The impact of ischemic cholangiopathy in liver transplantation using donors after cardiac death: The untold story

doi:10.1016/j.surg.2009.06.052

Surgery

Volume 146, Issue 4, October 2009, Pages 543-553

https://doi.org/10.1016/j.surg.2009.06.052 Get rights and content

Background

Liver transplantation (LT) from donation after cardiac death (DCD) donors is increasingly being used to address organ shortages. Despite encouraging reports, standard survival metrics have overestimated the effectiveness of DCD livers. We examined the mode, kinetics, and predictors of organ failure and resource utilization to more fully characterize outcomes after DCD LT.

Methods

We reviewed the outcomes for 32 DCD and 237 donation after brain death (DBD) LT recipients at our institution.

Results

Recipients of DCD livers had a 2.1 times greater risk of graft failure, a 2.5 times greater risk of relisting, and a 3.2 times greater risk of retransplantation compared with DBD recipients. DCD recipients had a 31.6% higher incidence of biliary complications and a 35.8% higher incidence of ischemic cholangiopathy. Ischemic cholangiography was primarily implicated in the higher risk of graft failure observed after DCD LT. DCD recipients with ischemic cholangiography experienced more frequent rehospitalizations, longer hospital stays, and required more invasive biliary procedures.

Conclusion

Related to higher complication rates, DCD recipients necessitated greater resource utilization. This more granular data should be considered in the decision to promote DCD LT. Modification of liver allocation policy is necessary to address those disadvantaged by a failing DCD graft.

Section snippets

Patients and methods

After receiving institutional review board approval, we performed a retrospective review of LT performed at Northwestern Memorial Hospital between December 2003 and May 2008. Adult (≥18 years) deceased donor (DCD and DBD) LT recipients were included in the analysis. Living donors, split liver recipients, multiorgan transplantations, and patients not undergoing primary transplant were excluded. Donor and recipient parameters were collected for comparison. Primary outcome measures included

Donor and recipient characteristics

From December 2003 to May 2008, 32 DCD and 237 DBD LT were performed at our center. There were no differences in donor age, gender, race, or body mass index between DCD and DBD donors (Table I). The average donor age was 43 ± 18 years for DCD and 45 ± 18 years for DBD donors (P = .63). Donor cause of death was different between the DCD and DBD groups (P < .006). In particular, DCD donors less often had cerebrovascular accident (DCD 25% vs DBD 42%) and more frequently had “other” (DCD 22% vs DBD

Discussion

National initiatives aimed at augmenting organ donation rates in the United States have succeeded in increasing both the number of donors as well as the number of organs transplanted per donor, but increases in standard criteria donors seem to have plateaued.² There remains a substantial imbalance between liver supply and demand for transplantation. In 2003, our OPO began heavily promoting DCD donors, and subsequently more DCD livers became available. We observed an increase in DCD livers in

