At a glance Current policy Candidates on the waiting list for a liver transplant are ranked according to their medical urgency using model for end-stage liver disease (MELD) and pediatric-end stage liver disease (PELD) scores. If candidates are particularly urgent, they can be listed at Status 1A or, if they are a pediatric candidate, they can also be listed as Status 1B. The MELD score is used for all liver transplant candidates age 12 and over. It is calculated using four laboratory variables. However, research has shown that the female candidates are disadvantaged in the current system and the MELD score’s ability to measure medical urgency can be improved. The PELD score is used for all liver transplant candidates under the age of 12. It is calculated using five objective variables. PELD has not been updated in more than 20 years and its ability to measure waitlist death has decreased since the time it was implemented. In order to be listed as Status 1A or Status 1B, liver transplant candidates must meet specific criteria to ensure they need the priority status. Candidates listed as Status 1A or Status 1B are sorted based on their blood type compatibility with a donor and time waiting at Status 1A or Status 1B. Supporting media Presentation View presentation Proposed changes MELD score Add sex and albumin to the MELD score calculation Adjust the MELD score for female candidates, whose kidney function is not accurately captured Update the coefficients for the existing variables in the MELD score PELD score Add a creatinine variable Make age and growth failure continuous variables Update variables already in the PELD Account for age-adjusted mortality for pediatric candidates Status 1A Update the definition of hepatic encephalopathy Status 1B Update criteria to qualify for Status 1B for candidates with chronic liver disease Update points used to sort candidates within the status so that more urgent candidates are ranked higher Liver and Intestine Candidates listed for liver and intestine will receive pediatric priority if they are registered prior to turning 18 National Liver Review Board (NLRB) Update guidance to reflect changes in criteria for exception requests Anticipated impact What it's expected to do Update the liver allocation system to ensure that liver transplant candidates are appropriately sorted and ranked according to their medical urgency for transplant What it won't do Change who is eligible to receive a liver transplant Terms to know Candidate: An individual on the organ transplant waiting list. Transplant program: An organ specific facility within a transplant hospital. Hepatic Encephalopathy: A nervous system disorder brought on by severe liver disease. When the liver doesn't work properly, toxins build up in the blood. These toxins can travel to the brain and affect brain function. Hepatoblastoma: A rare tumor (an abnormal tissue growth) that originates in cells in the liver. It is the most common cancerous (malignant) liver tumor in early childhood. Guidance Documents: Documents that provide more information to transplant programs and NLRB members to use when making decisions on exception requests. Model for End-Stage Liver Disease (MELD): The scoring system used in allocation of livers to candidates who are at least 12 years old. Pediatric End-Stage Liver Disease (PELD): The scoring system used in allocation of livers to candidates who are under 12 years old. National Liver Review Board (NLRB): A review board of members drawn from a nationwide pool of liver transplant physicians and surgeons, who review exception requests from transplant programs for candidates whose automatically calculated model for end-stage liver disease (MELD) score or pediatric end-stage liver disease (PELD) score does not accurately reflect the candidate’s medical urgency for transplant. Standardized exception: A exception with criteria outlined in policy that is automatically approved when submitted and is not reviewed by the NLRB Creatinine: Creatinine is a chemical compound produced by the body when breaking down muscle. It can be used to measure kidney health. Albumin: Albumin is a protein found in a person’s blood and helps transport hormones, enzymes, and medicines throughout the body. It is produced by the liver. Low albumin levels can be a sign of liver disease. Click here to search the OPTN glossary Comments UC San Diego Health Center for Transplantation | 03/23/2022 CASD agrees that while MELD-Na is still a useful predictor of waitlist mortality, the modifications proposed under MELD 3.0 seems to reasonably reduce the sex-based disparity impacting women in the current liver allocation system, improve overall performance in predicting risk of waitlist mortality for all liver transplant candidates and continues to use objective, widely-available clinical values without creating additional burden for programs. Although not directly impacted, CASD also supports the proposed modifications for Status 1A as it creates a more objective and clinically-relevant definition of hepatic encephalopathy which is generally difficult to define in pediatric populations; for Status 1B, the proposed updates to the criteria for a pediatric candidates to qualify for Status 1B priority seem appropriate and better ranks candidates based on their diagnosis and risk of mortality. We fully recognize that further modifications may be appropriate as new data and experience become available and applaud the Committee’s ongoing efforts and advocacy to further refine and improve the MELD/PELD system. Anonymous | 03/23/2022 As the mother of a 2-time liver