Lewis Teperman, Director of Transplantation at NYU School of Medicine, gave an annual presentation to nurses on updates and innovations in liver transplantation. Key points from the presentation include: 1) The number of patients on the liver transplant waiting list continues to grow while transplants and donation have remained relatively stable; 2) Older donors and those with certain risk factors can now be successfully used for liver transplantation; and 3) The MELD scoring system was implemented to better prioritize the sickest patients on the waiting list based on objective medical criteria rather than subjective measures.

1. UPDATE AND INNOVATIONS IN
LIVER TRANSPLANTATION
Lewis Teperman, M.D.
Director of Transplantation
Vice Chairman of Surgery
NYU School of Medicine
Annual Presentation to Nurses
June 28, 2013
1

2. 2

3. Sources: (1) 2007 OPTN/SRTR Annual Report Tables 1.3 and 1.7; and (2) http://optn.transplant.hrsa.gov/ar2009/
Number of Patients on UNOS Liver Waiting List
(as of
3/14/2011 = 16,853)
Transplant
s
3

4. Causes of Death in 262 DonorsCauses of Death in 262 Donors
41
27
74
51
15
10
8
5
6
4
4
4
4
3
2
2
2
1
0 10 20 30 40 50 60 70 80
MOTOR VEHICLE ACCIDENT
GUN SHOT WOUND
SUBARACHNOID BLEED/CVA
HEAD INJURY
FALLING
INTRACRANIAL ANEURYSM
ASPIRATION
MENINGITIS
BRAIN TUMOR
IATROGENIC
CHILD ABUSE
DROWNING
DRUG INTOXICATION
SUDDEN INFANT DEATH
SEIZURE
DIABETES
CHOKING
SPORTS ACCIDENT

5. New York Organ Donor NetworkNew York Organ Donor Network
 New York is saferNew York is safer
 Crime is downCrime is down
 Vehicular accidents are downVehicular accidents are down
Organ Donation
Living Donation 20%
Deceased Donation 10%
Import Organ Offers 75%
5

6. Doctors Confirm West Nile in a 4thDoctors Confirm West Nile in a 4th
Transplant PatientTransplant Patient
 Doctors have confirmed that a woman in Florida is the fourth personDoctors have confirmed that a woman in Florida is the fourth person
to have contracted West Nile virus after receiving an organto have contracted West Nile virus after receiving an organ
transplanted from a single donor who had the virus, a federal healthtransplanted from a single donor who had the virus, a federal health
official said last night.official said last night.
 Finding the virus in all four organ recipients "very strongly suggestsFinding the virus in all four organ recipients "very strongly suggests””
that the disease was transmitted by the organs rather than bythat the disease was transmitted by the organs rather than by
mosquito bites, said the official, Dr. Lyle Petersen, a West Nile expertmosquito bites, said the official, Dr. Lyle Petersen, a West Nile expert
at the Centers for Disease Control and Prevention.at the Centers for Disease Control and Prevention.
 ------ The New York TimesThe New York Times
6

7. WEST NILE VIRUS
• West Nile, a flavivirus, is a relatively
new pathogen to the U.S.
• Other flaviviruses include:
- Yellow fever
- Dengue
- Saint Louis Encephalitis
LW Teperman, MD, T Diflo, MD, A Fahmy, MB, GR Morgan, MD, et al. “West Nile Virus Infections in Organ Transplant Recipients---
New York and Pennsylvania, August---September, 2005.” MMWR Disptach of CDC October 5, 2005: 54 (Dispatch); 1-3.
7

8. West Nile VirusWest Nile Virus
Approximate Geographic Range in 1998Approximate Geographic Range in 1998
8

9. 9

10. 2005
• 2,949 cases
• 628 counties
• 42 states
10

11. 0
20
40
60
80
100
120
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
Te
Neurologic
Temp Curve
OLTX T 105° Weakness
Seizures
Flaccid
Paralysis
68 days
expired
PATIENT COURSE
OMR-IgG-amIgG
300
Treatment
AST
FK/SM/ZENEPAX
CELLCEPT FK / DC’d
40.6° C 40.3° C
37.6° C
311
35
400
1137
43
DC’d
Cellcept
WNV
11

12. Tumor ConveyanceTumor Conveyance
““Teen Organ Donor's Gift Turns Tragic”Teen Organ Donor's Gift Turns Tragic”11
““Transmission of Anaplastic Large CellTransmission of Anaplastic Large Cell
Lymphoma via Organ Donation AfterLymphoma via Organ Donation After
Cardiac Death”Cardiac Death”22
1. SAG HARBOR, N.Y., April 1, 2008, Nancy Cordes, CBS News Correspondent
2. JW Harbell, TB Dunn, M Faudia, DG John, AS Goldenberg and LW Teperman.. American Journal of Transplantation,
January 2008; Vol. 1; Issue I; 238-244.
12

13. Transmission of Anaplastic
Large Cell Lymphoma via
Organ Donation After
Cardiac Death
J.W. Harbell, T.B. Dunn, M. Fauda, D.G.John, A.S. Goldenberg, L.W. Teperman;
AJT:2008; 8, pps 238-244.

