1. Changes to HCC Criteria for Auto Approval
Liver and Intestinal Organ Transplantation Committee

2. What problem will the proposal solve?
Current policy for automatic HCC MELD exception requests
Exception points for candidates that may do well without transplant
Exception points for candidates with poor post-transplantation outcomes
Certain HCC candidates currently excluded from automatic exception points
Implemented by the OPTN in 2002, the model for end-stage liver disease (MELD) allocation policy, provides “exception” scores for patients with hepatocellular carcinoma (HCC) that fall within T2 criteria, a definition of lesion size for automatic approval of exception requests. A candidate’s exception score should demonstrate how likely they are to drop off the waitlist because of HCC lesion progression. Candidates with a MELD score exception for HCC receive increased priority on the liver waiting list. Therefore, policy must appropriately balance prioritization between HCC candidates and non-HCC candidates, as well as prioritization among HCC candidates
Candidates that do well without transplant
Several studies have shown that a subset of HCC candidates that receive additional priority through the exception system have significantly lower dropout rates than non-HCC candidates . These candidates automatically receive exception points despite having a very low risk of disease progression or waiting list mortality.
Candidates with poor post-transplantation outcomes
The current policy for HCC exceptions does not adequately filter candidates who demonstrate HCC characteristics that indicate poor post-transplantation outcomes. Current policy excludes candidates outside the T2 definition of lesions from automatic exception points, however, there are a subset of HCC candidates within T2. These candidates have very high Alpha- Fetoprotein or AFP that exhibit characteristics suggesting a high probability of post-transplant recurrence and/or mortality.
Candidates currently excluded that benefit from transplant
Current policy does not describe eligibility criteria for candidates suitable for HCC downstaging through local-regional treatment. However, nearly all regions currently approve patients who present outside of T2 criteria and have undergone downstaging to within T2. This is leading to a high number of reviews for the review boards.

3. What are the proposed solutions?
Updated criteria for automatic approval of HCC exceptions
Single Small Lesions
Candidates with a single lesion between 2-3 cm must be treated with local-regional therapy to be eligible
If completely treated after 1 or more episodes of treatment  not eligible for automatic MELD exception, unless they demonstrate recurrent or new lesion(s)
Downstaging
Establishes criteria for candidates suitable for downstaging of lesions to within T2
High AFP Criteria
Candidates meeting T2 criteria but with an AFP > 1000 are not initially eligible
The proposed policy changes will modify the HCC exception criteria so that these candidates’ MELD scores will more accurately reflect their disease severity. It does this by focusing on three areas: Criteria regarding single, small lesions, the downstaging of lesions to within T2 criteria, and an AFP threshold for automatic approval.
HCC candidates with single, well-treated small lesions have been shown to have a low-risk of waitlist dropout due to disease progression or waitlist mortality . We propose the following policy changes:
Candidates who initially present with a single lesion between 2 and 3 cm must be treated with local-regional therapy in order to be eligible for automatic MELD exception
If the lesion is completely treated (defined as a Class 0 lesion) after 1 or more episodes of local-regional therapy, the candidate is not eligible for a standardized MELD exception until the lesion recurs or the candidate develops a new lesion.
If the lesion persists or recurs (define as Class 5 lesion) after 1 or more episodes of local-regional therapy, the candidate is eligible for a standardized MELD exception.
Successful downstaging of HCC to T2 criteria is associated with a low rate of HCC recurrence and excellent post-transplant survival, similar to those meeting T2 criteria without downstaging. The proposed addition to current policy describes the criteria that makes a candidate eligible for the downstaging protocol. Candidates meeting the criteria will be eligible for automatic priority following local-regional treatment, and if their residual lesions fall within T2 criteria. We propose the following policy changes:
Candidates that meet one of the following criteria are eligible for inclusion in a downstaging protocol:
One lesion greater than 5 cm and less than or equal to 8 cm
Two or three lesions each less than 5 cm and total diameter of all lesions less than or equal to 8 cm
Four or five lesions each less than 3 cm and total diameter of all lesions less than or equal to 8 cm
There is increasing evidence that clinical factors beyond lesion size and number are associated with a greater risk of HCC recurrence and poor post-transplant outcomes. The alpha-fetoprotein level or AFP is increasingly shown to predict poor outcomes post transplant. We propose the following policy changes:
Candidates with lesions meeting T2 criteria but with an AFP greater than 1000 are not eligible for a standardized MELD exception.
If these lesions fall below 500 after local-regional therapy, the candidate is eligible for a standardized MELD exception
Candidates with an AFP level greater than or equal to 500 at any time point following local-regional therapy will be referred to the review board