transplant recipient (female) who was 15 at the time of first listing and 21 at the time of second listing, I am familiar with some of the difficulties and disadvantages faced by young females in attaining a MELD score that is useful. I am in favor of the changes as proposed. Sarah Bernards, Sridhar Tayur, and Neil Mehta | 03/23/2022 Comment on MELD 3.0 from Sarah Bernards, Sridhar Tayur, and Neil Mehta We agree that there is an urgent need to address the persistent sex-based disparities in liver transplant outcomes. The number of “support” votes in these comments shows the LT community agrees. However, it is important to choose a solution that will be most effective at addressing this issue. The fact that there is little “strong support” likely reflects this hesitation. Gender may actually be a surrogate for height (doi: 10.1111/ajt.15644). For women, waitlist mortality decreases as height increases (MELD 3.0 manuscript). Furthermore, gender can change across the lifetime and is not binary male/female. In contrast, height is a fixed variable in the adult population. So, it may not make sense to award additional points to all women, but rather, by height. In the attached abstract (manuscript under review), we propose an alternative solution of awarding additional points based on height. Finally, the inclusion of albumin in the MELD 3.0 score is somewhat problematic as albumin is a highly manipulable variable. LT candidates are routinely infused albumin, especially the sickest patients. Including albumin in MELD 3.0 could artificially suppress the MELD scores of those with greatest urgency for LT. Attachment Transplant Administrators Committee | 03/23/2022 The Committee thanks the OPTN Liver and Intestine Transplantation Committee for the opportunity to provide comment on their proposal Improving Liver Allocation: MELD, PELD, Status 1A, and Status 1B. The Committee supports the proposal, recognizing the sponsoring committee’s work in addressing disadvantaged female liver candidates. Region 6 | 03/23/2022 Sentiment: 2 strongly support, 8 support, 1 neutral/abstain, 0 oppose, 0 strongly oppose. Comments: An attendee commented that the MELD calculation has underserved women for 10-15 years. He supports this proposal because it resolves the disparity between men and women. Another attendee noted that patients with smaller statures may still be waiting longer. The same attendee also commented that some patients could be disadvantaged if albumin levels were manipulated. Attendees discussed how these changes will affect allocation for MELD exception patients, particularly those with hepatocellular carcinoma. An attendee thanked the Committee for engaging the Pediatric Committee, and hopes liver splits will increase or be incentivized in some way. An attendee asked about the rationale for using current gender versus birth sex, and expressed concern that gender identity could be used to advantage a patient on the waitlist. Another attendee noted hormonal therapy used during gender transition may change muscle mass of these individuals. Humana | 03/23/2022 Humana supports the proposed changes to the MELD and PELD scores as the updates could lead to improved allocation scores and reductions in waitlist mortality. Anonymous | 03/23/2022 I am writing this anonymously: 50 year old patient, stage 3 liver cirrhosis, current MELD score between 20-25 I worked with the Liver Transplant Team at one of the two centers in my geographic area from Jan 2020-Feb 2021 to be considered to be on the liver transplant wait-list. After adhering to every request whether it be blood work or numerous procedures: mastectomy, colonoscopies, endoscopies, MRI'S, paracentesis, I ate right and exercised; I was declined for liver transplantion. I was claimed to be noncompliant. I'm still unsure to this day how I was deemed noncompliant, however, I have a thought. 3 weeks after having my mastectomy Nov 2020), I began a new job. My health deteriorated quickly, and I was admitted to my local hospital Dec 2020. It would be important to mention my medical record for this visit is over 600 pages, though some are repetitive. Only after recently reviewing my medical records for SSI disability, I learned how dire the situation was. This is due to a number of factors: I was admitted during the height of the COVID-19 pandemic, my amonia and lactic acid levels were elevated (later learning about signs of Hepatic Encephalopathy), platelet count: 25. I was floored; had I not been a Medical Technologist for over 20 years, who runs patient samples daily, the average person may not (most likely not, unless explained) know this. My ICE was never contacted and numerous attempts to contact the Liver Transplant Team went unanswered, until my support person found the phone number of the Dietitian????? A month after being released and resigning from my work position to focus more on my health, I received the letter stating I was non-compliant. I was at a complete loss and basically gave up until today. I don't know why I decided to wake up and search yet again for options. Your public comment forum closes today, I saw it as an opportunity to share my experience and my continued struggle to live the best quality of life I have left. I had never felt I had a patient advocate at that facility. Little to no contact, responses late or not at all, yet I was held to the highest of standards (understandably so). I am my own patient advocate and reaching out in the hopes to help others in similar scenarios. American Society of Transplantation | 03/22/2022 The American Society of Transplantation is