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Should advanced perfusion be the standard of care for donation after circulatory death liver transplant?
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As an alternative to static cold storage (SCS), advanced perfusion techniques such as normothermic regional perfusion and ex-situ perfusion (normothermic or hypothermic) have emerged as a way to improve the ischemic injury suffered by donation after circulatory death (DCD) livers. Multiple studies have been published that have demonstrated superior post-DCD liver transplant outcomes when using advanced perfusion compared with SCS. In particular, these studies have shown lower rates of ischemic cholangiopathy with advanced perfusion. In addition to the improved post-liver transplant outcomes, studies have also demonstrated higher rates of liver utilization from DCD donors when advanced perfusion is used compared with SCS. Given the high rates of graft loss in patients who develop ischemic cholangiopathy, the significant reduction seen in DCD donor livers that have undergone advanced perfusion represents a key step in more broad utilization of these livers. With such compelling evidence from multiple trials, it seems reasonable to ask the question: should advanced perfusion be the standard of care for DCD liver transplant?
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After advancement of technical aspects, use of well-established and novel immunosuppressive therapies, and better pre and postoperative care, which resulted in high overall survival rates with liver transplantation, waiting list mortality has become the main issue for pediatric patients with end stage liver disease. Insufficient organ donors have become a challenging issue especially in the pediatric patient population, for whom size match of donor or graft is harder to achieve. In order to expand the donor pool and decrease the gap between the demand and supply of donor organs, use of donation after circulatory death (DCD) donors have been proportionally increased. In this chapter we aim to discuss current practices, issues and outcomes with DCD in pediatric liver transplantation, as well as future strategies for improvement of results.
Contemporary considerations in solid organ transplantation utilizing DCD donors
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Donation after cardiac death (DCD) has been leading the way to help bridge the growing gap between availability of donors and recipients on waitlist. With advances in technology and our understanding of DCD donation the safety profile is growing. It is becoming an increasing viable option even in marginal settings.
The ethos surroundings DCD is still a matter of contention but there is support and collaboration from larger societies and establishments with development of standardizing protocols. Preparation is key. Experience of the procurement and transplanting surgeons are pivotal. There are multiple moving parts and for the success of a DCD program, dedication is needed from the donor hospitals, organ procurement organizations and the transplant centers. Previous practices based on anecdotal experiences are now either supported by or refuted by increasing evidence and data, based on the development of consensus-based guidelines with the end goal of having uniform outcomes. Normothermic regional and machine perfusion have expanded options in the DCD world, challenging the limits and expanding our paradigm. Recognition of the weaknesses and organ specific complications allow the clinician to make choices for optimal outcomes. These advancements have allowed outcomes to be optimized.
Expanding the organ donor pool is one solution to increase the availability of organs for transplantation. Increasing the attention to and the use of DCD organs combined with machine and normothermic perfusion is a future strategy to obtain ongoing clinical success in organ transplantation and lower the waiting list mortality.
Lost potential and missed opportunities for DCD liver transplantation in the United States
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Donation after cardiac death(DCD) has been proposed as an avenue to expand the liver donor pool.
We examined factors associated with nonrecovery of DCD livers using UNOS data from 2015 to 2019.
There 265 non-recovered potential(NRP) DCD livers. Blood type AB (7.8% vs. 1.1%) and B (16.9% vs. 9.8%) were more frequent in the NRP versus actual donors (p < 0.001). The median driving time between donor hospital and transplant center was similar for NRP and actual donors (30.1 min vs. 30.0 min; p = 0.689), as was the percentage located within a transplant hospital (20.8% vs. 20.9%; p = 0.984).The donation service area(DSA) of a donor hospital explained 27.9% (p = 0.001) of the variability in whether a DCD liver was recovered.
A number of potentially high quality DCD donor livers go unrecovered each year, which may be partially explained by donor blood type and variation in regional and DSA level practice patterns.
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Citation Excerpt :
Median donor age in the series was 59 years and higher than that typically described in previous series of cDCD livers recovered with SRR.3–5,9,34 Donor age has been identified as a risk factor for ischemic biliary injury in DCD liver transplantation.35–38 Aging induces changes in choleretic function, and injury response in senescent cholangiocytes is impaired.39,40
Postmortem normothermic regional perfusion (NRP) is a rising preservation strategy in controlled donation after circulatory determination of death (cDCD). Herein, we present results for cDCD liver transplants performed in Spain 2012–2019, with outcomes evaluated through December 31, 2020. Results were analyzed retrospectively and according to recovery technique (abdominal NRP [A-NRP] or standard rapid recovery [SRR]). During the study period, 545 cDCD liver transplants were performed with A-NRP and 258 with SRR. Median donor age was 59 years (interquartile range 49–67 years). Adjusted risk estimates were improved with A-NRP for overall biliary complications (OR 0.300, 95% CI 0.197–0.459, p < .001), ischemic type biliary lesions (OR 0.112, 95% CI 0.042–0.299, p < .001), graft loss (HR 0.371, 95% CI 0.267–0.516, p < .001), and patient death (HR 0.540, 95% CI 0.373–0.781, p = .001). Cold ischemia time (HR 1.004, 95% CI 1.001–1.007, p = .021) and re-transplantation indication (HR 9.552, 95% CI 3.519–25.930, p < .001) were significant independent predictors for graft loss among cDCD livers with A-NRP. While use of A-NRP helps overcome traditional limitations in cDCD liver transplantation, opportunity for improvement remains for cases with prolonged cold ischemia and/or technically complex recipients, indicating a potential role for complimentary ex situ perfusion preservation techniques.

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: Research for this paper was done while the author (C.J.) was a National Research Service Award postdoctoral fellow with the Division of Organ Transplantation at Northwestern University, Feinberg School of Medicine under an institutional award from the National Institute of Diabetes and Digestive and Kidney Diseases, 5 T32 DK077662-02 (PI: Michael Abecassis, MD MBA).

: A.I.S. and C.L.J. contributed equally to this manuscript.

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Central Surgical AssociationThe impact of ischemic cholangiopathy in liver transplantation using donors after cardiac death: The untold story

Background

Methods

Results

Conclusion

Section snippets

Patients and methods

Donor and recipient characteristics

Discussion

Am J Transplant

Am J Transplant

Am J Transplant

Am J Transplant

Transplant Proc

Am J Transplant

Transplant Proc

J Hepatol

Am J Transplant

Am J Transplant

Final rule

Fed Reg

Clinical results of an organ procurement organization effort to increase utilization of donors after cardiac death

Transplantation

Donation after cardiac death as a strategy to increase deceased donor liver availability

Ann Surg

Central Surgical Association
The impact of ischemic cholangiopathy in liver transplantation using donors after cardiac death: The untold story