CURRENT STATE OF LIVER

ALLOCATION AND

DISTRIBUTION

John R. Lake, MDUniversity of Minnesota Medical School

Outline

• Initiation of MELD Allocation• Unintended consequences of MELD

allocation• Status 1 regional sharing• Share 15 rule• MELD exceptions• Current Status

INITIATION OF MELD ALLOCATION IN THE US

MELD EQUATION

• MELD =(0.957 x LN(creatinine) + 0.378 x LN(bilirubin) +1.12 x LN(INR) +0.643) x 10

• Capped at 40

Comparison of Two Eras and the Impact of MELD/PELD

Era 1(2/28/01 - 8/28/01)

Era 2(2/28/02 - 8/28/02)

New listings

Cadaver transplant

Living donor transplant

Mean MELD at transplant

Retransplant

HCC

Liver/kidney

5697

2358

250

11.4

86

8.8%

1.1%

4746

2478

187

22.1

81

21.7%

2.1%

p<0.01

p<0.01

p ns

p<0.01

p ns

Source: Draft 2006 OPTN/SRTR Annual Report, Tables 1.7 and 1.8.

Recipients of Liver Transplants and Simultaneous Liver-Kidney Transplants by Year

1996-2005

0

1000

2000

3000

4000

5000

6000

7000

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

0.00%

1.00%

2.00%

3.00%

4.00%

5.00%

6.00%

Liver (DD, LD) Liver-kidney % Liver-kidney

Total Number of Waitlist Registrants

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

1985 1990 1995 2000 2005

MELD

9,090 9,349

0

2,000

4,000

6,000

8,000

10,000

12,000

14,000

16,000

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

Year

Source: Draft 2006 OPTN/SRTR Annual Report, Table 9.1a.

Number of Patients on the Liver Waiting List Active at Year-End 1996-2005

Num

ber

of P

atie

nts

on W

aitin

g Li

st

0

20

40

60

80

100

120

140

160

180

200

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

Year

De

ath

ra

te p

er

10

00

pa

tie

nt

ye

ars

at

risk

Source: Draft 2006 OPTN/SRTR Annual Report, Table 9.3.

Unadjusted Death Rates per 1,000 Patient Years at Risk for Patients on the Liver Waiting List

1996-2005

0

100

200

300

400

500

600

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

Year

Nu

mb

er

Liv

ing

Do

no

r R

ecip

ien

ts

Number of Living Donor Liver Recipients 1996-2005

Source: Draft 2006 OPTN/SRTR Annual Report, Table 9.4b.

Mean MELD Scores

0

5

10

15

20

25

30

35

1 2 3 4 5 6 7 8 9 10 11

UNOS Regions

mea

n M

EL

D S

core

Non-exception Exception Transplant MELD

WAITING TIME > 90 DAYSBy Region

0

10

20

30

40

50

60

70

80

1 2 3 4 5 6 7 8 9 10 11

% WT > 90 DAYS

UNINTENDED CONSEQUENCES OF MELD ALLOCATION

SLK TRANSPLANTS OVER TIME

0

50

100

150

200

250

300

350

400

450

1999 2001 2003 2005 2007

# OF SLK TX

Current State of Liver/Kidney Transplants in the U.S.

Transplant Group

Frequency Percentage

LTA no HD 11.055 89.9

LTA with HD 556 4.5

SLK no HD 277 2.3

SLK with HD 406 3.3

Total 12,294 100.0

SRTR 2005 Report: Txs from 2/27/02-6/30/05

Hepatocellular Cancer MELD Prioritization

Centers recertify every 3 months. Patients continuing to meet stage I or II definition receive additional 10% mortality risk points (~3-4 MELD points)

Original April 2003 Current

Stage I1 tumor < 2cm

15% Risk =MELD 24

8% Risk =MELD 20

0 Risk =MELD calculated

Stage II1 tumor 2 cm but < 5 cm or 2-3 tumors largest < 3 cm

30% Risk =MELD 29

15%Risk =MELD 24

15% Risk =MELD 22

Transplants for HCC

0

100

200

300

400

500

600

# T

ran

spla

nts

HCC2/27/01-02 2/27/02-03

0

100

200

300

400

500

600

700

800

900

6 9 12 15 18 21 24 27 30 33 36 39

Adult Liver Transplants February 28, 2002 - February 28, 2003

MELD Score

Status 1

Hepatocellular CA MELD Prioritization

Centers recertify every 3 months. Patients continuing to meet stage I or II definition receive additional 10% mortality risk points (~3-4 MELD points)

