The fate of donor livers allocated via an out-of-sequence expedited placement (EP) pathway has not been previously examined. We determined the originating and receiving United Network for Organ Sharing (UNOS) regions of all donor livers procured between January 1, 2010 and October 31, 2012 and placed out of sequence with UNOS bypass code 863 (EP attempt) or 898 (miscellaneous). We reviewed the early function of these liver grafts and assessed the effect of EP allocation on wait-listed patients at our center. Registrants at our center were eligible to receive 1298 liver offers during the interval studied: 218 (16.8%) of these liver offers bypassed our center and were allocated to other centers and used in patients lower on the match-run list. During the study interval, 560 livers were allocated in the United States by EP. Regions 1, 5, 7, 9, and 10 used the greatest number of EP-placed grafts. Region 1 (New England) used the greatest proportion of all EP livers (33% of all imported EP livers in the United States, P < 0.001 versus all other regions). Graft function data were available for 560 livers placed by EP: 491 (88%) of these grafts were functioning at a mean of 399.5 days after transplantation. In conclusion, the transplantation of livers allocated by means of an expedited refusal code is asymmetric across regions and, in some instances, results in the bypassing of patients with higher wait-list priority but without notification of the bypassed center. Short-term graft function after EP allocation is excellent. Policies governing EP allocation should be created in order to improve access to available organs. Liver Transpl 19:1159-1165, 2013. © 2013 AASLD.
See Editorial on Page 1059
The allocation of donor livers in the United States is predicated on 3 fundamental principles. First, allocation is patient-centric rather than center-based. Second, illness severity is a primary determinant of patient wait-list ranking. Third, organs are allocated locally before they are offered regionally, and if they are declined regionally, they may be offered nationally. Adjustments for special circumstances have been built into this liver allocation process; for example, Model for End-Stage Liver Disease (MELD) exception points are granted to patients with hepatocellular carcinoma. This practice is rigorously tracked to determine its effect on overall organ allocation and utilization. There have been discussions of changes to liver allocation to broaden regional sharing and reduce regional disparities in organ availability; however, expedited placement (EP) has not been a part of these discussions.
During the past 15 years, data collection, verification, and organ allocation tracking have been automated by the use of the UNet and DonorNet Web-based computer systems. A postimplementation analysis of the effect of DonorNet on organ allocation suggests that its implementation has resulted in an overall increase in local and regional organ use.
In the United States, there exists a frequently used but poorly tracked mechanism for liver allocation based on EP by organ procurement organizations (OPOs) to receiving centers. The EP pathway is distinct from the standard allocation pathway governed by the fundamental principles enumerated previously, and it has been designed to facilitate the placement of organs that may otherwise be discarded because of a lack of suitable local recipients. The EP pathway allows OPOs to bypass patients on regional match-run lists and allocate organs out of sequence directly to any US center. OPOs are required to justify out-of-sequence allocation with a variety of codes (see Appendix 1 in the supporting information). For example, bypass codes are used in military allocation and directed donation. More commonly, OPOs use out-of-sequence bypass codes 863 (offer not made because of an EP attempt) and 898 (miscellaneous) when time constraints or experience suggests that local and regional centers will decline the organ. We have defined this form of bypass code use as EP. In standard in-sequence allocation, the local OPO may offer livers to an unlimited number of local centers via DonorNet. After local allocation has been exhausted, the OPO can make regional and then national offers via DonorNet directly to an unlimited number of patients at up to 3 centers simultaneously before organ recovery and at up to 5 centers simultaneously after organ recovery. Current United Network for Organ Sharing (UNOS) policy, however, also permits OPOs to initiate an EP discussion with any center at any time during the allocation process if donor characteristics are likely to fall outside local centers' known selection patterns or after procurement if time constraints require EP to place the organ successfully. This EP discussion can occur even before local offers are exhausted. In other words, using EP placement, OPOs do not have to adhere to standard allocation principles, nor are they required to use DonorNet for the initial notification of the EP offer.
The aim of this study was to critically analyze the distribution patterns and fates of donor livers that were allocated with bypass codes 863 and 898, which are the most commonly used codes for EP. As we have used the term, EP refers to out-of-sequence allocation that bypasses patients who have higher wait-list priority without notification of the center at which they are listed. No such publicly available analysis has been performed previously. In addition, we analyzed the effect of EP on patients awaiting liver transplantation at our own center.