supportive of the need to improve the MELD and PELD calculations and offers the following comments for consideration: We agree that the addition of sex to the MELD score calculation and the cap of creatinine at 3.0 mg/dl is a step forward to reduce the gender disparity and it will translate into transplanting more female candidates making the allocation system more equitable. We are significantly concerned about the use of albumin in the MELD 3.0 equation due to variability in serum albumin levels that may result from acutely ill hospital patients receiving IV albumin. This may unintentionally cause practitioners to question whether to infuse IV albumin when indicated, due to concerns regarding disadvantaging their patients. While albumin is an indicator for hepatic synthetic function, there are non-hepatic etiologies for albumin-wasting conditions such as nephrotic syndrome or protein-losing enteropathies that could falsely elevate candidates’ MELD scores. Questions were also raised regarding which of many albumin levels would be allowed to be entered for the purposes of the MELD calculation. AST strongly recommends consideration of alternative markers that are not limited by these issues. Creatinine is a very poor marker in patients with chronic liver disease. We would recommend exploring the use of different measures to estimate GFR that take into account the presence of chronic liver disease. There are likely more criteria that should be considered, e.g., bleeding episodes in pediatrics. It will be important for the OPTN to follow the impact of these changes on waiting time for candidates, particularly children, with metabolic liver disease. Attachment Minority Affairs Committee | 03/22/2022 The OPTN Minority Affairs Committee thanks the OPTN Liver and Intestinal Organ Transplantation Committee for the opportunity to comment on Improving Liver Allocation: MELD, PELD, Status 1A and Status 1B. The Minority Affairs Committee supports modifications to the PELD, including removal of the MELD/PELD 25 threshold for Status 1B, as more than half of pediatric patients are transplanted with an exception. The Committee also supports changes to encephalopathy in Status 1A and agrees that diagnosis in young children is difficult and unreliable. Anonymous | 03/22/2022 I am a 71-year-old patient with Primary Sclerosing Cholangitis. Because I'm fairly healthy, I am not yet a candidate for transplant, and I hope I stay that way. But I'm very concerned that the transplant process be fair and efficient. The proposed changes head in that direction, and I support them. Region 2 | 03/22/2022 6 strongly support, 11 support, 6 neutral/abstain, 0 oppose, 0 strongly oppose - A member noted that the use of creatinine in PELD could disadvantage infants and young children if it is not age adjusted. Anonymous | 03/21/2022 I am in end stage liver disease and currently listed. My meld is low because my kidney function is still good. I suffer from HE, low albumin and ascites. If they took my albumin into account my meld would go up considerably. Region 11 | 03/21/2022 Sentiment: 4 strongly support, 5 support, 4 neutral/abstain, 0 oppose, 0 strongly oppose. Comments: Overall the region supported the proposal. An attendee commented that it is important that “sex” is clearly defined. Region 7 | 03/21/2022 Sentiment: 3 strongly support, 11 support, 2 neutral/abstain, 0 oppose, 0 strongly oppose. Comments: Members of the region support the proposal, and had a few comments. One member thanked the committee for being inclusive and considering transgender patients. With creatinine values being related to birth sex how does the committee propose determining MELD for transgender patients? Another member expressed support of the proposal and noted that reducing the number of exceptions is needed, as exceptions represent a gap in policy. Another member noted support for adjusting data analysis for female creatinine levels to provide equal analysis compared to males. They also noted for committee consideration is whether the age cut off for PELD needs to be adjusted given that almost two-thirds of pediatric patients are listed with an exception. Lastly, another member has concerns that the current MELD and PELD scores use creatinine rather than a race neutral eGFR. OPTN Pediatric Transplantation Committee | 03/20/2022 The Pediatric Committee thanks the OPTN Liver & Intestine Committee for the opportunity to review their public comment proposal. The Committee provides the following feedback: The Committee generally agreed with the proposal. They appreciated the age-adjusted mortality since it allows room for the PELD score to be adjusted overtime without having to rebuild the whole system and the inclusion of creatinine in the PELD score, although they worry it could disadvantage those with growth failure. The Committee worries that these changes were never modeled and are concerned about accuracy. The Committee emphasized the importance of their participation in post-implementation monitoring of the impact of this proposal – specifically to track pediatric waitlist time, transplants, mortality on the waitlist and post-transplant, and graft loss after the proposal, with consideration of further adjustment to the PELD score in the coming years as accurate data on its impact becomes available. Region 1 | 03/18/2022 Sentiment: 3 Strongly Support; 7 Support; 1 Neutral/Abstain; 0 Oppose; 0 Strongly Oppose. Comments: Overall the region supported the proposal. One attendee shared their agreement with the PELD changes, particularly the 1A and 1B changes. A member encouraged monitoring