.35
General biliary
Ischemic cholangiopathy 13.7 1 .001
Anastomotic biliary strictures 9.8 78 NS
Hepatic artery thrombosis 0 4.8 NS
Primary nonfunction 0 3.2 NS
Detry et al.31
General biliary 15
Anastomotic biliary strictures 7.7
Primary nonfunction 0
Retransplantation 0
Grewal et al.27
General biliary
Ischemic cholangiopathy 8.3 1.9 .008
Hepatic artery thrombosis 0.9 1.7 .469
Primary nonfunction 3.7 1.4 .09
Retransplantation 14.8 9.3 .107
Recurrent hepatitis C 3.7 3.1 .449
Pine et al.73
General biliary 33.3 10.2
Ischemic cholangiopathy 20.5 0 .005
Anastomotic biliary strictures 10.2 10.2 1
Hepatic artery thrombosis 2.6 5.1 1
Hepatic artery stenosis 12.8 0 .27
Primary nonfunction 5.1 0 .494
Skaro et al.21
General biliary 53.1 21.5 < .001
Ischemic cholangiopathy 37.5 1.7 < .001
Hepatic artery thrombosis 9.4 3 .1
Primary nonfunction 3.1 0.4 .22
Retransplantation 21.9 6.8 .01
de Vera et al.22
General biliary 25 13 < .001
Ischemic cholangiopathy 16.3
Hepatic artery thrombosis 6 6 1
Primary nonfunction 12 3 < .001
Retransplantation 18 7 < .001
Foley et al.32
General biliary 47 26 < .01
Ischemic cholangiopathy 34 1 < .01
Anastomotic biliary strictures 14 11 .37
Hepatic artery thrombosis 8.5 2.9 .38
Hepatic artery stenosis 5.7 10.5 .18
Portal vein thrombosis 4 5 .54
Primary nonfunction 1.2 2.3 .31
Retransplantation 19 4.8 .0001
Hong et al.43
General biliary 29
Ischemic cholangiopathy 9.9
Croome et al.26
General biliary 25 13 .062
Ischemic cholangiopathy 5.6 0 < .001
Anastomotic biliary strictures 2.7 4 .7232
Leithead et al.23
Acute kidney injury 53.4 31.8 .035
Meurisse et al.25
General biliary 50 28.3 .012
Ischemic cholangiopathy 33.3 12.5 .001
Anastomotic biliary strictures 26.7 18.7 .287
Primary nonfunction 0 0
Retransplantation 0 2.8 .175
Taner et al.37
General biliary 36.7
Ischemic cholangiopathy 12.6
Hepatic artery thrombosis 3.3
Hepatic artery stenosis 5.1
Primary nonfunction 2.3
Retransplantation 13.9
Vanatta et al.29
General biliary 18.8 9.2 .225
Ischemic cholangiopathy 7.9 1.3 .107
Anastomotic biliary strictures 18.4 9.2 .225
Hepatic artery thrombosis 0 3.9 .55
Hepatic artery stenosis 10.5 6.6 .478
Portal vein thrombosis 0 5.3 .299
Primary nonfunction 2.6 1.3 1
Doyle et al.74
General biliary 34.6 22.4
Ischemic cholangiopathy 8.5 0
Anastomotic biliary strictures 16.3 12.2 .49
Hepatic artery thrombosis 0 0
Portal vein thrombosis 0 0
Primary nonfunction 0 0
Acute kidney injury 16.3 4.1 .01
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Abbreviations: DBD, donations after brain death; DCD, donation after circulatory (cardiac) death; NS, not significant

Of the possible biliary complications, ischemic cholangiopathy, also referred to as ischemic-type biliary strictures, is more prevalent in DCD transplants than in DBDs.32 Ischemic-type biliary stricture is regarded as the most severe biliary complication, as it can lead to intrahepatic bile duct strictures, hepatic abscesses, and hepatic necrosis, resulting in retransplant.34,37 Extended CIT and donor age correlate with an increased incidence of ischemic-type biliary strictures, whereas ischemia reperfusion injury can exacerbate these problems.32,35,46

Transplant procedures using DCD organs result in greater overall financial costs. The 1-year cost after liver transplant has been calculated at 82 730 Euros for DBD versus 101 805 Euros for DCD (P = .001).47 Not surprisingly, this analysis revealed increased complications associated with DCD grafts. It is important to note that patient and graft survival rates were not different between DCD and DBD grafts in the aforementioned study. Similarly, Jay and associates48 found increased 1-year posttransplant costs for DCD recipients (125% of DBD cost). The cost remained higher in DCD (120% of DBD) transplants despite the exclusion of retransplants, which is a major risk for DCD livers but occurs infrequently.48