PATIENTS AND METHODS
This study was approved by the institutional review board of the Albert Einstein College of Medicine. Data were obtained from UNOS by a standard data request. We analyzed data for the interval of January 1, 2010 to October 31, 2012 for cases in which a donor allocation resulted in either an offer or a bypass of a patient on our waiting list. We assessed the effects of bypass codes 863 and 898 on our own wait-listed patients through an evaluation of the number of patients bypassed at our center for each liver allocated by the bypass pathway to another patient not on our waiting list. Data were then analyzed to determine the originating and receiving regions of all donor livers procured in the United States and placed with bypass codes 863 and 898; this is our definition of EP for this analysis. Other bypass codes were excluded from this study so that we could focus on interregional EP placement rather than the numerous other bypass options (eg, military allocation). With EP placement, OPOs use bypass codes 863 (EP) and 898 (miscellaneous). An additional code for donor medical urgency (862) can also be used to justify EP, but this was excluded from consideration because it was used for only a small fraction of the total allocation (16 livers during the entire period of analysis). An example of donor medical urgency is donor hemodynamic instability before procurement. Code 898 (miscellaneous) is associated with text comments that OPOs use to explain the reason for bypass. In this data set, when both 898 and 863 codes were entered by the OPO for the same donor, the donor was categorized as 863 for the purposes of this analysis. Whenever there were 2 codes associated with an offer, the offer was counted only once in the data set.
Center-specific data from transplant programs other than our own were not available for this analysis. Finally, we reviewed data on the early graft function of livers placed by EP. The statistical analysis was performed with Stata/SE version 9.2 (StataCorp, College Station, TX).
Patients at our center were eligible to receive 1298 donor liver offers from January 1, 2010 to October 31, 2012. Two hundred eighteen liver offers (16.8%) bypassed our center through the use of code 863 or 898 and were allocated to patients at other centers with lower priority on the match-run list. During this time period, our center did not receive any EP liver offers (direct offers outside DonorNet notification). Because there was no formal notification that these livers were available or that our patients were eligible to receive them, these liver offers could not be evaluated for patients on our waiting list, and acceptance or refusal codes could not be entered for those patients. One hundred seventy-one of these 218 organs (78.4%) were accepted and implanted by the receiving center; 146 of the 171 grafts were identified as functioning with a 1-year graft survival rate of 85% and a mean follow-up of 334 days. Only 6 of the 25 grafts that were reported as having failed after transplantation (<3% of the total) failed during the first week after implantation, and this suggests that 95% of the EP-placed grafts were initially functioning.
On average, 10.7 patients (range = 1-52) on our center's waiting list were bypassed for each organ allocated by EP. Table 1 presents the distribution range of the MELD scores or the status 1 status for the bypassed patients. During the study interval, 31 patients at our center died on the waiting list or were removed from the list because they were too sick for transplantation. Twenty-six of these patients (84%) were bypassed at least once with a liver that was placed elsewhere with the EP pathway. We analyzed the geographic distribution of EP livers during the study interval: 163 (75%) of the livers that bypassed our center originated from regions on the east coast of the United States, which is a geographic area contiguous with our own. Table 2 displays the originating regions of livers that bypassed our center, which is located in region 9. When we analyzed the region of origin for each of these livers, we observed that the majority originated from 1 OPO/donor service area (DSA) within each region.