14. 14

15. Donor-Derived Disease Transmission EventsDonor-Derived Disease Transmission Events
in the United States: Data Reviewedin the United States: Data Reviewed
by the OPTN/UNOS Disease Transmissionby the OPTN/UNOS Disease Transmission
Advisory CommitteeAdvisory Committee
M. G. Ison,*, J. Hager, E. Blumberg,M. G. Ison,*, J. Hager, E. Blumberg,
J. Burdick, K. Carney, J. Cutler, J. M. DiMaio,J. Burdick, K. Carney, J. Cutler, J. M. DiMaio,
R. Hasz, M. J. Kuehnert, E. Ortiz-Rios,R. Hasz, M. J. Kuehnert, E. Ortiz-Rios,
L. Teperman and M. NalesnikL. Teperman and M. Nalesnik
American Journal of Transplantation 2009; 9: 1–7American Journal of Transplantation 2009; 9: 1–7
15

16. Table 5: Reports made to DTAC regarding a potential donor-
derived malignancy transmission
2005-2007
Malignancies Donor
Reports1
Confirmed
Recipients2
Recipient
Deaths3
Renal Cell Carcinoma 25 3 0
Lung adenocarcinoma 5 2 2
Glioblastoma
multiforme
4 1 1
Lymphoma 3 4 2
Metastatic Melanoma 3 2 1
Prostate
adenocarcinoma
2 0 0
OTHERS X X X
TOTALS 55 15 6
1. Number of donors reported possible donor-derived disease transmission. 2. Number of recipients with confirmed (proven, probable or possible) donor-derived
disease. 3. Number of recipients who died as the result of a donor-derived disease transmission.

17. ““The liver does notThe liver does not
undergo senescence.”undergo senescence.”
-Hans Popper, MD-Hans Popper, MD

18. The Successful Use of OlderThe Successful Use of Older
Donors for LiverDonors for Liver
TransplantationTransplantation
L. Teperman, L. Podesta, L. Mieles, T. StarzlL. Teperman, L. Podesta, L. Mieles, T. Starzl
JAMA 1989; 262:2837JAMA 1989; 262:2837

19. Donor FactorsDonor Factors
 Age BarrierAge Barrier > 80 Years> 80 Years
 Fat Content:Fat Content: macro vs. micromacro vs. micro
 Length of stayLength of stay > 10 days> 10 days
 HypernatremiaHypernatremia
19

20. Expanded Criteria DonorExpanded Criteria Donor
 Define Relative Risk(RR) of FailureDefine Relative Risk(RR) of Failure
 RR 1.7: 70% greater risk of failureRR 1.7: 70% greater risk of failure
FactorFactor RRRR P-ValueP-Value
Donor Age 40 to 49Donor Age 40 to 49 1.161.16 0.00060.0006
Donor Race BlackDonor Race Black 1.191.19 0.00010.0001
DCD LiverDCD Liver 1.521.52 0.00060.0006
Partial / Split LiverPartial / Split Liver 1.531.53 0.00010.0001
Donor Age 70 or AboveDonor Age 70 or Above 1.631.63 0.00010.0001
20

21. 19961991
Obesity Trends* Among U.S. Adults
BRFSS, 1991, 1996, 2004
(*BMI ≥30, or about 30 lbs overweight for 5’4” person)
No Data <10% 10%–14% 15%–19% 20%–24% ≥25%
2004
Source Mokdad A.H., et all JAMA 2003,289-1 21

22. Obesity Trends* Among U.S. Adults
BRFSS, 2011
http://feww.files.wordpress.com/2011/07/obesity-2011-feww1.png
22

23. 23

24. Retransplant Rates in RegionRetransplant Rates in Region
vs. the USvs. the US
13.4
10.3
6.7
4.9
8.4
5.6
0
2
4
6
8
10
12
14
ECD Non ECD Overall
Region 9 Rest of Country
RetransplantRates(%)
NYU
5%
24

