1. Liver Transplantation and Organ Allocation in 2019
Julie Heimbach, MD
Professor and Chair, Division of Transplantation Surgery
Mayo Clinic, Rochester, MN
No disclosures

2. Objectives Pro/cons of the MELD allocation system
“Standard” versus “non-standard” MELD exceptions
Changing from a regional to a national review board
Changing from a DSA/Regional system to a broader circle based distribution system

3. Registered U.S. Patients Waiting for Transplants
Kidney
94,815
Liver
13,159
Heart
3,773
Lung
1,423
Kidney/Pancreas
1,629
Pancreas
816
Heart/Lung 46
Intestine
228
Total patients
113,740
8,250 (2018)
Source: 6/20/2019

4. US waiting list outcomes at 3 years: 2014-17
Kim et al AJT 2019
Approx 55% had LT, 20% removed for “too sick” and 13% died

5. Organ Allocation: the basics
Transplant is the standard for decompensated liver disease
Ideally, LT could be offered to every suitable recipient, when they needed it
Critical donor shortage, so there has to be a system
Ideal system: transparent, balancing medical urgency with post-transplant benefit

6. Predictive of 3-month mortality from liver disease
MELD System:
MELD Score = x Loge(creatinine mg/dL) x
Loge(bilirubin mg/dL) x Loge(INR)
Adopted 2002, C-statistic 0.83
MELDNa = MELD(i) *(137-Na) – [0.033*MELD(i)*(137-Na)]
Adopted 2016, C-statistic 0.87
Predictive of 3-month mortality from liver disease

7. Reduced waitlist mortality in MELD-Na era
Nagai et al Gastro 2018
90 day waitlist mortality 26% lower in MELD-Na era
No change in post transplant patient/graft survival at 1 year

8. Meld System: strengths
Liver allocation in the United States is currently based on medical urgency: “sickest first” (Final Rule, 1998).
The modified system MELD-Na accurately predicts wait-list mortality, and has reduced US wait-list mortality
Uses 4 common laboratory tests= relatively easy to update
“MELD Exceptions” were developed because certain complications of chronic liver disease, such as HCC or HPS have an increased risk of adverse outcome which is not reflected in laboratory based MELD score.

9. Standard Adult MELD Exceptions (US):
Hepatocellular carcinoma
HAT
Hepatopulmonary syndrome
Portopulmonary syndrome
Primary Hyperoxaluria
Familial amyloid polyneuropathy
Cystic fibrosis
Cholangiocarcinoma
Clinical personnel at transplant centers may now enter scores for their patients into UNetSM. UNetSM, however, cannot automatically review and approve these exceptions, so some sort of human review is still necessary.
OPTN/UNOS Board of Directors approved standardized criteria and MELD/PELD exception scores for patients for seven of the previous 17 diagnoses including: hepatopulmonary syndrome, cholangiocarcinoma, cystic fibrosis, familial smyloidosis, primary hyperoxalruia, and portopulmonary hypertension
The liver committee modified the RRB Guidelines to allow the RRB chairs to determine on their own if the standardized cases meet the criteria in policy, without forwarding it to the entire review board. RRB chairs will review the information that is submitted. If the case meets the stated criteria, the chair will mark it as approved. If not, UNOS staff will submit it to the entire review board.
To make it simpler to submit exception cases to the RRB chair, the liver committee developed standard templates for each of the diagnoses. Transplant centers should follow the directions provided and use the approved templates when they enter required information into the MELD/PELD exception application.
Once this additional information is submitted, the UNet system alerts UNOS RRB support staff.

10. Problems/ Pitfalls

11. “Non-standard” MELD exceptions:
Prior system in US: appeal to a regional board for cases not meeting policy-based exceptions.
Approximately 23% of approved exceptions are non-policy based (vs 67% for HCC and 10% for other standard diagnoses). Regional system inconsistent. Geographic disparity in access.
Current system in US (May, 2019): national liver review board, with guidance documents for approval, and fixed score based on median score for area of transplant (MMaT-3)

12. Adults with non-standard diagnoses: set to MMaT-3
May be suitable for exception
Budd Chiari (if TIPS not effective)
HEHE
Hydrothorax
HHT
Multiple Hepatic Adenomas
Neuroendocrine Tumors (NET)
Polycystic Liver Disease (PLD)
Primary Sclerosing Cholangitis (PSC)- with biliary sepsis
Small for Size Syndrome
Diffuse Ischemic Cholangiopathy
Late Vascular Complications- selected
Generally not suitable for exception
Ascites
GI Bleeding
Hepatic Encephalopathy
Pruritus
Chronic rejection

