Liver Transplantation at The Methodist Hospital

Report
Liver Transplantation at
SLEH/BCM
John A. Goss, MD
Professor of Surgery
Michael E. DeBakey
Department of Surgery
Baylor College of Medicine
Houston, Texas
History of Transplantation
1902
First attempt
at kidney
transplant
First attempt at
kidney transplant
with human kidney
First liver
transplant
1936
1963
1954
First successful
kidney transplant
First pediatric
living donor
liver transplant
1983
1989
Cyclosporine
FDA approved
First US adult living
donor liver
transplant
1994
1998
Tacrolimus
FDA approved
2002
MELD
implemented
Initial Kidney Transplant Attempts:
Year
Location
Surgeon
Procedure
1902
Lyon
Alex Carrel
Dog kidney tx into dog neck
1902
Vienna
Emerich Ulmann
Dog kidney tx into goat
1906
Lyon
Mathieu Jaboulay Pig kidney tx into
antecubital fossa
1909
Berlin
Ernest Unger
Monkey kidney tx into thigh
1936
Kherson
Yu Voronoy
First kidney tx using
cadaveric human donor
1954
Boston
Joseph Murray
First successful kidney tx
1956
Boston
Joseph Murray
First tx using
immunosuppression
First Successful Kidney
Transplant
Experimental Liver Transplantation
Initial Liver Transplant Attempts:
1963-1964
No. Location
Age Disease Survival
Death
1
Denver
3
BA
0 days
hemorrhage
2
Denver
48
HCC
22 days
sepsis, PE
3
Denver
68
HCC
7 days
sepsis, PE
4
Denver
52
HCC
6 days
liver failure
5
Boston
58
mets.
11 days
sepsis
6
Denver
29
HCC
23 days
sepsis
7
Paris
75
mets.
0 days
hemorrhage
Initial Liver Transplant Attempts:
First Liver Transplant
 March 1, 1963: First
attempted human
liver transplant
 July 23, 1967: First
successful human
liver transplant
Post-Moratorium Successes
 anti-lymphocyte
globulin (ALG) &
the “triple cocktail”
 improved organ
preservation
 definition of “brain
death”
Starzl TE. J Am Coll Surg 2002; 195:587.
• 1968 Ad Hoc Committee of Harvard Medical School
Published Criteria for Brain Death
• 1968 Uniform Anatomical Gift Act
• 1978 Uniform Brain Death Act
• 1983 NIH Consensus Development Conference:
• “…Liver Transplantation is a therapeutic modality
for end stage liver disease that deserves broader
application.”
• 1984 National Organ Transplant Act:
• Sale of organs prohibited
• Development of UNOS
Indications for Liver Transplant
Life-threatening and progressive irreversible liver
disease
2. Fulminant hepatic failure
3. Hepatopulmonary or hepatorenal syndrome
4. Worsening synthetic function
5. Ascites resistant to medical therapy
6. Hepatic encephalopathy
7. Variceal hemorrhage
8. Progressive malnutrition
9. Increasing fatigue that interferes with daily activities
10. Recurrent cholangitis
11. Development of hepatocellular carcinoma
1.