Table 1. MELD Scores and UNOS Status of Patients at Our Center Who Were Bypassed
Table 2. Regions of Origin of Livers Placed by EP Codes That Bypassed Our Center in Region 9
|1. MA, CT, NH, RI, ME, and eastern VT||0||Not applicable|
|2. NJ, PA, WV, MD, DE, and northern VA||44||70|
|3. AL, FL, GA, MS, LA, AR, and Puerto Rico||72||67|
|4. TX and OK||9||67|
|5. CA, UT, NM, AZ, and NV||28||96|
|6. WA, MT, ID, OR, AK, and HI||6||67|
|7. MN, IL, WI, ND, and SD||3||50|
|8. MO, CO, IA, KS, NE, and WY||9||56|
|10. OH, MI, and IN||2||50|
|11. VA, KY, TN, NC, and SC||45||53|
Between January 1, 2010 and October 31, 2012, 560 livers were allocated and transplanted in the United States with bypass codes 863 and 898; these livers represented 5% of the 11,089 deceased donor liver transplants performed during this time period. Three hundred twelve livers were allocated with refusal code 863, and 248 livers were allocated with refusal code 898. Table 3 shows the originating and receiving regions for livers allocated with EP code 863, and Table 4 shows the originating and receiving regions for EP code 898. Table 5 shows the total number of livers placed with codes 863 and 898. Table 5 also displays the percent utilization by region of all livers allocated with these combined EP codes and the percent utilization by region of imported EP livers.
Table 3. Originating and Receiving Regions of Livers Placed With EP Code 863
Table 4. Originating and Receiving Regions of Livers Placed With EP Code 898
Table 5. Regional Utilization of Livers Allocated by EP Codes 863 and 898
|% of all EP livers|| ||20||8||9||3.9||15||0.1||10||6||13||11||4|
|% of all imported EP livers|| ||33||9||4||2||6||0||13||1||19||12||0.3|
Overall, the majority of livers (235/312 or 75%) allocated via EP code 863 were exported to another region. OPOs in some regions exported most of their 863-allocated livers out of region: regions 2, 3, 8, 9, and 11 exported 93%, 84%, 81%, 79%, and 81%, respectively. In other regions (1, 4, 5, 7, and 10), however, the majority of livers allocated with code 863 (39/62 or 63%) were retained in the same region. Centers in region 1 received 94 of 312 liver offers (30%) in the United States allocated via code 863, and 93 of 235 (40%) of these offers were exported out of the region of origin. Table 4 shows the national allocation of livers placed with EP code 898: unlike EP organs placed with code 863, the majority (165/248 or 67%) of EP organs placed with code 898 remained within their region of origin. Most of the livers originating from regions 2, 3, 6, and 11 that were placed with EP code 898, however, were exported to another region (53%, 52%, 100%, and 70% respectively).
The centers that used the greatest number of intraregional and interregional (imported) livers by EP codes (863 and 898 combined) were located in regions 1, 5, 7, 9, and 10 (Table 5). Centers in region 1 used a greater proportion of EP livers than centers in the other regions: 20% of all EP livers and 33% of exported EP livers (P < 0.001 versus the region with the next highest use of imported livers).
Graft function could be determined for 560 livers placed by EP; 491 (88%) of these grafts were functioning at a mean of 399.5 days after transplantation. Twenty-three of the 82 grafts that failed (4% of the total) failed within the first postoperative week.
Maximizing donor utilization and ensuring the fair distribution of available organs are important but potentially competing goals in the current era of organ shortages. Consequently, systems have been developed to ensure that organ allocation is as efficient as possible, just, and open to public scrutiny. It is important to recognize, however, that the principles guiding organ distribution in the United States are not applied to the largely unexamined EP pathway, which is an additional route for donor liver allocation. The EP pathway exists to facilitate the rapid placement of organs when local centers will not accept them. Current UNOS policy mandates that the Membership and Professional Standards Committee review cases in which livers have been allocated via an EP pathway, although the number of cases and the triggers for review are not known.
The latest report of the Scientific Registry of Transplant Recipients[5, 6] states that “geographic disparity in organ availability remains notable” on the basis of observations of regional disparities in the waiting time, likelihood of transplantation, and wait-list mortality. A recently convened public forum, sponsored by the Organ Procurement and Transplantation Network (OPTN)/UNOS Liver and Intestinal Organ Transplantation Committee, identified several possible ways of improving organ distribution, including share 29 (the regional sharing of deceased donor livers for wait-listed patients with a MELD score of 29 or higher), organ allocation with a system combining the MELD score and the estimated transplant benefit (based on expected posttransplant survival), and the redistricting of UNOS regions into larger super-regions. Although the dialogue regarding this issue is encouraging, there has not been much attention paid to the existence and regulation of donor livers placed by EP codes.