25. Utility vs. EquityUtility vs. Equity

26. Old Allocation SystemOld Allocation System
Child-Turcotte-Pugh Scoring System to Assess
the Severity of Liver Disease
* For cholestatic liver diseases, these values for bilirubin are to be submitted for the values above.
Points 1 2 3
Encephalopathy None 1-2 3-4
Ascites Absent Slight or At least
controlled moderate
by diuretics despite diuretics
Bilirubin(mg/dL) <2 2-3 >3
Albumin >3.5 2.8-3.5 <2.8
Prothrombin time <1.7 1.7-2.3 >2.3
(seconds prolonged)
or INR
For PBC, PSC or other <4 4-10 >10
cholestatic liver diseases:
Bilirubin (mg/dL)*
26

27. Problems with CTP ScoreProblems with CTP Score
 Limited numberLimited number ofof categoriescategories
 LimitedLimited discriminating abilitydiscriminating ability
 UsesUses subjective parameterssubjective parameters -- gaminggaming
 LaboratoryLaboratory variabilityvariability (protime, albumin)(protime, albumin)
 Never validatedNever validated
 CreatinineCreatinine not includednot included
27

28. Q: What is MELD?Q: What is MELD?
A: Disease Severity ScoreA: Disease Severity Score

29.  90% Survival Probability on the waitlist90% Survival Probability on the waitlist
 VariablesVariables
 BilirubinBilirubin
 CreatinineCreatinine
 INRINR
““ CHANGE REAGENT”CHANGE REAGENT”
Liver disease etiology (deleted)Liver disease etiology (deleted)
MELD MODEL:MELD MODEL:
Predicts Survival in TIPS Patient
?
29

30. Creatinine Bilirubin INR Dialysis? HCC? MELD
Person #1 0.8 0.3 1.04 N N 6
Person #2 1.1 1.4 1.14 N N 10
Person #3 3.2 1.0 1.03 N N 18
Person #6 8.9 0.6 1.01 Y N 20
Person #4 1.8 1.6 2.00 N N 22
Person #5 0.9 1.7 1.26 N 2 – 5 cm* 22
Person #7 3.5 12.0 1.56 N N 33
MELD EquationMELD Equation
 MELD = (0.957 x LN (creatinine) + 0.378 xMELD = (0.957 x LN (creatinine) + 0.378 x
LN (bilirubin) + 1.12x LN(INR) + 0.643) x 10LN (bilirubin) + 1.12x LN(INR) + 0.643) x 10
 Capped at 40Capped at 40
30

31. HCC: Extra CreditHCC: Extra Credit
 Patients meeting criteria receivePatients meeting criteria receive 2222 points.points.
 After a three-month reevaluation patientsAfter a three-month reevaluation patients
receive additional points.receive additional points.
 Thereafter they receive additional pointsThereafter they receive additional points
every three months.every three months.
31

32. Indications for TransplantationIndications for Transplantation
NYUC Txps 2007 32

33. Hepatitis C Tumor BurdenHepatitis C Tumor Burden
 4 million US Patients4 million US Patients
 1 million Cirrhotics (10 years)1 million Cirrhotics (10 years)
 1/4 million HCC1/4 million HCC (10 years)(10 years)
33

34. Lewis Teperman, M.D.

35. Abdominal Organ ClusterAbdominal Organ Cluster
Transplantation for the Treatment ofTransplantation for the Treatment of
Upper Abdominal MalignanciesUpper Abdominal Malignancies
Thomas E Starzl MD, PHD; Satoro Todo MD; Andreas Tzakis MD; Luis Podesta MD;
Luis Mieles MD, Anthony Demetris MD, Lewis Teperman MD; Rick Selby MD; William
Stevensen MD; Andre Steiber MD; Robert Gordon MD; Shunzaburo Iwatzuki MD
35

36. 36

37. OLT Survival Milan CriteriaOLT Survival Milan Criteria
60 1812 3024 4236 48
20
0
40
60
100
80
Months
Probability(%)
Mazzaferro, V. N Engl J Med 199637

38. HCCHCC
 While we wait, the tumor grows!While we wait, the tumor grows!
 Treatment is appropriateTreatment is appropriate
 Are 6 cm lesions really more deadly thanAre 6 cm lesions really more deadly than
5 ?5 ?
 Exceptional case review (RRB)Exceptional case review (RRB)
John Roberts, UCSF, AJT 2006;
Yao, et al. Am J Transplant. 2007;7:2587-2596. 38

39. HCC Recurrence after OLTHCC Recurrence after OLT
5040 6010 3020
.2
0
.4
.6
1.
.8
Months
Recurrence
.3
.5
.7
.9
.1
No Vascular Invasion
Vascular Invasion
Hemming, A. Ann Surg 2001
0
39

