current state of liver allocation and distribution john r. lake, md university of minnesota medical...
TRANSCRIPT
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