It is debatable whether society benefits more from maximization of organ use or fairness in organ distribution, but we believe that policies can be modified to serve both aims. At the very least, EP distribution and transplantation outcomes for EP organs should be analyzed and made public so that policymakers can make adjustments as necessary. Our analysis has uncovered several issues associated with EP organ placement. The transplantation of livers allocated by means of an expedited refusal code is unequal across regions. Despite the existence of aggressive centers in many regions of the country, 1 region (region 1) was the greatest user of livers placed by EP. The use of EP livers was not proportionate to the mean MELD score of wait-listed patients in the region. The most recent Scientific Registry of Transplant Recipients report indicates that the median MELD score of patients in region 1 was 27, whereas it was 29 in regions 4, 5, 7, and 9, which received fewer EP livers. We have not performed an analysis of donor characteristics (donation after cardiac death or extended criteria donors) as a part of this analysis, and this is a potential limitation of this study because donor characteristics affect the quality of EP-placed grafts; however, the observed graft survival does not suggest that the EP organs were of inferior quality. National graft quality data are highly subjective (biopsy results and the degree of steatosis are 2 examples) and are incompletely captured in the OPTN database. The aim of this study was not to evaluate the donor quality of EP livers but rather to assess overall utilization patterns and their effects on our center's wait-listed patients. Although there may be many reasons that centers in a single region may have used more EP livers than centers in other regions, the high proportion of organs sent from a specific donor region to a specific recipient region suggests the existence of preferential relationships between donor OPOs and receiving centers. These relationships may be as simple as a list of telephone numbers used by OPO personnel to place EP livers quickly to transplant centers known to be aggressive.
Because the activity surrounding EP allocation is not subject to traditional allocation standards, its potential effect on patient outcomes should be evaluated, and this is something that has not yet been done for the nation as a whole. We sought to clarify this issue for our own center. In analyzing our center-specific UNOS data, we discovered that 75% of the donor livers that bypassed our center as a result of EP came from OPOs on the east coast of the United States, some within driving distance of our center. For each EP placement that occurred within the time of this analysis, approximately 11 individual patients at our center with a higher rank on the waiting list, including patients with high MELD scores and status 1 priority, were bypassed without notification, and this deprived these individuals of an opportunity for transplantation. Within the same time interval, 31 patients on our center's waiting list either died or were removed from the transplant waiting list because of “too sick to transplant” codes; 26 (84%) of these patients were bypassed at least once with a liver that was placed elsewhere via the EP pathway. Our results indicate that 2 of the bypassed patients were listed as status 1 at the time of bypass, and others had MELD scores that may have justified EP grafts. A limitation of our analysis, however, is that for most patients on our list, the bypass event might have occurred at any time during the waiting period, and this makes it possible that the EP offer would have been declined. Nevertheless, because we never received information about the donors, it would be difficult to retrospectively assess whether or not these organs would have been used for a given patient. We contend that some of the patients on our list may have been put at a disadvantage by the current EP pathway.
UNOS requires OPOs to notify centers when their wait-listed patients have been bypassed during organ allocation (see Appendix 1 in the supporting information). At our own center, we have never received notification that one of our wait-listed patients has been bypassed. We believe that transplant centers should be able to determine that their patients have been bypassed and be told the fate of those livers in a fashion similar to the center-specific organ declination reports that are accessible on UNet. This type of data reporting would permit centers to potentially modify their donor selection patterns to encourage wider participation in EP allocation, even though participation at this point is entirely at the discretion of the OPOs.
It is important to note that the 1-year graft survival of livers placed by EP was 85%, which is similar to overall national 1-year graft survival.[5, 6] Less than 3% of the EP grafts failed within the first week after transplantation, and this potentially indicates that there was no significant short-term quality issue with grafts that were turned down locally and eventually placed elsewhere. Recent publications related to imported livers have validated these observations.[8-10] Although it might be postulated that these results were possible because EP livers are open offers and are given to patients with lower MELD scores, the observed 1-year graft function of livers allocated by EP is still surprisingly good and should be studied further. Distance and its effect on graft function have been an argument against broader regional sharing. Our observations may guide planners who are discussing the creation of broader sharing regions because many of the organs allocated by EP traveled long distances but still functioned well.