40. HepatomasHepatomas
 Initial MELD ExceptionInitial MELD Exception
 29 points29 points
 ~ 20% of transplants~ 20% of transplants
 20-24 points20-24 points
 Excellent SurvivalExcellent Survival
 MELD is Evolving!MELD is Evolving!
 Consider living donationConsider living donation
40

41. Strategies for Long WaitingStrategies for Long Waiting
TimeTime
TACETACE
Living Donor TransplantLiving Donor Transplant
41

42. Chemoembolization (CE) forChemoembolization (CE) for
HCCHCC
 Femoral artery CatheterizationFemoral artery Catheterization
 3 Elements3 Elements
 LipiodolLipiodol
 Chemotherapeutic agent(adriamycin, cisplatinum)Chemotherapeutic agent(adriamycin, cisplatinum)
 Embolizing Agent(Gelform, Avitene)Embolizing Agent(Gelform, Avitene)
 Selective hepatic arterial localizationSelective hepatic arterial localization
 ““Kill” RatesKill” Rates
 Without significant complicationsWithout significant complications
*Neo adjuvant: Thalidomide (-)*Neo adjuvant: Thalidomide (-)
(+) NEXAVAR MULTI-CENTER(+) NEXAVAR MULTI-CENTER
TRIAL 2012TRIAL 2012 42

43. 43

44. 44

45. ChemoembolizationChemoembolization
Random Effects ModelRandom Effects Model
63
95
503
80
73
79
112
Favors Treatment Favors Control
0.10.01 10.5 2 10010
Lin, Gastroenterology 1988
Overall
GETCH NEJM 1995
Bruix, Hepatology 1998
Pelletier, J Hepatology 1998
Lo, Hepatology 2002
Lovett, Lancet 2002
OR (95% CI)
P=0.017
Llovet, J Hepatology 2003
45

46. Patient Survival after liverPatient Survival after liver
transplantation:transplantation:
Benign vs. Malignant diseaseBenign vs. Malignant disease
Months after 46

47. TRANSPLANTATION FOR HEPTRANSPLANTATION FOR HEP
B HBIG TREATMENTB HBIG TREATMENT
Months
HBIG HBIG HBIG
47

48. There is NO consensus on optimalThere is NO consensus on optimal
duration of HBIG, dose, or mode ofduration of HBIG, dose, or mode of
administration.administration.
-- Lewis TepermanLewis Teperman
10/15/200610/15/2006
48

49. Viral DNA Chain TerminatorsViral DNA Chain Terminators
 GanciclovirGanciclovir
 FamciclovirFamciclovir
 LamivudineLamivudine
 AdefovirAdefovir
 EntecevirEntecevir
 TenofovirTenofovir
 EmtricitabineEmtricitabine
49

50. A Randomized Trial of HBIGA Randomized Trial of HBIG
Withdrawal UsingWithdrawal Using
Emtricitabine/Tenofovir DF inEmtricitabine/Tenofovir DF in
Post-Liver Transplant RecipientsPost-Liver Transplant Recipients
L TepermanL Teperman11
, J Spivey, J Spivey22
, F Poordad, F Poordad33
, T Schiano, T Schiano44
, N Bzowej, N Bzowej55
,,
S PungpapongS Pungpapong66
, P Martin, P Martin77
, D Coombs, D Coombs88
, K Hirsch, K Hirsch88
, J Anderson, J Anderson88
and F Rousseauand F Rousseau88
11
The Mary Lea Johnson Richards Organ Transplantation Center,The Mary Lea Johnson Richards Organ Transplantation Center,
New York University Medical Center, New York, NY;New York University Medical Center, New York, NY; 22
Emory Healthcare, Atlanta, GA;Emory Healthcare, Atlanta, GA;
33
Cedars-Sinai Medical Center, Los Angeles, CA;Cedars-Sinai Medical Center, Los Angeles, CA; 44
Recanati/Miller Transplantation Institute,Recanati/Miller Transplantation Institute,
Mount Sinai Hospital, New York, NY;Mount Sinai Hospital, New York, NY; 55
California Pacific Medical Center, San Francisco, CA;California Pacific Medical Center, San Francisco, CA;
66
Mayo Clinic Jacksonville, Jacksonville, FL;Mayo Clinic Jacksonville, Jacksonville, FL; 77
Schiff Liver Institute,Schiff Liver Institute, University of Miami,University of Miami,
Miller School of Medicine, Miami, FL;Miller School of Medicine, Miami, FL; 88
Gilead Sciences Inc., Durham, NCGilead Sciences Inc., Durham, NC

