Donor Allocation Policy in the US W. Ray Kim Professor and Chief Gastroenterology and Hepatology Stanford University School of Medicine

Terminology Organ Distribution (Grouping) Geographic organization for organ sharing Consideration of logistics (i.e., cold ischemic time) Regions and Donor Service Areas Organ Allocation (Ordering) Determination of priority among transplant candidates Within/across distribution boundaries

Terminology Organ Distribution (Grouping) Geographic organization for organ sharing Consideration of logistics (i.e., cold ischemic time) Regions and Donor Service Areas Organ Allocation (Ordering) Determination of priority among transplant candidates Within/across distribution boundaries

Unit of Distribution for the severely ill 11 UNOS Regions Unit of Distribution for the severely ill

58 Donor Service Areas

Terminology Organ Distribution Geographic organization for organ sharing Consideration of logistics (i.e., cold ischemic time) Regions and Donor Service Areas Organ Allocation (Ordering) Determination of priority among transplant candidates Within/across distribution boundaries

Two cases Case #1 47-year old accountant with diabetes x 5 years Refractory ascites requiring TIPS procedure in 2015 Disabling encephalopathy, requires frequent hospitalization Lab: Bilirubin (3.0 mg/dl), INR (1.4), Creatinine (1.4 mg/dl) Case #2 69-year old grandmother of 5 with HCV (transfusion in the 1970s) Increasing ascites and encephalopathy Admitted with SBP Lab: Bilirubin (14.6 mg/dl), INR (1.8), Creatinine (1.9 mg/dl)

Who to Transplant? If there is one liver to transplant, to which of the two cases should it be given? 49-year old accountant with refractory encephalopathy MELD=18 9% 90-day mortality 97% expected 5-year survival with LTx 68-year old grandmother with SBP-induced hepatic decompensation MELD=29 35% 90-day mortality 82% expected 5-year survival with LTx To whom is LTx more life-saving? In whom will the LTx deliver more meaningful life?

Philosophy in Liver Allocation Use liver transplantation to save lives of dying patients Share donated livers to derive maximum benefit ‘Efficiency’ principle ‘Urgency’

Philosophy in Liver Allocation Sickest first Rescue from certain death in desperately ill patients Chance for post-LTx survival may be low. Maximize benefits of LTx Largest number of patients living with best quality of life Severely ill patients may not be offered Tx. ‘Efficiency’ principle ‘Urgency’

Regulatory Mandates Final rule (DHHS) on Organ Procurement and Transplantation Network (OPTN), 1998 Principles of organ allocation policies and procedures Allocate organs in the order of medical urgency Sound medical judgment Avoid futile transplantation Institute of Medicine (IOM) Report, 1999 Waiting time: not an appropriate measure of the fairness of the organ allocation system Equitable allocation of organs based on medical characteristics and disease prognosis 42 CFR Part 121: available http://optn.transplant.hrsa.gov/policiesAndBylaws/final_rule.asp

Better Off Without LTx? ‘Share 15 National’ Policy Tx Harmful Tx Better Merion Am J Transpl 2005;307

More Cases Case #3 53-year old musician with long history of drinking Ill with hepatic encephalopathy following a drinking binge Ascites, muscle emaciation, gynecomastia Lab: Bilirubin (14.6 mg/dl), INR (1.8), Creatinine (1.9 mg/dl) Case #4 19-year old college student with acute hepatitis A Encephalopathic Case #5 59-year old businessman with HBV cirrhosis and HCC Undetectable HBV DNA x 5 years on entecavir Ultrasound: 6-cm mass in seg 7 Lab: Bilirubin (3.0 mg/dl), INR (1.4), Creatinine (1.4 mg/dl)

Who to Transplant? If there is one liver to transplant, which patient should receive it? 49-year old accountant with refractory encephalopathy (MELD=18) 68-year old grandmother with HCV, hepatic decompensation, and SBP (MELD=29) 53-year old musician with alcoholic hepatitis (MELD=29) 19-year old college student with acute fulminant hepatitis A (MELD=29) 59-year old businessman with HBV and liver cancer (MELD=18) What if there were two livers?

History of Liver Allocation in the US 1980 1990 2000 2010 No Competition Allocation Increasing Demand Organ Shortage Liver transplant as an experimental, last resort procedure First-come-first-served Urgency status MELD Score Share 15 National Share 35 Regional MELD-Na 2002

Impact of MELD-based Allocation on Waitlist Outcome Decreased waitlist registration Drop in median waiting time Increased transplant rate Decrease in mortality Mortality per 100 patient-yeas

MELD Exception MELD score in HCC patients does not take into account adverse oncological outcomes in patients waiting for LTx. ESLD Patients Other ‘Exception’ Patients HPS, CF, PoPH, FAP, Oxaluria HCC Patients Tumor progression beyond the Milan criteria Disease progression to disqualify for LTx MELD score effectively captures risk of death from liver failure

MELD Exception for HCC Initial implementation (2002): MELD exception score = 29 2003 Revision: Exception = 24 2005 revision: Exception = 22 Upgrade scores: by 10% point increase in mortality every 3 months Time 3 6 9 12 15 18 21 Exception 22 25 28 29 31 34 36 39

Challenges to the MELD System HCC versus non-HCC Balance % Drop Out Days after registration Washburn. AJT 2010; 10: 1652–1657

MELD Exception for HCC Initial implementation (2002): MELD exception score = 29 2003 Revision: Exception = 24 2005 revision: Exception = 22 Upgrade scores: by 10% point increase in mortality every 3 months As of 2016, HCC exception MELD score has been capped at 34. Time 3 6 9 12 15 18 21 Exception 22 25 28 29 31 34 Time 3 6 9 12 15 18 21 Exception 22 25 28 29 31 34 36 39

Policing HCC Exception Policy Specification of imaging equipment/procedure Scanner, detector/coil type, contrast injection speed, etc. Specification of eligible imaging characteristics OPTN HCC Class (5A, 5B and 5T) Compliance monitoring Documentation of imaging records subject to audits by UNOS Submission of explant pathology form Within 60 days If no HCC in explant, must submit imaging report in support Committee review if >10% has no HCC on pathology report per year

UNOS HCC Imaging Criteria OPTN Class 5B: must meet all of the following Single nodule diameter 2-5cm Contrast enhancement in late hepatic arterial phase One of the following: Washout on portal venous/delayed phase, Late capsule or pseudocapsule enhancement, Growth by 50% or more documented on serial MRI or CT obtained < 6 month apart OR Biopsy OPTN Class 5A nodules: tumors 1-2 cm OPTN Class 5T nodules: OPTN Class 5B lesions treated loco-regionally.

Current Challenges Donor Shortage Scientific Registry of Transplant Recipients (SRTR: www.srtr.org)

Summary Tension between urgency and efficiency: Urgency first Avoid futile LTx Progresses: MELD improved waitlist outcome Exception scores Challenges: Donor shortage Better predictor of mortality (MELD-Na) Truly broader geographic sharing Equity among candidates with different indications

Current US Liver Allocation #3 49-year old accountant with refractory encephalopathy (MELD=18) 68-year old grandmother with SBP-induced hepatic decompensation (MELD=29) 53-year old musician with alcoholic hepatitis (MELD=29) 19-year old college student with acute fulminant hepatitis A (MELD=29) 59-year old businessman with HBV and liver cancer (MELD=18) #2 No #1 #3

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