In patients who do not accept DCD and wait for DND-SLKT, the time to greater than 95.0% of patients being transplanted or dying was 2.71, 2.05, and 0.49 years for those with MELD scores of ≤20, 21–30, and >30, respectively. The median time to transplant for these groups was approximately 240, 85, and 15 days (Figure 5). From the literature, median time to transplant is 82 days for MELD <30 and 14 days for MELD score of 30 to <40, confirming external consistency.22 For those who declined DCD and chose to wait for DND-SLKT, 22.7%, 20.9%, and 29.1% of patients with base MELD scores of ≤20, 21–30, and >30 died on the waitlist, never undergoing SLKT.
Extending the time horizon out to 20 years did not change the dominant strategy for each MELD category, (Table S2, SDC, http://links.lww.com/TP/B632).
Worldwide, the transplant waitlist continues to grow with many more recipients waiting for organs than available donors. The number of patients on the waitlist in the United States has increased by 516% since 1991, with a relatively smaller 229% increase in donors.23 A variety of strategies to mitigate the organ shortage have been adopted, including an international effort to expand the use of DCD organs. It has been proposed that increased use of DCD organs could expand the donor pool twofold to 4.5-fold.24 The concern is that DCD organs may be of inferior quality to DND organs. Although controversial, liver transplant from DCD donors has comparable outcomes with DND liver transplant,8,9,25 especially in those with higher base MELD scores.11 In kidney transplant, DCD organs have similar long term outcomes as for DND organs, despite a higher rate of delayed graft function.12 The implications of DCD SLKT have been less rigorously studied. One cohort study suggested equivalent outcomes with DCD and DND SLKT at 1 year posttransplant, however this study included only 5 DCD SLKT recipients.25 A subsequent analysis demonstrated reduced 5-year patient and graft survival with DCD versus DND SLKT (56.7% versus 68.5%; 89.4% versus 97%; 84.2% versus 93% for patient, death-censored liver, and death-censored kidney survival, respectively).14 Despite being inferior to DND SLKT, 5-year patient and graft survival for DCD SLKT remained greater than 50% suggesting this may still be a reasonable option for transplant given the challenges with organ scarcity.14 Identifying which patients if any would benefit most from accepting a DCD SLKT was the objective for this medical decision analysis.
This study demonstrated that from the patient perspective, the decision of whether to accept or decline a DCD SLKT is dependent on a patient’s underlying disease severity as indicated by their MELD score. In those with lower MELD scores (MELD ≤30), the preferred treatment strategy is to not accept DCD SLKT and instead wait for better DND SLKT organs. This likely reflects the relatively lower waitlist mortality and higher baseline health utility in this less sick population. Conversely, for those with a MELD score >30, the strategy of choice is to accept a DCD SLKT now given the much higher waitlist mortality and lower health utility for this sicker group, irrespective of their higher transplant rate. This finding was robust across a number of sensitivity analyses varying waitlist mortality and transplant rate (for SLKT and kidney alone), as well as post-SLKT patient, liver, and kidney graft survival. All sensitivity analyses were coherent with expected conclusions suggesting the model was internally consistent. Median time to transplant for those who declined DCD SLKT and waited for DND organs was similar to epidemiologic data from another study not used in model derivation,22 which suggests the model was also externally consistent, acknowledging that not all centers perform SLKT, and results may vary between centers with high and low SLKT transplant rates.26
From the patient perspective, waiting for relatively better DND SLKT organs may be beneficial for those with lower MELD scores, however this conflicts with what is best from a societal perspective. For liver transplant in the United States, DCD organs have independently been associated with a nearly fourfold increase in the odds of organ nonuse; a trend which has increased over time.27 Declining organs simply for being of DCD origin has the potential to worsen the organ shortage and will contribute to the growing transplant waitlist. From a societal perspective, the utilization of all organs with a reasonable expectation for graft survival would be the preferred approach to maximize the donor pool and facilitate more transplantation. If there is no alternative candidate, the risk of declining DCD SLKT is one less person being transplanted and removed from the transplant waitlist. There is a benefit to the individual of accepting a DCD SLKT for those with a MELD >30, but not lower. Patient’s with higher MELD scores and more advanced disease are currently prioritized for LTA/SLKT given their high waitlist mortality rates, so are likely already triaged for whichever organs first become available (DCD or DND). Thus, this issue more so applies to DCD SLKT organs when there are no recipients with MELD score greater than 30. Although from the patient perspective declining these organs would be the preferred strategy in terms of quality of life, the incremental value of waiting for a DND SLKT is small (≤0.54 QALYs over 10 y) and the societal cost of not reducing the waitlist is large. As such, DCD SLKT should still be considered in these patients if no higher risk candidates (MELD score, >30) are available.