Original April 2003 Current

Stage I1 tumor < 2cm

15% Risk =MELD 24

8% Risk =MELD 20

0 Risk =MELD calculated

Stage II1 tumor 2 cm but < 5 cm or 2-3 tumors largest < 3 cm

30% Risk =MELD 29

15% Risk =MELD 24

15% Risk =MELD 22

STATUS 1 SHARING

STATUS 1 SHARING• In 1999, patients listed as status 1, were listed

at the top of the list, and the unit of distribution was changed to the region

• Status 1 patients included:• Acute liver failure (duration, less than 6 weeks)• Primary nonfunction or hepatic artery thrombosis

within 1 week of a transplant• Critically ill pediatric patients

• Patients had to be in the ICU with a life expectancy of < 7 days

Causes of Liver Failure in 2 Groups (Before and After the August 21, 1999, Adoption of Region 7 Sharing

for Status 1 Patients) U of Minnesota

Cause of Listing for status 1

Group 1Before sharing

Group 2After sharing

FHF 13 14

Pediatric ICU 1 2

PNF 3 0

HAT 2 4

Total 19 20

Waiting List and Post-transplant Outcomes Pre- and Post-Sharing

Group 1 (Before Sharing) n = 19

Group 2 (After Sharing) n = 20

P Value

Waiting list (WL) mortality

6 (32%) 1 (5%) 0.03

Mean days on WL (all)

5.8 2.9 0.04

Mean days on WL (Tx only)

5.6 3 -

Mean days on WL (patients

dying)

6.5 1 0.02

Patient survival (6 months)

69.2% 89.5% 0.03

Graft survival (6 months)

69.2% 89.5% 0.03

STATUS 1 SHARING: Problems

• Status 1 patients included:• Acute liver failure (duration, less than 6 weeks)

• Wait list mortality still too high

• Primary nonfunction or hepatic artery thrombosis within 1 week of a transplant

• No strict definition of PNF and almost no one listed status 1 for HAT died

• Critically ill pediatric patients• 1/2 of transplants in pediatric patients were at status 1

Log (RR) of Waitlist Death by MELD Score Patients Added to the List 2/27/02-2/26/03

-1

0

1

2

3

4

5

6

6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40

Lab MELD

Log(RR)

*Censored at earliest of transplant, removal from the waitlist for reason of improved condition, next transplant, day 60 at status 1 or end of study; unadjusted; includes exception score patients (HCC 24 and 29 rules); follow-up through 9/30/03

Status1: Fulminant

Status1: PNF/HAT

HCC

Other

STATUS 1 SHARING: Problems

• Status 1 patients included:• Acute liver failure (duration, less than 6 weeks)

• Wait list mortality still too high

• Primary nonfunction or hepatic artery thrombosis within 1 week of a transplant

• No strict definition of PNF and almost no one listed status 1 for HAT died

• Critically ill pediatric patients• 1/2 of transplants in pediatric patients were at status 1

Time at Risk and Events for PELD Waitlist Mortality Analysis

(2/27/02-6/30/03)

Status 1: Fulminant 23 3,565 18Status 1: PNF/HAT 25 397 9Status 1: Chronic 22 2,625 0Exceptions 12 13,527 13

Median Lab PELD

Total patient days at score Deaths

* follow-up through 9/30/03

STATUS 1 SHARING: Changes

• Status 1 divide into 1a and 1b; with 1 a patients being those with acute liver failure or PNF or HAT with evidence of marked liver injury and dysfunction

• Status 1 patients included only pediatric patients with very severe chronic liver disease, metabolic diseases or hepatoblastoma

• Patients still have to be in the ICU with a life expectancy of < 7 days

Deceased Donor Transplants by MELD/PELD Allocation vs Other

68 69 69 71 69

9.6 9.2 9.0 7.0

14.7 14.4 13.5 14.7 15.6

7.3 7.9 8.4 8.0 8.5

6.7

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

2003 2004 2005 2006 2007

Year

% D

D T

ran

sp

lan

ts

MELD/PELD Status 1 HCC Except Other Except

SHARE 15 RULE

% MELD < 10 at Deceased Donor Transplant (2/27/02-10/31/04)