51. BackgroundBackground
 HBIG prophylaxis is routinely prescribed toHBIG prophylaxis is routinely prescribed to
prevent HBV recurrence post-orthotopic liverprevent HBV recurrence post-orthotopic liver
transplantation (OLT)transplantation (OLT)
 HBIG prevents recurrence byHBIG prevents recurrence by neutralizingneutralizing HBsAgHBsAg
 Long-term prophylaxis with HBIG is inconvenientLong-term prophylaxis with HBIG is inconvenient
and expensive, but is the mainstay of post-and expensive, but is the mainstay of post-
transplant therapy.transplant therapy.
51

52. Cost of HBIG in Relation with HBIG Dosing and Strategy of
Administration in Patients Receiving HBIG + Lamivudine
Yearly cost of different schedules of HBIg administration in Euros. The “on demand” schedule using
2,000 IU of HBIg allows a savings of over 50% compared with fixed monthly doses of 5,000 IU.
Di Paolo et al. Transplantation 2004; 77: 1203-
1208.
52

53. AimAim
 This ongoing randomized study (Study 107)This ongoing randomized study (Study 107)
evaluates the safety andevaluates the safety and efficacy of TVDefficacy of TVD
with/without HBIGwith/without HBIG in preventing recurrence ofin preventing recurrence of
CHB post OLTCHB post OLT
 The aim of thisThe aim of this interim analysisinterim analysis is to evaluate theis to evaluate the
efficacy, safety and tolerability of TVD in thisefficacy, safety and tolerability of TVD in this
populationpopulation
53

54. Patient Disposition
Screened
N=51
Enrolled
N=40
Randomized at Week 24
N=37
Discontinued N=3
TVD+HBIG
N=19
TVD
N=18
Completed Week 72 N=15
Completed Week 96 N=11
Completed Week 72 N=14
Completed Week 96 N=12
Discontinued N=1
Death N=1
Discontinued N=1

55. Virologic OutcomesVirologic Outcomes
 No detectable HBV DNA (169No detectable HBV DNA (169
copies/mL; lower limit of quantitation)copies/mL; lower limit of quantitation)
in either groupin either group
 No HBsAg positivityNo HBsAg positivity
55

56. Hepatitis CHepatitis C
 Most common indication forMost common indication for
transplantation 25 - 45%transplantation 25 - 45%
 95% of recipients persist with antibody to C95% of recipients persist with antibody to C
 At least 50% develop active hepatitis onAt least 50% develop active hepatitis on
biopsybiopsy
 It is unknown how many progress to aIt is unknown how many progress to a
chronic statechronic state
56

57. Treatment for Hepatitis CTreatment for Hepatitis C
 InterferonInterferon
 RibavirinRibavirin
 Pegylated - InterferonPegylated - Interferon
 PegasysPegasys
 PEG-IntronPEG-Intron
 Protease Inhibitors 2011Protease Inhibitors 2011
 NYU post tx pilot 7/15 negNYU post tx pilot 7/15 neg
-TIMING--TIMING-
57

58. Baylor Zenapax Trial
Steroid Sparing
I L 2 Receptor Antagonist Induction
Randomized Controlled Trial
Results:
No Difference in Hepatitis C Recurrence,
Diabetes, or Rejection
November 2005
Fasola, C G., Heffron, T. G., Sher, L., Douglas, D. D., Brown, R., Ham, J,. Teperman, L.,…et al. “Multicenter Randomized Hepatitis C
(HCV) Three Trial Post Liver Transplantation (OLT): A Preliminary Report.” Transplantation. 78(2) Supplement 1: 146, July 27, 2004.58

59. A Randomized Multicenter Study
Comparing Efficacy and Safety of
Steroid-Free and Standard
Immunosuppression for Liver
Transplantation Recipients with
Chronic Hepatitis C
(submitted)
Goran B. Klintmalm1
, Gary L. Davis1
, Lewis Teperman2
, George J. Netto3
, Ken Washburn4
, Steven Rudich5
, Elizabeth Pomfret6
, Hugo
E. Vargas7
, Robert Brown8
, Devin Eckhoff9
, Timothy Pruett10
, John Roberts11
, David C. Mulligan7
,Michael Charlton12
, Thomas G.
Heffron13
, John Ham14
,David Douglas7
,Linda Sher15
,Prabhakar Baliga16
, Milan Kinkhabwala8
, Baburao Koneru17
,Michael Abecassis18
,
Michael Millis19
, Linda W. Jennings1
, Carlos G. Fasola13
1
Baylor University Medical Center, Dallas, TX; 2
New York University Medical Center, NY; 3
Johns Hopkins Medical Institutions,
Baltimore, MD; 4
University of Texas Health Science Center at San Antonio; 5
University of Cincinnati, Cincinnati, OH; 6
Lahey Clinic,
Burlington, MA; 7
Mayo Clinic, Scottsdale, AZ; 8
New York Presbyterian Hospital, New York, NY; 9
University of Alabama – Birmingham, AL; 10
University of Virginia, Charlottesville, VA; 11
University of California, San Francisco, CA; 12
Mayo Clinic, Rochester, MN; 13
Emory University
School of Medicine, Atlanta, GA (current address: Scott and White Clinic, Temple, TX); 14
Oregon Health Sciences University, Portland, OR; 15
University of Southern California, Los Angeles, CA; 16
Medical College of South Carolina, Charleston, SC; 17
University of Medicine and
Dentistry of New Jersey, Newark NJ; 18
Northwestern Memorial Hospital, Chicago, IL; 19
University of Chicago, Chicago, IL
59

