Liver and Intestinal Organ Transplantation Committee Report to the Board of Directors June 25-26, 2012 Richmond, VA Kim M. Olthoff, MD, Chair David C. Mulligan, MD, Vice-Chair

“Share 15 National” “Share 35 Regional” Endorsement of Liver Biopsy Resources (Consent Agenda) Items Submitted for Board Consideration

Despite improvements in liver allocation and distribution, waitlist mortality remains high for patients with higher MELD scores Significant disparity exists between OPOs and regions with regard to mean MELD at transplant and waitlist mortality How can we direct livers to most in need? Problem Statement

Supporting Data

Competing Risk Liver Waiting List Outcome Probabilities at 1-Year Candidates Added *Status 1A/1B, and candidates with exceptions excluded N=10319 N=15810N=2363

Mean Match Transplant* Deceased Donor Liver Transplants, 2010 by DSA within Region *Adults only, Exceptions. Some DSAs may overlap

Death 365 Days, Candidates Listed for a DD Liver Transplant 1/1/ /31/09 By DSA within Region *Adults only, Calculated using Competing Risks, Exceptions, Initial MELD>=15, Candidates with an Initial Status of 1A/1B Excluded, DSAs with fewer than 10 events excluded

Results: Waitlist Mortality – Intent to treat

Results: Waitlist Mortality – As treated Status 1A MELD/PELD % Temporarily inactive 22% changed to MELD 53% Temporarily inactive 6.5% changed to 1A/1B 40.5% changed to lower MELD

Post Transplant Patient Survival – KM Curve

Policy Development

Proposal for Regional Sharing (February 2009) Request for Forum (June 2009) RFI and Survey (December 2009) Forum in Atlanta (April 2010) Board directed Committee “to develop recommendations to reduce geographic disparities in waitlist mortality” (June 2010) Concept Paper/Survey (December 2010) Policy Development History I

Presentations at AASLD, ASTS Winter Symposium, ATC (2010 and 2011) Public Comment (September - December 2011) Public Webinar (October 2011) Review of Comments (March 2012) Final Committee Vote (May 2012) Policy Development History II

Full Regional Sharing – strong opposition Concentric Circles – mixed support Extension of Share 15 Regional – strong support Tiered Regional Sharing – strong support for some level (29, 32, 35, other) Net Transplant Benefit – mixed support Options Considered

Extension of Regional Share 15 => Share 15 National Share 35 Regional - Candidates with MELD/PELD scores of 35 and higher Could be combined if both approved Policy Changes Being Proposed

1.Combined OPO and Regional LI Status 1A 2.Combined OPO and Regional LI Status 1B 3.OPO LI MELD/PELD ≥ 15 4.Regional LI MELD/PELD ≥ 15 5.OPO LI MELD/PELD < 15 6.Regional LI MELD/PELD < 15 7.National LI Status 1A 8.National LI Status 1B 9.National LI MELD/PELD. i.e.,: National LI MELD/PELD >=15 National LI MELD/PELD <15 Current Algorithm* *Does not include recently-approved liver-intestine policy

1.Regional Status 1A 2.Regional Status 1B 3.Local MELD/PELD>=15 4.Regional MELD/PELD>=15 5.National Status 1A 6.National Status 1B 7.National MELD/PELD>=15 8.Local MELD/PELD<15 9.Regional MELD/PELD<15 10.National MELD/PELD<15 Share 15 National* * Adult Donors Only

1. Regional Status 1A 2. Regional Status 1B 3. Local and Regional M/P >=35 4. Local M/P Regional M/P Local M/P < Regional M/P <15 8. National Status 1A 9. National Status 1B 10. National M/P ≥ National M/P < 15 Share 35 Regional * 3.1 Local M/P Regional Local M/P Regional M/P Local M/P Regional M/P Local M/P Regional M/P Local M/P Regional M/P Local M/P Regional M/P 35 * Adult Donors Only

1. Regional Status 1A 2. Regional Status 1B 3. Local and Regional M/P >=35 4. Local M/P Regional M/P National Status 1A 7. National Status 1B 8. National M/P ≥ Local M/P < Regional M/P < National M/P < 15 Share 35R, Combined with Share 15N* 3.1 Local M/P Regional Local M/P Regional M/P Local M/P Regional M/P Local M/P Regional M/P Local M/P Regional M/P Local M/P Regional M/P 35 * Adult Donors Only

Potential Impact LSAM MODELING REDUCTION IN WAITING LIST DEATHS PER YEAR

Post-Public Comment Consideration

Type of Response Response Total In Favor In Favor as Amended Opposed No Vote/ No Comment / Did not Consider Individual42 28 (75.7%) 0 9 (24.3%) 5 Regional11 11 (100%) 000 Committee19 4 (100%) 0015* Public Comments – Share 15 *Ethics and MAC commented but did not vote Percentages based on responses with an opinion

Committees in Support: Patient Affairs, Pediatric Transplantation, Transplant Administrators and Transplant Coordinators Societies in Support: AST, ASTS, NATCO Opposition: increased costs/CIT; threshold of 15 being based on old analyses; patients with congenital hepatic fibrosis Public Comments – Share 15

Hypothesis: Greater access to organs for sicker candidates will decrease their waiting list mortality, without a demonstrable increase in mortality for other candidates, due to the small number of candidates involved. Data to be reviewed every 6 months post-implementation: Waiting list mortality by MELD score Post-transplant patient and graft survival Percent shared between OPOs Percent shared nationally Plan for Evaluating the Proposal

This proposal does not require additional data collection in UNet℠. Data Collection

*** RESOLVED, that modifications to Policy 3.6 (Allocation of Livers, Adult Donor Liver Allocation Algorithm) are hereby approved as set forth in Resolution 18, effective pending programming in UNet℠ and notice to OPTN membership. Resolution/Policy Language