of the system to ensure there are no untoward outcomes that result from including albumin in the calculation. Another member also expressed concern with the potential for manipulation with the use of albumin in the MELD equation. Society of Pediatric Liver Transplantation (SPLIT) | 03/17/2022 The Society of Pediatric Liver Transplantation (SPLIT) strongly supports this proposal to improve equity and efficiency of the allocation system for pediatric liver transplant candidates on the waitlist. PELD’s accuracy for predicting waitlist deaths has long been recognized as inadequate. The proposed PELD-Cr changes including the integration of the creatinine in the PELD score and other changes which will improve the prioritization of children on the liver waitlist and reduce reliance on exception points. The MELD 3.0 will maintain equity for female and male adolescents, which is appropriate based on current data, thus avoiding disparity in adolescents. We appreciate that it will also integrate the albumin, to improve predicting mortality risk. Updating the hepatic encephalopathy definition will assure status 1A is granted to the pediatric transplant candidates without delay in patients with INR in the 1.5-2 range. This aligns with current pediatric practice – in the experience of our community and as recommended in recent consensus guidelines by NASPGHAN. However, we also recognize that not every child with an INR of 1.5-2 needs a liver transplant; their acute liver injury may still be recoverable and ongoing care and consideration of disease trajectory by experienced pediatric hepatology is crucial to providing appropriate care of these children. The status 1B proposal aims to prioritize patients with chronic liver disease, over patients with tumor or urea cycle disorders/organic acidemias (inborn errors of metabolism) by assigning diagnosis points. We believe that patients with acute on chronic liver failure should be further prioritized over patients from all other categories given the increased risk of mortality in this patient population. We encourage UNOS to move forward with implementing these updates as soon as possible, as long delays in implementation will lead to disease complications and deaths for children waiting liver transplant that are preventable with timely transplant. Long-term monitoring of the impact of these changes – and consideration of further adjustments should their intended impact not be recognized - will be critical to optimizing outcomes for children and other vulnerable populations. This is the first update to PELD since it was implemented originally 20 years ago. Given the small number of children on the waitlist, SRTR’s predictive modeling system (LSAM) is not accurate in predicting the true impact on changes like this to pediatric allocation; due to this, SRTR did not do LSAM modeling for predicted impact of the PELD score. This makes long-term post-implementation monitoring of the true impact on pediatric deaths, transplants and other key outcomes – paired with consideration of additional adjustments (e.g. recalibration of variable values based on post-implementation data) – critical in the years to come. Post-implementation monitoring for geographic disparities and reliance on exception requests will be important to include. We appreciate UNOS’ intention to reduce pediatric waitlist deaths and increase transplants with this proposal. But we also encourage UNOS and the Board to plan for additional adjustments based on real-world post-implementation data to ensure that the system continues to meet children’s needs. Region 9 | 03/17/2022 Sentiment: 2 strongly support, 7 support, 3 neutral/abstain, 0 oppose, 0 strongly oppose. Comments: One member had concerns about including albumin in the MELD calculation, noting that some patients get albumin supplements and would have an inaccurate albumin level. American Society of Transplant Surgeons | 03/17/2022 American Society of Transplant Surgeons supports. Attachment Anonymous | 03/08/2022 More DCD liver transplants should be performed. Region 3 | 03/02/2022 • Sentiment: 3 strongly support, 12 support, 3 neutral/abstain, 0 oppose, 0 strongly oppose • Comments: An attendee recommended the Committee consider how MELD 3.0 could impact the Median MELD at Transplant (MMaT) scores. Rose Kasper | 02/24/2022 Science is changing more rapidly than allocation rules. Pancreas and liver patients are starting to have some common attributes. Metabolic and/or mitochondria issues affect both. Switzerland thru AASLD is ahead of US in this science. Patients in the US are held to MELD and told to get exceptions. Doctors aren’t trained in this area yet so patients are labeled NASH but it is not NASH. Fatty liver is being caused by the metabolic and/or mitochondria issues but does not react the same. MELD is not a indicator of the disease. Vitamin regulation in both the pancreas and liver is a root cause of the fat deposits-they are the recepients not the cause of the disease. I think we are too involved in naming conventions rather then root cause analysis. If you can get to root cause then you can treat symptoms. The naming convention being debated is MAFLD or mitochondria associated fatty liver disease -two different root causes but similar symptoms but in US called an arm of NASH-there are differences. You treat them differently-no cure but may be treatment. We need to run to catch up with science. We need more think tank type discussion. Anonymous | 02/24/2022 I am a 62 year old liver transplant recipient. Please consider expanding the definition of pediatric patients to