60. ““The challenge ofThe challenge of
transplant surgery is NOTtransplant surgery is NOT
the surgery”the surgery”
60

61. 61

62. Immunologic ArmamentariumImmunologic Armamentarium
(Arsenal)(Arsenal)
 Vietnam ConflictVietnam Conflict
 ImuranImuran -- Ground TroopsGround Troops
 SteroidsSteroids -- Light ArtilleryLight Artillery
 Cold WarCold War
 CyclosporineCyclosporine -- F16F16
 Okt3Okt3 -- “Tactical” warhead / cruise missile“Tactical” warhead / cruise missile
 Desert StormDesert Storm
 PrografPrograf -- Smart BombSmart Bomb
 NeoralNeoral -- Modified F16Modified F16
 Cell CeptCell Cept -- B2 stealth bomberB2 stealth bomber
 IL2 Receptor AbsIL2 Receptor Abs -- X - PlaneX - Plane
 RapamycinRapamycin - Osprey Transport- Osprey Transport
 RapamuneRapamune - Modified Osprey Transport- Modified Osprey Transport
 War on TerrorWar on Terror
 ThymoglobulinThymoglobulin -- Biologic WeaponBiologic Weapon
 CampathCampath - Modified Biologic Weapon- Modified Biologic Weapon
62

63. Risk of Chronic Renal FailureRisk of Chronic Renal Failure
 A 15-year experience at Baylor MedicalA 15-year experience at Baylor Medical
Center found that at 13 years after liverCenter found that at 13 years after liver
transplantationtransplantation
 Incidence of severe renal dysfunction ofIncidence of severe renal dysfunction of
18.1%18.1%
 Chronic renal failure in 8.6% of patientsChronic renal failure in 8.6% of patients
 ESRD in 9.5% of patientsESRD in 9.5% of patients
Gonwa TA et al. Transplantation 2001;72:1934-1939.
63

64. Risk of Chronic Renal FailureRisk of Chronic Renal Failure
Number at RiskNumber at Risk
Heart-Heart-
lunglung
576576 375375 295295 219219 194194 156156 133133 107107 7272 4646 3030
HeartHeart 24,01424,014 19,88519,885 17,23817,238 14,68714,687 12,34112,341 10,02210,022 7,9977,997 6,1046,104 4,5264,526 3,0963,096 1,9911,991
IntestineIntestine 228228 152152 110110 8484 5757 3333 2323 1313 88 55 55
LiverLiver 36,84936,849 28,49528,495 24,04124,041 19,50819,508 15,72415,724 12,56412,564 9,8449,844 7,3457,345 5,2925,292 3,6143,614 2,2612,261
LungLung 7,6437,643 5,6335,633 4,3164,316 3,1843,184 2,3272,327 1,6291,629 1,1361,136 745745 468468 258258 133133
Ojo AO, et al. N Engl J Med 2003;349:931-40.
Months since Transplantation
CumulativeIncidence
ofChronicRenalFailure
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0.00
0 12 24 12010884 967236 48 60
Lung
Intestine
Heart
Liver
Heart–lung
64

