Use of Extended Criteria Donor Organs

for Liver Transplantation

Antalya, Turkey
September 4, 2007

Charles B. Rosen, MD
Surgical Director, Liver Transplantation
Mayo Clinic Rochester
Mayo Clinic College of Medicine
Use of Extended Criteria Donor Organs for
Liver Transplantation

Liver Transplantation Strategy

Results with Liver Transplantation
Millenium Challenges
(Performance, Allocation, ECD and DCD)
Organ Transplantation Breakthrough
Collaborative
Liver Transplantation
Aims

• Prolong life
• Improve quality of life

For patients with acute

or chronic end-stage
liver disease
 Liver Transplantation
Indications

• Ascites, SBP • Growth failure

• Variceal hemorrhage • Fatigue and weakness
• Encephalopathy • Hepatocellular carcinoma
• Pruritus • Hilar cholangiocarcinoma
• Hepatorenal syndrome • Metabolic disease
• Muscle wasting • Acute liver failure
 Liver Transplantation
Patient Selection - Predictors of Success
• Technical difficulty
– Prior abdominal operations
– Portal vein thrombosis
• Severity of liver disease
• Other medical issues
– Heart, lung, and kidney problems,
diabetes
• Psychosocial status
– Compliance
– Chemical dependency
 Mayo Clinic Rochester
Liver Transplant Program
1985 - 2007

*1773 transplants
* 1591 primary transplants
*70 living donor transplants
*1138 living patients
Waiting list 389 patients
80-109 transplants per year since mid 1990’s
**91% patient and 88% graft survival at 1 year
**84% patient and 79% graft survival at 3 years
*August 30, 2007
**www.ustransplant.org (Tables 10 and 11)
Mayo Clinic Rochester Liver Transplant Program
Adult Patient Survival - Primary Transplantation
n = 1442
100
90
80
70
60
50
40
1985 - 2006
30
20
10
0
0 1 2 3 4 5
Mayo Clinic Rochester Liver Transplant Program
Adult Patient Survival - Primary Transplantation
100 92%
90 83%
80
70
60
50 1985-1990, n=227

40 1991-1995, n=335

30 1996-2000, n=408

20 2001-2005, n=407
10
0
0 1 2 3 4 5
SUCCESS AT THE MAYO CLINIC
– A BIRD’S EYE VIEW
 Liver Transplant Program
Adult Patient Survival

100
90
1985-1990
80
1991-1995
70
1996-2000
60
50 2001-2005
40
30
20
10
0
1 Year 3 Year
 Liver Transplant Program
Millennium Challenges
• Increase in waiting list
– Deaths
– Morbidity

• MELD/PELD liver allocation

• Changes in organ donation
– Increase in donor age
– Increase in medical vs trauma deaths

• Increasing competition
– Patients
– Donor organs
 Liver Transplant Program
Millennium Strategy
• Increase use of extended criteria
donor organs
– Marginal organs
– Higher risk donors
• Living donor liver transplantation
• Waiting list management
• Accommodate the “cluster effect”
 Liver Transplant Program
Older Donors

• Mayo Clinic Rochester 1998 - 2002

• 25 donors age 70-80 years
• 95% one-year patient survival
• 1 retransplant for “small-for-size” graft
– Avoid small grafts in large patients
• High risk for recurrent HCV
– Avoid older donor livers for HCV patients

Transpl Int 2005; 18:73

 Liver Transplant Program
Older Donors

• Result of aim to use all transplantable

livers from older donors:
–Donors > 65 years: 15% of activity
–Donors > 70 years: 10% of activity
–Actual patient survival remains high
–Decrease in expected patient survival
 Liver Transplant Program
Waiting List Management
• Maximize each and every patient’s
opportunity to receive a deceased donor
liver
• Donor organ acceptance decisions guided
only by each patient’s best interest in
order on the waiting list
• Identify “disadvantaged” patients whom
would benefit from transplantation with an
extended criteria donor liver
 Deceased Donor Liver Allocation
February 2002 Changes

OLD UNOS POLICY NEW UNOS POLICY

• Local, regional, national • Local, regional, national

• Medical status →→ • Probability of death
• Waiting time →→ • No waiting time
• Regional sharing for • Regional sharing for
status 1 status 1
• Status 2A for ICU → → • No preference for ICU
patients patients
 Deceased Donor Liver Allocation
February 2002 Changes