Etiology of Liver Disease
Other Viral
Metabolic
Autoimmune
ALF
Hepatitis C
HCV/EtOH
Cryptogenic
PBC/PSC
EtOH
Other
Indication for Liver Transplantation
Evaluation Process
Hepatologist
Transplant Surgeon
Cardiologist
Nurse Coordinator
Social Worker
Laboratory Studies
Imaging (CT or MRI)
List for Transplant
Relative Contraindications
Absolute Contraindications
Portal vein thrombosis
Pulmonary hypertension
Cholangiocarcinoma
HIV
Medical Management
Uncontrolled systemic infection
Extra-hepatic malignancies
Ongoing drug or alcohol use
Inability to comply
with post-transplant therapy
Liver Waitlist
Timing of Transplant
Organ Allocation 2002-present
MELD (Model of End Stage Liver Disease)
• Originally developed to evaluate mortality in
patients undergoing elective TIPS procedures
• Subsequently validated as predictive of survival
in patients with end stage liver disease
• 85% of time accurately predicts individuals
survival
• Only objective data used in calculation
MELD
R= (0.957 x Loge(creatinine mg/dl)
+ 0.378 x Loge(total bilirubin mg/dl)
+ 1.120 x Loge(INR) + 0.643)) x 10
MELD
3 Month Mortality
<10
10-19
20-29
30-39
>40
2-8%
6-29%
50-76%
62-83%
100%
Liver Allocation
• Status IA
• Status IB
• Local MELD/PELD
• Regional MELD/PELD
• National IA/IB
• National MELD/PELD
Deceased Donor Technique
Recipient Technique: Liver
Recipient Technique: Liver
Immunosuppression
Improvement in Patient Survival
100
Patient Survival %
80
60
40
20
0
0
1
2
3
4
Time After Transplantation (years)
Azathioprine
Cyclosporin-UW
Cyclosporin-EC
Tacrolimus
5
Improvement in Allograft Survival
100
Survival %
90
80
70
60
50
Time After Transplantation (years)
Before 1995
After 1995
US Survival: Adult Liver
100
95.2 97.1
86.5 89.5
90
80
75.8
79.9
70
60
Graft
Patient
50
40
30
20
10
0
1 Month
1 Year
3 Years
US Survival: Pediatric Liver
100
92.4
96.8
90
94.1
87.9
90.1
83.4
80
70
60
Graft
Patient
50
40
30
20
10
0
1 Month
1 Year
3 Years
Liver Transplantation • BCM initiated Recruitment in 1998
• 1 Hepatologist, 2 Surgeons, 1 Nurse
Coordinator
• 1 Social Worker, 1 Financial Coordinator,
HLA Blood Bank, etc.
• Development of Patient Care Protocols –
ICU, Anesthesia, OR Nurse
• Obtainment of UNOS Certification 6/98
Liver Transplantation • Opened program 7/1/98 – combined with
pediatric program at Texas Children’s
Hospital
• 1st resection 7/5/98
• 1st liver transplant 9/2/98
• 9 liver transplants in 1998 - All patients
survived with 14 day length of stay
Liver Transplantation• 17 Physicians - 9 Adult Hepatologists
6 Pediatric Hepatologists
2 Surgeons
• 14 Nurse Coordinators
• 5 Hepatology Nurses
• 5 Medical Assistants
• 2 Administrative Staff
• 3 Transplant programs
SLEH Liver Transplant Team
SLEH/BCM Administration
THI Nurse Coordinators
Margaret Van Bree, MHA, DrPH
Paul Klotman, MD
Todd Rosengart, MD
Rachel Goldsmith, MPA
Diesa Samp, BSN, RN, CCTC
Claudette Campbell, RN
Jeanette Cleveland, RN
Shannon Cook, RN
Norma Flores, RN
Felicia Franco, RN
Diana Gonzalez, RN
Demetrice Gray, RN
Yolanda Murray, RN
Wanda Samuels, RN
Tamara Stephens, RN
Physicians
John Goss – BCM
Blaine Hollinger-BCM
Khozema Hussein-BCM
Prasun Jalal-BCM
Saira Khaderi-BCM
Charles Phan-BCM
Christine O’Mahony- BCM
Gagan Sood, BCM
Rise Stribling- BCM
Norman Sussman-BCM
John Vierling- BCM
THI Anesthesiology
Pharmacy
Raymond Yau, PharmD
Social Work
Ann Holder, LCSW
Robin Kremer, LCSW
Dietary
Amy Cook, RD
C. David Collard, MD
Cardiology
Financial
Sayeed Feghali, MD
Deidra Lester
THI Pathology/Blood Bank/ Lab Med
Exercise Physiologist
Rhonda Shannon, MD
Fabian
Psychiatry
Jennifer Pate, M.D.