Type of Response Response Total In Favor In Favor as Amended Opposed No Vote/ No Comment / Did not Consider Individual44 26 (66.7%) 13 (33.3%) 5 Regional11 5 (45.4%) 3 (27.3%) 3 (27.3%) (1 tie vote) 0 Committee19 4 (100%) 015* Public Comments – Share 35 *The MAC commented without voting Percentages based on responses with an opinion

Region Approved as Written* Approved as Amended* General Comments Costs, CIT, post-txp survival Consider sharing threshold AAS for Hawaii Share for SLK (with payback) pt sharing threshold Regional Votes – Share 35 * Votes: Yes - No - Abstention

Committees in Support: Patient Affairs, Pediatric Transplantation, Transplant Administrators and Transplant Coordinators Societies in Support: AST, ASTS, NATCO Opposition: increased costs/CIT; potential effect on small programs; inclusion of exceptions and candidates awaiting a combined liver-kidney transplant; and use of a “sharing threshold.” For each option, some comments and regions were in support (e.g., exceptions must be included) while others were in opposition (e.g., exceptions must be excluded). Public Comments – Share 35

Sharing threshold Very complicated in concept and would be in practice LSAM modeling – affected only 5% of transplants (ranging from 4.68% to 5.16% across the proposals modeled) CIT SRTR analyses showed that CIT does not correlate well with distance, ranging from 6 hours for very short distances, to 7 hours for distances of 250 miles or more. This may be more related to center practices for transplantation of local versus imported donors. Response to Public Comment - I

Variance for Hawaii HI may submit a variance application Inclusion or Exclusion of Exceptions See additional data ⁻ HAT ⁻ HCC ⁻ Others Inclusion of SLK See additional data Response to Public Comment - II

Additional Data Requested to Assess Inclusion of Exceptions and SLKs

MELD/PELD 35+ Candidates 2009 – 2011: By Region Candidates Reaching M/P 35+ All NoYes N%N%N Region All The percentage of all candidates listed who entered MP35+ ranged by region from 6.4% to 14.9%. Regions 2,5 and 7 had the largest numbers.

MELD/PELD 35+ Candidates 2009 –2011: Categories of Exceptions and Standard Cases MP35 CategoryN% HAT Exception HCC Exception Liver-Intestine Other Exception Standard MELD/CRRT (HD 2x in week) Standard MELD/no CRRT Total About 90% of the candidates in MP35+ were assigned standard MELD/PELD scores; less than 1% were HCC exceptions.

MELD/PELD 35+ Candidates 2009 –2011: Rates of Death* and Transplant By Kidney Listing/Dialysis *Includes candidates removed for too sick Being either on the KI WL or on dialysis was associated with higher death rates and lower transplant rates. Candidates on KI WL and on dialysis (N=430) had highest death rates at 90 days (39.1%) and lowest transplant rate (49.8%) (data not shown).

MELD/PELD 35+ DD Txs 2009 –2011: 1 Yr Graft/Patient Survival Rates by Type of Exception and Standard MELD/PELD Category Note: All Exceptions vs. All Non-Exceptions (Graft: 86.7% vs. 78.4% Patient: 90.0% vs. 81.2%) Standard MELD recipients on dialysis had the lowest survival at 1 year; Non-HAT exceptions had the highest 1-year survival.

MELD/PELD 35+ DD Txs, 2009 –2011: 1-Yr Graft/Patient Survival Rates by Dialysis Status, Kidney Listing, and Kidney Transplant Recipients on dialysis had lower graft and patient survival rates; Recipients listed for a KI that did not receive a KI transplant with the liver had the lowest survival rates (at 10 months).

No Sharing Threshold: Committee Vote 20 in favor, 2 opposed, and 1 abstention Include All Exceptions: Committee Vote 20 in favor, 2 opposed, and 1 abstention Include Candidates in need of Combined LI-KI: Committee Vote 27 in favor, 1 opposed and 0 abstentions Submit Share 35 to the Board: 27 in favor, 1 opposed, and 0 abstentions Final Proposal

Hypothesis: Greater access to organs for sicker candidates will decrease their waiting list mortality, without a demonstrable increase in mortality for other candidates, due to the small number of candidates involved. Data to be reviewed every 6 months post-implementation: Waiting list mortality by MELD score Post-transplant patient and graft survival Percent shared between OPOs Percent shared nationally Percent of MELD exceptions scores transplanted at high MELDs (35+) Plan for Evaluating the Proposal

This proposal does not require additional data collection in UNet℠. Data Collection

*** RESOLVED, that modifications to Policy 3.6 (Allocation of Livers, Adult Donor Liver Allocation Algorithm) are hereby approved as set forth in Resolution 19, effective pending programming in UNet℠ and notice to OPTN membership Resolution/Policy Language

BIOPSY RESOURCES

Organ Availability Committee (OAC) developed a standardized liver biopsy reporting form and accompanying resource document – Committee Dissolved in 2011 Purpose: to improve the accuracy and completeness of the information surgeons need when considering a liver for their patients. Designed for OPOs to make available to their pathologists. Not mandatory, forms; would be provided by OPOs as a resource. Photo resource document: standardized photographs in situ and on the back-bench to assist in decision-making regarding organ suitability by augmenting (but not replacing) clinical judgment and/or biopsy results. Will be helpful when the procuring team is not the transplanting team. Biopsy Resources

Photo Documentation Resource Guide

*** RESOLVED, that the Liver Biopsy Form and Resource Documents developed by the Organ Availability Committee and set forth in Exhibit H to the Liver and Intestinal Organ Committee‘s report to the Board, are hereby approved and effective pending notice to OPTN membership. Resolution