OLD UNOS POLICY NEW UNOS POLICY

Medical Status Probability of Death
Waiting Time No Waiting Time

Child-Turcotte-Pugh Score →→ MELD Score

• Ascites • Creatinine
• Encephalopathy • Protime INR
• Bilirubin • Bilirubin
• Protime INR
• Albumin
 Deceased Donor Liver Allocation
Patients Awaiting Transplantation
ADVANTAGED DISADVANTAGED
• High MELD score • Debilitating illness with
• Renal failure, low MELD score: ascites,
anticoagulation encephalopathy, pruritus
• Hepatocellular carcinoma • Cholestatic liver diseases,
chronic graft failure
• Special diseases:
amyloidosis, oxalosis • Special conditions: PPH,
logistics, foreign national
• Special conditions: HPS patients
• ABO: AB • Emerging indications:
CCA, NET
 Deceased Donor Liver Allocation
Patient Waiting List Management

• Coordinator responsibilities:
– Arrange tests for score renewal and updates
– Notification for patients nearing time of
transplantation
– Ongoing clinical care coordination
• Identification of disadvantaged patients
– Living donor transplantation
– Expanded criteria donor organs
• Weekly list review
• Database
 Liver Transplantation
Expanded Donor Criteria

High Risk Donors Marginal Organs

• HCV Ab+
• HBcAb+
• Intracranial malignancies
• Remote malignancies
• High risk behavior/exposure
• Infectious cause of death
(HSV, meningitis)
• Older donors (malignancies)
• Familial amyloidosis
• Steatosis
• Ischemia
• Elevated enzymes
• High serum sodium
• High pressor requirement
• Active infection, sepsis
• Prolonged preservation time
• Split liver grafts
• Donation after Cardiac Death
(DCD)
 Liver Transplant Program
Accommodating the Cluster Effect

• Cluster effect: two or more transplants

occurring during the same day
• 43% of transplants for a program
performing 100 deceased donor transplants
per year
• Opportunity cost of limited staffing:
– 2 transplants per day limit: 10-15
– 1 transplant per day limit: 20-25
 Liver Transplant Program
2001 - 2005 Strategy Summary

• Use of extended criteria donor

organs
• Living donor liver transplantation
• Waiting list management
• Accommodate the “cluster effect”
 Liver Transplant Program
2001 – 2005 Results Summary

• Maintained high level of activity

• Maintained high patient survival
• Achieved statistically higher than
expected patient and graft survival
 Liver Transplant Program
Transplant Activity
120

100

80

60

40

20

0
1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005
 US Center-Specific Data
Adult Patient Survival – July 2007

100
90
80 90.8 Observed
86.3 83.5
70 79.0 Expected
60
50
40
30
20
10
0
1 Year 3 Year

* Statistically higher than expected patient survival at 1 year

www.ustransplant.org
 US Center-Specific Data
Adult Patient Graft Survival – July 2007

100
90
80 88.5 Observed
83.6
70 79.3
73.5 Expected
60
50
40
30
20
10
0
1 Year 3 Year

* Statistically higher than expected graft survival at both 1and 3 years

www.ustransplant.org
 Liver Transplant Program
Strategic Results
• Mayo Clinic identification as a
“center of excellence”
• Attracts patients
• Lower cost of transplantation
• More transplants with higher
survival benefit helps more patients
 Organ Donation Awareness

• Hospital development
• Donor designation legislation
• National priority
• HRSA National Collaboratives
–Organ Donation: 75% donation rate
–Organ Transplantation : 3.75 organs
per donor
HRSA Organ and Donation Transplantation
Collaboratives
Government at its best

• HRSA – study best practices

– Donor hospitals
– Organ procurement organizations
– Transplant centers
• Faculty – develop “change package”
• Learning congresses – widespread sharing and
collaboration
• Result – rapid implementation, breakthrough
changes, dramatic results
 The Possibility – to Double Annual
Transplants

Donors/year
50% 6,000 75% 9,000

Recipients/year
3/D 18,000 4/D 36,000
 Number of Organ Donors by Month
750 Transplant Collaborative
2nd Donation Collaborative
Number of organ donors

700
1st Donation Collaborative

650
Old System

600

550

500

450
New System
400
10

10

10

10

10

10

10
1
4
7

1
4
7

1
4
7

1
4
7

1
4
7

1
4
7

1
4
7

1
4
1999 2000 2001 2002 2003 2004 2005 2006

Month
We have a lot more donors
and organs than we used to
have…
…and a lot less sleep as well!