13. National Review Board: Structure
NLRB
Pediatrics
HCC
Other

14. Assigning Scores: Eliminating “MELD elevator” for standard exceptions
May have contributed to the MELD escalation at transplant
Waitlist mortality higher for non-exception
Non-exception candidates transplanted at higher MELD scores
Assign fixed score at 3 points below median MELD at transplant for the area of distribution
Overall, balances exception and non-exception patient access– concern for CCA
The Committee wants feedback from the community on the optimal method of assigning MELD score exception points. Currently, the MELD exception score for many standardized exception diagnoses begins at 22 points and automatically increases every three months to reflect a 10% increase in waitlist mortality, so long as the candidate continues to meet criteria in policy. This automatic three-month increase in standardized exception score is also referred to as the “MELD elevator.”
The MELD elevator is problematic for several reasons. The waitlist mortality for non-exception candidates actually exceeds the mortality for exception candidates. Non-exception candidates are also transplanted at higher MELD scores than those with approved exceptions. Some have suggested that the MELD elevator has contributed to the escalation in MELD score at transplant that has occurred over the past decade.
For candidates with certain standardized exception diagnoses, the Committee is considering whether it is appropriate to assign a fixed exception score that is 1 to 2 points below the median allocation MELD for the Donation Service Area (DSA) of the candidate’s transplant program. The Committee would recommend the same for non-standardized exceptions. The Committee also wants feedback from the community on whether to eliminate automatic increases in MELD score for the candidates upon extension.

15. There is significant geographic variation in access to LT
2010 SRTR data SRTR data
Kim et al AJT 2019

16. Attempted Liver distribution policy change:
Started working January 2013 : 3 national forums, 3 public comments cycles, modeled 150+ scenarios
Broader sharing policy passed board December 2017: shared for region plus 150 mile circle around donor hospital down MELD 32
Subsequent lawsuit May 2018 (continued use of DSA/region system not consistent with law)
Project Charge to Liver Committee June 25, 2018:
Do over-- Remove DSA & region from liver allocation by December 2018

17. Circle-based frameworks
Initial goal:
a population based circle
Acuity circles: large circle (500 nm) for status 1,
Small circle (150 nm) for MELD 37-40, medium circle 37-40, large circle 37-40
Small circle (150 nm) for MELD 33-36, medium circle 33-36, large circle 33-36
Small circle (150 nm) for MELD 29-32, medium circle for 29-32, large circle 29-32
Small circle (150 nm) for MELD 15-28, medium circle for 15-28, large circle 15-28
Only share for larger circle if no patient in smaller circle

18. 150 & 250NM

19. 500NM

20. Current 9.97 1.7 88.5 50.7 1455/.097 2017 Board Approved 7.41 100.4
Scenario
Variance in Median Allocation MELD/PELD
Median Transport Time (hours)
Median Transport Distance (miles)
Percent of Organs Flown
Waitlist Mortality Count/Rate
Current
9.97
1.7
88.5
50.7
1455/.097
2017 Board Approved
7.41
100.4
54.4
1386/.091
Acuity
4.33
1.9
183.5
71.4
1341/.087
Talk about how all four bring down the variance in MMaT. Acuity does it more, but B2C makes a difference too, and 32 does more than 35.

21. MEDIAN MELD/PELD at transplant by DSA
Middle two are AC, right 2 are B2C – 32 on the bottom. Talk about how they show an even-ing out of variance in Mmat – more so with AC, but still noticeably with B2C. This just shows it by DSA

22. Attempted Liver distribution policy change, cont:
Acuity circle passed board December, 2018
Anticipated Implementation April 30, 2019– another lawsuit
NLRB remains active, but broader sharing policy currently on hold.

23. Summary:
MELD allocation system prioritizes livers to the most urgent candidates
A system of exceptions is needed to account for complications of chronic liver disease that lead to an increased risk of death, that are not captured by MELD score– generally working, but switching to national rather than regional oversight board
Broader sharing to reduce geographic inequity: on-going
Change is difficult, and advocacy is an important part of the process