65. Calcineurin inhibitor-freeCalcineurin inhibitor-free
maintenance withmaintenance with
mycophenolatemycophenolate
mofetil/sirolimus in livermofetil/sirolimus in liver
transplant recipients: Save-transplant recipients: Save-
the-Nephron Trialthe-Nephron Trial
(submitted)(submitted)
L .Teperman,L .Teperman,11
D. Moonka,D. Moonka,22
A.Sebastian,A.Sebastian,33
L. Sher,L. Sher,44
P. Marotta,P. Marotta,55
C. Marsh,C. Marsh,66
B. Koneru,B. Koneru,77
J. Goss,J. Goss,88
D. Preston,D. Preston,99
and J. Robertsand J. Roberts1010
11
New York University School of Medicine, New York, New York;New York University School of Medicine, New York, New York; 22
Henry Ford Health Systems, Detroit, Michigan;Henry Ford Health Systems, Detroit, Michigan; 33
Integris Baptist MedicalIntegris Baptist Medical
Center, Oklahoma City, Oklahoma;Center, Oklahoma City, Oklahoma; 44
University of Southern California, Los Angeles, California;University of Southern California, Los Angeles, California; 55
London Health Sciences Hospital,London Health Sciences Hospital,
London, Ontario, Canada;London, Ontario, Canada; 66
Scripps Green Hospital, La Jolla, California;Scripps Green Hospital, La Jolla, California; 77
University of Medicine and Dentistry of New Jersey, Newark,University of Medicine and Dentistry of New Jersey, Newark,
New Jersey;New Jersey; 88
Saint LukeSaint Luke’s Episcopal Hospital, Houston, Texas;’s Episcopal Hospital, Houston, Texas; 99
Genentech, South San Francisco, California;Genentech, South San Francisco, California; 1010
University of California, SanUniversity of California, San
Francisco, CaliforniaFrancisco, California
Lew, This version contains comments from LS, JR, and DM. PM provided feedback of no comments. Lew, This version contains comments from LS, JR, and DM. PM provided feedback of no comments. 65

66. STN Trial DesignSTN Trial Design
MMF +MMF + tacrolimustacrolimus
±± corticosteroidscorticosteroids
MMF + cyclosporine
± corticosteroids
MMF + tacrolimusMMF + tacrolimus
MMF + cyclosporine
MMF + sirolimusMMF + sirolimus
MMF + sirolimusMMF + sirolimus
Post-randomizationPost-randomization
1 year1 year
Pre-randomizationPre-randomization StableStable
4 – 124 – 12
WW
EE
EE
KK
SS
PP
OO
SS
TT
--
TT
XX
2 years2 years
ScreeningScreening Enrollment
66

67. Mean %Mean % Increase in CalculatedIncrease in Calculated
GFRGFR
Baseline to Month 6Baseline to Month 6
N = 84
55.8±±1.91.9
N = 86
50.6±±1.91.9
0
5
10
15
20
25
30
35
MeanPercentIncrease
(±SEM)
MMF/SRL
MMF/CNI
3.2
40
Baseline GFR ± SEM (mL/min)
29.2
67

68. ConclusionsConclusions
 At leastAt least 62%62% of individuals are able toof individuals are able to toleratetolerate aa
maintenance regimen of MMF/SRL and willmaintenance regimen of MMF/SRL and will
benefitbenefit
 In the short term,In the short term, MMF/SRL improvesMMF/SRL improves renalrenal
functionfunction when compared to CNI-containingwhen compared to CNI-containing
regimensregimens
 The addition ofThe addition of lipid-lowering agentslipid-lowering agents may bemay be
necessary in patients receiving MMF/SRLnecessary in patients receiving MMF/SRL
 Complete follow-up of the 294Complete follow-up of the 294 patients willpatients will
provide a moreprovide a more statisticallystatistically robust conclusionrobust conclusion
about the long-term effect of this regimenabout the long-term effect of this regimen
68

69. Donor and NYU TimelineDonor and NYU Timeline
1999 Living Donation (Right Lobe Adult)
1997 Split Livers (peds) (Adult)
1990 Living Donation
Lateral Segment (peds)
1988 Reduced Sized Grafts (peds)
1963 University Hospital Built
1965 1st Successful
Liver Transplant
New Transplant Regulations
69

70. DONOR RISKSDONOR RISKS
New York Newsday, March 13, 2002
70

71. Transplant Chief at Mt. Sinai Quits Post inTransplant Chief at Mt. Sinai Quits Post in
Wake of InquiryWake of Inquiry
 A week after Mount Sinai Medical Center was cited byA week after Mount Sinai Medical Center was cited by
the state for dozens of serious violations, the chief of itsthe state for dozens of serious violations, the chief of its
liver transplant center has stepped down and the entireliver transplant center has stepped down and the entire
program will be restructured, hospital officialsprogram will be restructured, hospital officials
announced yesterday.announced yesterday.
 ------ The New York TimesThe New York Times
71

72. Summer of 2010Summer of 2010
 2 Recent U.S. Deaths2 Recent U.S. Deaths
 ColoradoColorado
 MassachusettsMassachusetts
72

73. New York StateNew York State
Report of the Subcommittee on DonorReport of the Subcommittee on Donor
Perioperative Care and Facility ReportPerioperative Care and Facility Report
Lewis Teperman M.D., Chair
73