In light of increased complications associated with DCD liver transplants, the optimal recipient of these grafts remains unclear. High-risk recipients are subjected to unnecessary risk when exposed to a DCD liver transplant, and low-risk recipients may be able to physically withstand possible complications resulting from DCD liver transplants.19 Vanatta and associates achieved comparable graft and patient survival rates between DCD and DBD liver transplants in recipients having low Model for End-stage Liver Disease scores (P = .444 and P = .295).29 Donors were young with total WIT < 30 minutes and CIT of approximately 5 hours.29 Conversely, the increased risk of DCD transplants may pose a favorable risk-to-benefit ratio only for high-risk recipients.49 Although the exact indication for DCD transplant remains unclear, attempts to minimize complications through focus on risk factor mitigation is a wise strategy.

Future considerations

Several methods to minimize the detrimental outcomes of DCD transplants have been proposed. Hypothermic machine perfusion has resulted in superior graft survival and reduced delayed graft function relative to static cold storage (SCS) in DCD renal grafts.50 For hepatic grafts, SCS involves vascular flush with cold preservation solution, followed by placement into cold slush to minimize metabolism.51,52 Hypothermic machine perfusion consists of constant perfusion of preservation solution administered via the hepatic artery and portal vein. Guarrera and associates have successfully used hypothermic machine perfusion in clinical trials with extended criteria donors, including DCDs, and have shown reduced biliary complications compared with SCS.53 Dutkowski and associates recently demonstrated comparable clinical results between unperfused DBD livers and DCD livers after hypothermic machine perfusion.54 Similarly, Dries and associates used a DCD porcine liver model to show reduced arteriolonecrosis of the peribiliary vascular plexus with hypothermic machine perfusion compared with SCS (P = .024).55 Experimental rat models have revealed that hypothermic oxygenated perfusion can protect from biliary injury after a period of warm ischemia.56 In addition, Lee and associates57 have demonstrated that rat livers undergoing hypot hermic machine perfusion for 5 hours can tolerate warm ischemia for 30 minutes, unlike models preserved with cold preservation solution alone.

Normothermic machine perfusion involves administration of warmed (37°C) preservation solution and provides an optimal metabolic environment, allowing for preservation, monitoring, and resuscitation of marginal organs.58,59 In a porcine model, after 1 hour of warm ischemia and 24 hours of cold storage, viability of livers could be achieved with normothermic machine perfusion, whereas livers preserved with SCS alone were not viable (P < .05).58 These results are supported by Xu and associates59 and Schon and associates.60 Normothermic machine perfusion was also shown to reduce liver and bile duct injury in a porcine DCD liver model.61 Recovery of DCD livers and successful transplant after an extended WIT has also been recorded in rat models.62 Rat livers subjected to 45 minutes of warm ischemia and 2 hours of cold storage were successfully recovered using normothermic machine perfusion and transplanted.63 Rat survival was 100% after 4 weeks, whereas rats receiving SCS livers died within 12 hours.63

Subnormothermic machine perfusion is an intermediate strategy, which entails graft cooling to 21°C, thereby permitting ongoing assessment of graft function and viability while minimizing metabolic demands.64 Dries and associates65 have demonstrated the feasibility of using subnormothermic machine perfusion to assess and preserve livers. A porcine DCD liver model showed reduced bile duct injury with use of subnormothermic machine perfusion.66 Likewise, several other groups have suggested that subnormothermic machine perfusion can recover and allow transplant of ischemic livers with promising results.64,67 Notably, successful preservation of rat livers for up to 4 days can be achieved using supercooling and subsequent subnormothermic machine perfusion.68 This method has the potential to prolong transport of DCD livers by 3- to 4-fold.68

Conclusions

Increasing the supply of hepatic grafts to meet the demands of those with end-stage liver disease remains a formidable challenge. Continued expansion of DCD graft utilization represents a potential avenue to help satisfy organ demands. Outcomes of DCD liver transplants have improved over time, with evidence to support noninferiority of DCD to DBD with respect to patient and graft outcomes. These outcomes are attributed, in part, to meticulous adherence to strict protocols and sound surgical techniques. Donations after circulatory death are subject to several complications, including biliary complications, primary nonfunction, and delayed graft function. As such, mitigating donor and recipient risk factors such as advanced donor age, WIT, and CIT are of prime importance. Ongoing investigations into improved preservation techniques and organ repair should continue and may ultimately negate the risk of using DCD livers. In the interim, the use of DCD livers remains a viable mechanism to expand the current donor pool; however, its use will need to be tempered against inherent shortcomings.

Acknowledgments

The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare.

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