- notorious transplant surgeon

 Donation After Cardiac Death
• The norm for organ procurement during the early years
of transplantation
• Nearly abandoned during the 1970’s and 1980’s
– adoption of brain death criteria
– better organ function with heart-beating donors
– poor organ function:
» hypoxia and hypotension during process of death
» warm ischemia time
• Worsening donor organ crisis as a result of superb
results with transplantation and an increase in patients
awaiting transplantation
• Organ procurement from DCD donors regaining
acceptance during late 1990’s
 Donation After Cardiac Death

DCD has emerged as a “standard of care”

• Institute of Medicine and DHHS endorsements
• HRSA OTBC – Increase DCD to 10% of all donations
• JCAHO – Hospital protocol standard in 2007
• UNOS/OPTN – Membership requirement in 2007
 Donation after Cardiac Death
Consent

• Decision to withdraw support

– No different than is current practice
– Decision made by patient, family, and medical team in
accord with hospital policy and procedure
– Decision is independent of decision to donate
• Decision to donate
– Family discussion with procurement coordinator
» Education and Counseling
– Assessment for donation
» Suitability of organs
» Likelihood of cardiac death within one hour of
withdrawal of support
 Donation After Cardiac Death
1993 - 2005
7.4%
600

500

400

300

200

100

0
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

WWW.USTRANSPLANT.ORG
 Donation After Cardiac Death
Liver Transplantation

UNOS
• Inferior graft survival with DCD donors
– 70% versus 80% at 1 year
• Inferior patient survival with DCD donors
– 80% versus 85% at 1 year
• Association between preservation time and graft failure
– 30% at 8 hours, 58% at 12 hours and 17% increase each
additional hour
• Poor results with older (age > 60 years) DCD donors
– 25% graft failure

Annals of Surgery 2004; 239:87

 Donation after Cardiac Death
Mayo Clinic Experience

• 12 DCD multiorgan procurement procedures

• 7 Mayo Clinic liver recipients
– includes 1 pediatric recipient of pediatric DCD donor
– no cholangiopathy
• 1 liver recipient at another transplant center
Living Donor Right Hepatectomy
Ex-vivo Split Liver Allograft
Jason and Stephanie
Jason and Stephanie
 Domino Liver Transplantation
Autosomal Dominant Amyloidosis

• Liver histologically normal

• Liver produces amyloid
• Problems from amyloid after 20 – 40 years
• Amyloid liver recipient selection
– Disadvantaged patients > 60 years
• Donor / recipient interaction
• Several dozen cases world-wide
Amyloid and Domino Transplant Recipients
December 25-26, 2002
 Focus on the Future
Strategic Initiatives

• Expanded criteria donor organ utilization

• Obesity – weight loss management protocol
• Hepatitis C – prevention and treatment of
recurrent disease
• Chemical dependency – programmatic
approach to evaluation and treatment
• Transplant Center quality initiative
• Commitment to excellence – outcome,
satisfaction
 US Center-Specific Data
Adult Patient Survival – July 2007

100
90
80 90.8 Observed
86.3 83.5
70 79.0 Expected
60
50
40
30
20
10
0
1 Year 3 Year

* Statistically higher than expected patient survival at 1 year

www.ustransplant.org
 US Center-Specific Data
Adult Patient Survival – July 2007
Deaths 1 year 3 year
Observed 17 31
Expected 29 42
Obs/Exp 60% 75%
 US Center-Specific Data
Adult Patient Survival – July 2007
Deaths 1 year 3 year
Observed 17 31
Expected 29 42
Obs/Exp 60% 75%
• 25 to 40% decrease in likelihood of
dying after liver transplantation at the
Mayo Clinic Rochester