4. Supporting Evidence Single Small Lesions Downstaging
HCC candidates with single, completely treated small lesions have low-risk of waitlist dropout
Downstaging
Successful downstaging of HCC to T2 criteria associated with a low rate of HCC recurrence and excellent post-transplant survival
Similar to those meeting T2 criteria without downstaging
Regarding the evidence for criteria restricting single, well treated small lesions from automatic approval of MELD exceptions, numerous studies have shown these specific lesions to have a low-risk of waitlist dropout due to disease progression or waitlist mortality. For the purposes of this proposal, a single, small lesion is defined as 1 lesion between 2-3 cm, that has exhibited a complete response, which is defined as after receiving ablation, the tumor was less than 2 cm. Approximately 1,550 candidates were listed with an HCC exception that fit this criteria from This is over 10% of the HCC candidates added to the waiting list during this time.
We propose that those HCC candidates with a single lesion, 2-3 cm in size, that have been completely ablated, do not receive automatic priority. The candidate would be required to undergo local-regional therapy prior to their exception request, and if the lesion exhibits a complete response, or is completely treated after one or more episodes of local-regional therapy, the candidate would not be eligible for automatic priority. To address small lesions with a higher risk of disease progression, the proposed policy states that candidates would be eligible for automatic priority if the lesion persists after one or more episodes of local-regional therapy. We estimate that about 300 candidates added to the waiting list each year would not be granted automatic priority under this proposed policy. We propose that these candidates with small, well-treated lesions likely do not require a liver transplant, and thus do not require HCC MELD exception points.
In support of the proposed criteria for inclusion in a downstaging protocol, we reviewed current literature that shows successful downstaging of HCC to T2 criteria is associated with a low rate of HCC recurrence and excellent post-transplant survival. This is similar to those meeting T2 criteria without downstaging. We adopted the widely used UCSF downstaging criteria. Nearly all regions currently approve patients who present outside of T2 criteria and have undergone downstaging to within T2. The proposed downstaging criteria will provide a uniform policy to be used across regions.

5. Supporting Evidence High AFP Criteria
Increasing values of AFP, and an AFP exceeding 1000 ng/ml are associated with poor post-transplant outcomes and a predictor of HCC recurrence.
We reviewed the use of (AFP) level as a criteria for eliminating the automatic priority for HCC candidates who demonstrate a high risk of poor outcomes after liver transplant. The AFP level is increasingly shown to predict poor outcomes, and recognized as a predictive marker for HCC recurrence. We discussed our clinical experience to identify an AFP threshold for removing eligibility for an automatic approval of an HCC MELD exception.
Additionally, UNOS Research staff performed a retrospective analysis using a Cox regression model of post-transplant mortality, adjusted for laboratory MELD at transplant. These figures show the distribution of AFP and its relationship with post-transplant mortality. The analysis shows that declining AFP values are associated with better post-transplant outcomes, while increasing values are associated with an increased hazard of mortality. Recipients whose final AFP value prior to transplant exceeded 1000 ng/ml had a hazard ratio of 2.45 [95% CI: 1.83, 3.27] compared to recipients whose AFP values never exceeded 1000 ng/ml. An AFP greater than 1000 has been shown to be associated with poor post-transplant outcomes and a predictor of HCC recurrence. We discussed the merits of several AFP thresholds, but ultimately decided that an AFP level greater than 1000 should remove eligibility for automatic priority.

6. How will members implement this proposal?
Transplant Hospitals
Be aware of new criteria for automatic approval of HCC exception requests
Proposed policy will make existing information in the HCC Exception Request Form required
Indication that candidate has undergone local-regional treatment
Candidate’s AFP
Liver programs will need to be aware of the new criteria for automatic approval of HCC exception requests. To be eligible for an exception for HCC, members will be required to document new information in their candidates’ MELD/PELD Exception Score Request Form for the candidate’s initial request. Members will also need to document new information in their candidates’ MELD/PELD Exception Score Request Form to receive an extension on their HCC exception.
The proposed policy adds an additional requirement that programs indicate whether their candidate has undergone local-regional treatment when they initially assess that candidate before requesting a standardized HCC exception. However, this is already a required field in the MELD/PELD Exception Score Request Form. If a candidate has a single lesion between 2-3 cm, local-regional treatment will be required before automatic exception is granted. If ineligible for LRT, need to apply to RRB for exception rather than automatic exception.
Additionally, the proposed policy requires transplant centers to provide the candidate’s (AFP) level in the MELD/PELD Exception Score Request Form at the time they request an extension of the exception score. But this is already a required field in the MELD/PELD Exception Score Request Form.

7. How will the OPTN implement this proposal?
Expected Board Date of Dec. 2016
Large computer programming estimate
Communication and education effort to help members prepare
Depending on public comment received, we will present this proposal to the Board of Director in December If the board approves the proposal, implementation will require a significant level of preparation and effort. Due to the large programming effort, the new policy would not become effective right away if approved. Since the impact of these policy changes is significant, before the policy is implemented the OPTN will educate specific audiences about how to prepare and comply with the new policy and system changes. UNOS staff will work together to inform you when the educational resources are available and you should take advantage of these opportunities.

8. Questions? Ryutaro Hirose, MD Committee Chair Ryutaro.Hirose@ucsf.edu
Matt Prentice, MPH
Project Lead