Integrating data regarding liver offers with donor and candidate characteristics, we found that the vast majority (84%) of wait-listed candidates who died or were delisted at a MELD ≥15 had received liver offers that were ultimately transplanted into lower priority candidates. More surprisingly, these candidates received not just one or two but a median of six liver offers during their time on the wait-list. These findings suggest that wait-list mortality is not simply a result of not having the opportunity for transplantation, as many of us assume. Rather, wait-list mortality appears to result from opportunities for transplantation that were declined.
Although each declination is associated with a specific refusal code, the dominant use of a single code “donor quality or age” – even when the liver appears to be of high quality – strongly suggests that the UNOS/OPTN data does not accurately or fully capture the true refusal reason. However, we found no difference in the risk of graft failure among high quality livers that were accepted on the first offer compared to high quality livers that were turned down at least once, suggesting that there were no systematic differences inherent to the fact that they were refused, despite the fact that the most common refusal code registered in UNOS was “donor age/quality. There are undoubtedly reasons in addition to a single unfavorable donor factor, such as recipient-donor interactions or the transplant centers’ philosophy about the utility of transplantation given certain donor and recipient characteristics, that drive the real-time decisions to decline a liver offer. The nuances of these refusals cannot be determined in the absence of more granular, center-level data.
Nevertheless, in considering the rhythm and patterns of daily clinical practice, we suggest that there are three major categories of factors that influence this complex and dynamic decision:
For most patients with cirrhosis, the progression of liver disease is a nonlinear process characterized by sudden deteriorations related to events such as variceal hemorrhage, spontaneous bacterial peritonitis, or hepatorenal syndrome. During the course of these events, candidates may be perceived to have excess peri-operative and short-term post-transplant risk (e.g., sepsis) rendering the candidate temporarily or permanently unsuitable for transplantation necessitating refusal of liver offers. Second, a candidate may be actively listed but still completing the pre-transplant evaluation and therefore, are essentially not ready for transplantation. It is also a possibility that transplant clinicians perceive candidates to be “well enough” to wait for a better graft, especially when faced with an offer of lower quality. Finally, candidates, themselves, can refuse a transplant opportunity presented to them by their transplant physician secondary to logistical constraints, concerns regarding donor quality, or non-medical limitations.
The quality of donor livers has been decreasing over time (4
), with only 29% of livers transplanted during our five-year study period meeting the definition of high quality. We have increasingly sophisticated knowledge of interactions between donor characteristics and recipient outcome, as seen with HCV-infected recipients receiving older donor livers (5
) and possibly with DCD livers (6
). Finally, there is a strong mandate that any and all aspects of a donor that pose increased risk must be fully disclosed to and discussed with a potential recipient. This heightened awareness of all dimensions of donor risk likely discourages acceptance of non-ideal transplant opportunities.
The current regulatory environment focused on transplant center performance and outcomes may, consciously or subconsciously, influence offer acceptance versus declination decisions. This may be especially relevant for low volume transplant centers for whom even a small number of poor outcomes associated with grafts that have been declined by other centers (most often for low quality) may make a relatively large difference in the center’s perceived performance (8
). Moreover, the financial implications of transplant decisions are substantial, particularly if the candidate has high disease severity and/or the donor liver is of suboptimal quality (9
). Finally, factors such as competition with other centers and availability of surgeons and operating room space may also play a role in the decision to accept offers at certain times.
Understanding the real-time factors involved in these decisions is vital to improving the wait-list process for liver transplant candidates. While some of the factors are beyond control, others can be managed. For example, centers should encourage wait-list candidates to complete their liver transplant work-up (e.g., cardiac testing, age-appropriate cancer screening, tuberculosis testing) as expeditiously as possible to avoid having liver offers turned down simply because they are not ready. Patients with a MELD ≥ 15 should be thoroughly educated about the unpredictability of death on the wait-list and their survival benefit of transplantation with any graft relative to continued waiting on the list (10
) in order to reduce patient refusal of otherwise suitable organs. This education effort might include a prospective assessment of the individual candidate’s willingness to accept increased donor risk in exchange for more expeditious transplantation (thereby reducing wait-list mortality), as has been proposed by Volk et al (11
). Given the increasing risk profile of deceased liver donors, efforts should be made in the transplant community to reduce the stigma associated with non-ideal livers and set realistic expectations for wait-listed candidates. Perhaps, liver offer acceptance practices should be taken into consideration in assessing center performance, as a means of encouraging centers to accept more livers for their candidates.
In conclusion, our data demonstrate that the current liver allocation system has provided one or more transplant opportunities to nearly all candidates prior to death/delisting. Therefore, simply increasing the availability of deceased donor livers or the number of offers may not substantially reduce wait-list mortality. It is worth noting that all centers/physicians are provided with the same information about the donors, so differential decisions regarding declining or accepting a liver offer cannot solely be based on donor factors. Efforts must be directed at reducing offer declination rates through identification of modifiable barriers that may exist at multiple levels – candidate, physician, center, as well as donor – to proceeding with timely transplantation to avoid death or delisting as the terminal wait-list event.