Pulmonary, Nephrology, Infectious Diseases, GI
Nursing Staff: CVOR, CV Recovery,
8CB 12 & 7 Tower
Diagnosis
6%
2%
8%
EtOH
9%
Cancer
22%
7%
HCV
Autoimmune
Other
Cryptogenic
46%
FHF
Primary Payor
15%
Medicare/
Medicaid
33%
Transplant
Network
Cash Pay
Insurance
3%
48%
Transplant Totals
120
120
16
95
100
80
66
60
51 13
73
18
20
94
20
5
10
20
0
1998*
2000
12
85
32
39
9
33
9
1
74
73
56
52
43
2002
17
105
104 100
75
12 43
3
9
83 30
110
14
24
55
13
1
66 67
40
105
119
26
8
53
114
2004
Adult
2006
VA
2008
Pediatric
63
2010
69
57
2012
51
2010: One Thousand Liver
Transplants
2010 Adult Liver Transplant Team
100%
99.3%
96.9%
94.9%
95%
89.5%
90%
87.1%
85%
79.9%
80%
75%
70%
1 Month
1 Year
3 Year
Patient Survival
SLEH
United States
100%
*
99.36%
95.10%
95%
90%
*
93.40%
86.50%
*
86.50%
85%
*Statistically
higher than
expected
SLEH
United States
80%
75.60%
75%
70%
1 Month
1 Year
Graft Survival
3 Year
2012 Summary
• Unadjusted patient and graft
survival: 98%
• Median length of stay: 9 days
• Operative time: 3 hours and 20
minutes
• Number of blood transfusions:
1.7 units of PRBCs
Future Directions
•Asian Liver Center
•Outreach clinics
•Improvement in length of stay
•Improvement in survival
•Telemedicine/ECHO
Liver Transplantation –
Education/Research
• Provide Clinical Environment for BCM 3rd Year Medical
Student and BCM General Surgery Residents
• TSMBE and ASTS Approved Liver Transplant
Fellowship
• AASLD Funded NP Fellowship
• Trained Murat Kilic, MD – Chief of Liver Transplantation
Izmir, Turkey
• 108 Peer-reviewed publications
• 102 National oral presentations
• TSMBE/ACGME Hepatology Fellowship
Liver Transplant Division:
Ongoing Research Projects
Research Division
Post-transplant
Lymphoma
Hepatocellular
carcinoma
Clinical
Research
Status of Tissue Bank
• >1400 tissue samples from 146 patients
• Sanger Sequencing of HCC Samples
• 300 amplicons over 30 genes
• 89 HCC samples with matched non tumor
tissue or blood
• 33 HCV, 3 EtOH, 1 BA, 49 HBV, 3 with no
underlying liver disease
• 16 Hepatoblastoma with non tumor tissue
• 4 Hepatic adenoma with non tumor tissue
Ongoing Projects
• Epigenetics of HCC
• Investigating differential methylation patterns in tumor
and non tumor tissue
• Gene expression profiling
• Developing cDNA libraries from mRNA
• Whole genome sequencing
• Select patients to have entire genome sequenced
• Testing new platforms
• New Next Generation sequencers to be tested on HCC
samples
• Development of collaborative tissue
exchange programs
• Vanderbilt, Baylor Dallas, Harvard, and Mayo Clinic
participating in the early stages of the development of an
HCC consortium
Future
Reduce Donor/Recipient Discrepancy
• Donor awareness campaigns
• Extended criteria/ asystolic donors
• Split liver transplantation
• Living-donor liver transplantation
• Xenotransplantation
Future
Bioartificial Liver
Stem Cells
Future
Tolerance
Future
Personalized Immunosuppression
• Increase selectivity, decrease
toxicity/side effects
• Pediatric transplantation
• Hepatitis C
• Coinfection
Future
Pharmacogenetics and Pharmacogenomics
Future
Primary Liver Tumors
• Hepatocellular carcinoma that
exceeds Milan Criteria
• Down-staging
• Presence of vascular invasion
• Genetics
• Choangiocarcinoma
• Previously considered a
contraindication to OLT
• Mayo Protocol: multimodality
neoadjuvant therapy
• Genetics
Conclusion
• Liver transplantation has produced a positive
impact on patients with advanced liver
disease
• Spectacular improvement have occurred
since the preliminary work of Dr. Starzl
• The advances in liver transplantation have
occurred in a short 45 years and provide a
base for future advances

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