0%

10%

20%

OPO

% M

EL

D<

10

Adults only; Status 1 and exception patients excluded

OPOs with no transplants below MELD=10

SRTR

SHARE 15

On 1/12/05, the liver allocation system changed:Local – Status 1A, Status 1BRegional – Status 1A, Status 1BLocal – MELD/PELD > 15Regional – MELD/PELD > 15Local – MELD/PELD < 15Regional – MELD/PELD < 15National – Status 1A, Status 1B, MELD/PELD

Previously:Local – Status 1A, Status 1BRegional – Status 1A, Status 1BLocal – MELD/PELDRegional – MELD/PELD National – Status 1A, Status 1B, MELD/PELD

Percent of Transplant Recipients with MELD/PELD 15 by DSA

50%

60%

70%

80%

90%

100%

1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49DSA

% M

EL

D/P

EL

D >

15

Post-Share15

Pre-Share15

Transplants by MELD/PELD Score

0%

5%

10%

15%

20%

25%

30%

35%

40%

<=6 7-10 11-15 16-20 21-25 26-30 31-35 >35

Pre-Share15 Post-Share15

2147 2084

504 524

0

500

1000

1500

2000

2500

3000

After TPx

Before TPx

After TPx 504 524

Before TPx 2147 2084

Current 15 Point Rule

Effect of 15 Point Rule on Mortality

26,897 waitlisted candidates, 5,528 deceased donors

LSAM modeling

Reason for Removal from the Liver Wait ListAmong Candidates with MELD/PELD at Removal ≥ 15

Removal Date During Pre- or Post-Period

0.5 4.5

77.8

11.7

0.4 3.3 2.4 4.52.13.0

81.5

8.5

0

10

20

30

40

50

60

70

80

90

TXP - DD Died Recovered Too sick TXP - LD Other

Reason for Removal

% o

f re

mo

vals

Pre-Share15Post-Share15

MELD EXCEPTIONS

CRITERIA BY WHICH ADDITIONAL POINTS SHOULD BE AWARDED

Increased mortality risk: Points should not be given for “quality-of-life” indications

Clear diagnosis: It must be documented that patient meets established diagnostic criteria

Evidence based: Assigned MELD score should reflect mortality risk based on established disease natural history

Open to reassessment: Waiting list mortality for such patients should be periodically assessed

MESSAGE Meeting: MELD Exception Study Group

March 2, 2006

R.Gish, R. Wiesner and J. Lake

Liver Transplantation 12 (S3), S85-136, 2006

Deceased Donor Transplants by MELD/PELD Allocation vs Other

68 69 69 71 69

9.6 9.2 9.0 7.0

14.7 14.4 13.5 14.7 15.6

7.3 7.9 8.4 8.0 8.5

6.7

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

2003 2004 2005 2006 2007

Year

% D

D T

ran

sp

lan

ts

MELD/PELD Status 1 HCC Except Other Except

Percent of Adult Candidates Who Died Prior to Transplant by Waiting List Status on January 1, 2007

by MELD and Exception

0.2 0.2 0.5

3.1

14.8

0.5 0.90.5

5.9

14.8

1.1 1.80.9 1.2

3.2

7.1

14.8

1.1 1.81.9

2.1

0

5

10

15

20

<11 11-14 15-20 21-30 >30 HCCExcept

OtherExcept

MELD vs Exception Category

Can

did

ates

(%

)

30 days 60 days 90 days

Annual Waiting List Death Rates by MELD and Exception Categories

0

100

200

300

400

500

600

700

800

2002 2003 2004 2005 2006 2007Dea

th r

ated

per

100

0 p

atie

nt

year

s

MELD 11-14 MELD 15-20 MELD 21-30 HCC Other Exceptions

MELD EXCEPTIONS OVER TIME

0

100

200

300

400

500

600

700

800

900

2002 2003 2004 2005 2006 2007 2008

Number ofexceptions

MELD EXCEPTIONS OVER TIMEOther HCC

0

5

10

15

20

25

2002 2003 2004 2005 2006 2007 2008

% Other HCC

% OF EXCEPTIONS OTHER HCC BY REGION

0

5

10

15

20

25

30

35

40

1 2 3 4 5 6 7 8 9 10 11

% Other HCC

SUMMARY• MELD has stood the test of time as an

excellent allocation tool in a “sickest-first” model

• Distribution accounts for the variation in transplant rates by DSA and needs addressing

• We must develop better models to address recipients receiving MELD exception points

• Allocation of kidneys to those with AKI and CKD in the setting of chronic liver disease remains imperfect