We recognize that OPOs are under pressure to place any transplantable organ and that in many instances when organs are turned down locally and regionally, the “clock starts ticking”, especially if the offer is made after procurement. It is a great achievement that during the time period analyzed, nearly 600 organs turned down by local centers were eventually allocated to another regional or nonregional center via EP and that these organs functioned well at 1 year. These livers, however, bypassed patients who in many instances were in regions or DSAs contiguous with OPOs that used these bypass codes and, at least in our own center's experience, had higher MELD and priority scores than the patients who received these grafts (including 2 status 1 patients). Moreover, programs were not routinely notified that their patients were being bypassed. A potential weakness of our analysis is that we have focused on the absolute number of EP livers placed by region rather than the rate of EP liver allocation as a proportion of the total livers procured. We also have focused this analysis not on individual OPOs or DSAs or, for that matter, on individual receiving transplant centers but rather on the interregional flow of organs. Finally, we do not know the in-sequence/out-of-sequence allocation ratio for livers that were exported by region.
The disparities in the allocation and utilization of EP livers identified in this study clearly indicate that the processes surrounding EP liver allocation across regions could be more transparent. Potential adjustments to the EP liver pathway should be discussed at regional and national forums. Currently, it is completely at the discretion of the OPO to identify livers that are suitable for EP as well as the centers that might accept these organs on a consistent basis. We believe that standardized criteria and policies regarding the identification of livers suitable for EP placement should be as robust as policies for identifying appropriate transplant recipients. Although the cost of any major programming change to UNet is likely to be significant and an assessment of the potential cost is beyond the scope of this article, cost concerns should not preclude a preliminary discussion and modeling of potential policy changes. The phenomenon of EP by OPOs may be based on past experience with aggressive centers (and, conversely, with nonaggressive centers). Transplant centers in the United States, however, do not have a fixed size or donor selection pattern. Over time, some centers may become more aggressive or less aggressive on the basis of many factors but ultimately on the basis of their list of available candidates for EP livers. Smaller centers may have smaller lists and, therefore, less need to use livers allocated by EP at any given time because of a lack of suitable patients, but they may on a case-by-case basis use an offer if a patient's condition merits it. It is our contention that the informal, subjective reputation of a receiving center that routinely accepts EP livers is based on the interpretation of the donor OPO and could be biased by factors such as ease of communication, past history, and other nonclinical factors.
One potential reform to the allocation system was recently proposed by Lai et al., who suggested that if a liver has been refused at both local and regional levels, centers with a prestated interest in being notified of EP liver offers should be simultaneously informed through DonorNet, with placement to the center with the highest ranking provisional “yes”.
An example of the feasibility of the regional notification of import EP offers is a statewide project (currently being piloted with a grant from the NY State Department of Health in region 9) in which the local OPO (the NY Organ Donor Network) serves as the local exchange for all import offers to region 9. Calls for EP are placed directly to OPO call center personnel, who then simultaneously notify all region 9 centers of the offer to ensure transparency and equal access. Region 9 centers then have the option of ignoring the offer (assumed declination) or placing a provisional yes on the match-run list, with a time limit of 45 minutes from notification to response (ensuring efficiency). Once any region 9 center has placed a provisional yes, the call center has the authority to accept the import offer on behalf of the region with a request for local backup, and ultimately, the highest ranking in-sequence patient with a provisional yes in region 9 will receive the organ to ensure fairness. This pilot project was initiated only during the last quarter of 2012, so sufficient data do not yet exist on the number or demographics of offers received and used, although this may be reported in the future. A national algorithm as described previously could be devised, although the implementation of this algorithm would be anticipated to be more difficult on a national scale. The ultimate goal of any reform would be more efficient electronic matching between donor OPOs and accepting centers based on accepted allocation standards (eg, MELD priority) without the need for OPOs to manually hunt for accepting centers for organs that could not be placed locally. Organs could also be easily tracked, and more organs potentially could be used. Ultimately, it is our belief that relatively minor changes might promote greater progress toward achieving the goals of the final rule, whereby the best use of donated organs and enhanced patient access to transplantation would be possible with assurance that access to transplantation would not be based on geography.