This study has limitations. It was assumed patients with liver graft loss would not be retransplanted and as such, both death and liver graft failure were treated as a composite outcome with a utility of 0. While retransplantation is the only viable option for liver graft failure, it has been associated with a high mortality rate (1 y patient survival of 45% for 2nd transplants and 1 year survival 24% for 3rd transplants)28 and the benefit of retransplantation has been proposed to be limited to certain healthier subgroups.29 Despite this, repeat liver transplant occurs in 5% to 19% of all liver transplants30,31 and could be considered in a more complex future model. Inclusion of an option for repeat liver transplant would have favored the accept DCD arm given the reduced graft survival rates observed with DCD SLKT. We also assumed that those waiting for SLKT could not undergo LTA, although it is known that about 12% of the population with combined liver-kidney failure will actually undergo LTA.1 The indications for SLKT versus LTA in patients with varying degrees of renal insufficiency are not well established, but most centers are striving to achieve SLKT in appropriate candidates as a way of increasing donor tolerogenicity and improving kidney graft survival compared with KALT.32 Parameter uncertainty for posttransplant outcomes was addressed in multiple sensitivity analyses. It should be noted that patients with ESLD and advanced kidney disease generally have a MELD score of 20 or greater; however, patients with MELD score <20 may still undergo SLKT.33 Based on available literature regarding both health states and transition probabilities, we chose to stratify our model by MELD score, not Na-MELD. Although Na-MELD has been shown to have better predictive accuracy for 90-day mortality than the original MELD score, the difference between the 2 is small and of uncertain significance (c-statistic 0.883 for Na-MELD and 0.868 for MELD) with 93% crossover between the 2 scores.20 Additionally, an Na-MELD based LTA/SLKT allocation system was only adopted in the United States in 2016 and thus was not in use during the 2002 to 2011 period from which our transition probabilities were derived.34 Thus, given the available literature we felt that use of the MELD score was clinically appropriate, however, to confirm stability of our results, we did explore a range of health states and transition probabilities for each base MELD score (encompassing corresponding Na-MELD); none of which altered our result. Results based on Na-MELD score would not be expected to significantly differ from those presented here, however this may be an area for future study. It has been suggested that given the heterogeneic phenotype of the MELD score, MELD score in and of itself may not correlate well with quality of life (QOL).35 Ascites and encephalopathy have been associated with worse QOL, but the presence of these decompensations is not well captured by the MELD scoring system and therefore, there may be uncertainty around the utilities assigned for each base MELD category.35 This issue was addressed using a 1-way sensitivity analysis varying the utilities for each MELD category assessed, and could potentially be explored in a future analysis that incorporates the baseline Child-Pugh score in addition to MELD. We did not have data available to examine more granular cut-points for baseline MELD scores. Our study demonstrates that the transition point where not accepting and accepting a DCD SLKT lies somewhere between a MELD score of 21–30 and MELD score >30, but we did not have the data available to determine the exact threshold where this decision changes. Lastly, it is important to acknowledge that while this model was designed to explore patient QOL related to DND versus DCD SLKT, it does not consider other patient factors that may motivate a patient to accept the first available organ; for example, medical expenses or lost wages while on medical leave. Extrinsic patient motivators for accepting an organ with a shorter wait time would be expected to favor acceptance of DCD organs.
In summary, patients with a MELD score of ≤30 benefit from waiting for a DND SLKT given their relatively low waitlist mortality. In patients with a MELD score >30, however, accepting a DCD SLKT is the preferred treatment strategy given the reduced QOL and high mortality on the SLKT waitlist. Declining a DCD SLKT may not be the strategy of choice from a societal perspective, however, as it has the potential to result in higher organ discard rates and longer transplant waitlists. For lower MELD scores, the societal and individual perspectives regarding DCD SLKT are conflicting; however, it should be noted that the incremental value of declining DCD SLKT in patients with lower MELD scores is small, whereas the societal risk may be large.
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