include 13-17 year old patients. Region 8 | 02/23/2022 2 strongly support, 14 support, 2 neutral/abstain, 0 oppose, 0 strongly oppose - Region 8 supported this proposal. Several members asked the committee to revisit the terminology of birth sex and current sex. A member asked the committee to consider using the term "sex assigned at birth" rather than "birth sex" and inquired as to what will be done to improve equitable care to transgender patients. A member stated his support of removing gender disparity and noted that LSAM projections are not an exact prediction of lives saved based on previous projections. A member commented that patient and provider education should ensure transgender populations do not have disparity in access or receive unintentional biases. It was pointed out that there are more deceased donor livers being discarded and that we should figure out why. Region 4 | 02/18/2022 5 strongly support, 19 support, 2 neutral/abstain, 0 oppose, 0 strongly oppose - Region 4 supported the proposal. Two commenters were concerned that albumin could be manipulated and one went on to encourage the committee to speak to clinical pathologists to get their input about the variability in the test, results and ranges before moving forward. Another attendee commented that it is good to see the changes in PELD and commended the group on improving sorting for 1B to reflect the increased point requests. One attendee commented that this proposal is a thoughtful approach and equalization of gender transplant rates is a “win” Another attendee commented that is important to continue to refine definitions for high acuity patients. Region 5 | 02/16/2022 6 Strongly Support, 18 Support, 8 Neutral/Abstain, 1 Oppose, 0 Strongly Oppose - A member suggested to remove MELD of 25, minimum criteria for the listing at that status, since there are a lot of children that decompensate with GI bleeding that isn’t captured. A member supports the proposal but stated that he believes the sorting is random and that waitlist time doesn’t correlate with waitlist mortality well. The member supports making PELD exception points medium MELD time of transplant. He does not believe it is worthwhile to give points for waitlist. A member stated that they agree with the Status 1B sorting given current waitlist mortality risk. And that the committee could alternatively consider removing the children with metabolic disease from the Status 1B category and consider granting them median PELD at transplant with an opportunity to apply for additional exception points if a donor does not become available at the MPaT. A member pointed out that it will be important to follow the impact on waiting time for different subgroups, such as pediatrics with metabolic liver disease. A member stated that she was disappointed that the committee chose to only slightly change current MELD calculation and did not consider a larger change e.g. adding many more variables to come up with a more accurate predictor of waitlist mortality. For example, machine learning/AI derived formulae that accounts for changes in lab values over time and also at the same time stratifies HCC patients as well as fixes the gender/size disparity. Region 10 | 02/16/2022 4 Strongly Support, 8 Support, 2 Neutral/Abstain, 0 Oppose, 0 Strongly Oppose - The region supported the proposal but provided feedback for the committee to consider. In regards to the addition of albumin one member noted that albumin is modifiable in clinical settings and the committee should be cognizant of that as they finalize the proposal. Another member countered that it makes sense to include albumin since the data that was analyzed would account for albumin infusions in a clinical setting. Another member stated that using creatinine is a poor representation of kidney function, and the proposal should include the use of cystatin-c. Most transplant programs work in hospitals that are fairly savvy from the lab medicine perspective, and should be able to get cystatin-c. The OPTN does what is best for candidates and not what is convenient for the transplant hospitals, and measuring renal function with a more accurate way that will not discriminate against gender or race should be strongly considered. The member would support using cystatin c as the measure of kidney function in these candidates, both adult and pediatrics. Additionally, a member noted that the committee needs to create a meaningful definition for sex versus gender. This will provide clarity and transparency for centers since the proposal uses sex for calculations. Another member stated that they have had similar concerns at their program regarding Trans and non-binary patients, but they support the committee’s approach. Luke Preczewski | 02/08/2022 Any change to the MELD/PELD/S1A/S1B system needs to address the adverse impact the allocation system has on candidates in need of multivisceral transplantation. Rather than re-stating, I am attaching a letter (a letter substantially similar to this one was sent two years ago by the major MVT centers to the liver-intestine committee). If any proposal is moving forward to change the system, it should address this very small but very sick population who are disadvantaged under the current system. I appreciate the committee's attention to this. Attachment Anonymous | 02/03/2022 I do not support adding Sex and albumin, to MELD. Albumin again Definitely indicates severity of liver disease but also is subjective to confounding variables, albumin infusions and dietary patterns . Low albumin can also be secondary to protein losing enteropathy.