74. New Preoperative Care RegsNew Preoperative Care Regs
1.1. Psychiatric EvaluationPsychiatric Evaluation
2.2. Bank BloodBank Blood
3.3. StaffStaff
1.1. 2 donor surgeons*2 donor surgeons*
2.2. A third transplant surgeon*A third transplant surgeon*
3.3. Anesthesia (2 attendings)Anesthesia (2 attendings)
4.4. Post operative carePost operative care
1.1. ICU (days 0 - 1)ICU (days 0 - 1) 1 Nurse / 2 Patients1 Nurse / 2 Patients
2.2. FloorFloor 1 Nurse / 4 patients1 Nurse / 4 patients
3.3. ResidentsResidents (pgy2) / NP(pgy2) / NP 24/724/7
5.5. RegistryRegistry
1.1. OutcomeOutcome
* Qualified
74

75. Living Donor RecipientsLiving Donor Recipients
 InclusionInclusion
 Listed with UNOS and must have a significantListed with UNOS and must have a significant
complication of liver diseasecomplication of liver disease
 Relative ExclusionsRelative Exclusions
 MELD > 25MELD > 25
 Cholangio CarcinomaCholangio Carcinoma
 ExclusionsExclusions
 AFHFAFHF
 Retransplant for CRetransplant for C
 Acute Alcoholic HepatitisAcute Alcoholic Hepatitis
75

76. HCC: Extra CreditHCC: Extra Credit
Is Living Donation justified?Is Living Donation justified?
 Patients meeting criteria receivePatients meeting criteria receive 2222
points.points.
 After a three-month reevaluationAfter a three-month reevaluation
patients receive additional points.patients receive additional points.
 Thereafter they receive additionalThereafter they receive additional
points every three months.points every three months.
76

77. Hepatoma PredictorHepatoma Predictor
LDLT and Waiting List TimeLDLT and Waiting List Time
20 64 108 1412 1816
2
0
4
8
12
10
Waiting list time (months)
Recipientlifeexpectancy(years)
2220 24
6
14
5 yr survival after DLT 70%
DLT drop out 2%/month
DLT drop out 4%/month
Immediate LDLT
Sarasin, F. Hepatology 200177

78. $$
No Selling of OrgansNo Selling of Organs
78

79. Donor CandidacyDonor Candidacy
Requirements (1)Requirements (1)
 Emotionally relatedEmotionally related
 Age 18 - 60Age 18 - 60
 Blood Type CompatibleBlood Type Compatible
A AA A
O O, B, A, ABO O, B, A, AB
79

80. MELD Score Comparison of CadavericMELD Score Comparison of Cadaveric
vs. Living Related Donorsvs. Living Related Donors
 Average Living Donor MELD Score:Average Living Donor MELD Score:
17.417.4
 Average Cadaveric MELD Score:Average Cadaveric MELD Score:
3232
80

81. 81

82. 1% Rule1% Rule
 70kg recipient needs a 700cc liver graft70kg recipient needs a 700cc liver graft
(1% GRWR)(1% GRWR)
 1% mortality1% mortality
(Actually ~0.05% but over emphasize to(Actually ~0.05% but over emphasize to
define risk)define risk)
82

83. Living DonorLiving Donor
 Right Hepatic resectionRight Hepatic resection
 50% - 65% of the hepatic mass50% - 65% of the hepatic mass
 Right is RightRight is Right
 Left hepatic resections will haveLeft hepatic resections will have
more complicationsmore complications
83

84. Living DonorsLiving Donors
What the Surgeon Needs to Know:What the Surgeon Needs to Know:
 Liver ParenchymaLiver Parenchyma
 Right lobe volumeRight lobe volume
 Exclude fattyExclude fatty
infiltrationinfiltration
 Characterize lesionsCharacterize lesions
 Hepatic arteriesHepatic arteries
 Arterial variantsArterial variants
 RHA originRHA origin
 Portal veinsPortal veins
 PV variants, RPVPV variants, RPV
originorigin
 Hepatic veinsHepatic veins
 RHV lengthRHV length
 MHV branches to rightMHV branches to right
lobelobe
 Inferior accessory HVInferior accessory HV
 Biliary ductsBiliary ducts
 Biliary variantsBiliary variants
 Rt lateral duct originRt lateral duct origin
84

85. Volumetric MRVolumetric MR
CholangiographyCholangiography
Lee VS, Teperman L, et Al. AJR, 2001.
85

86. CT CholangiographyCT Cholangiography
 Higher SpatialHigher Spatial
Resolution than MRResolution than MR
 Shorter Exam TimeShorter Exam Time
 Radiation DoseRadiation Dose
 Contrast AgentContrast Agent
86

87. Donor Rule #2Donor Rule #2
 Know the donorKnow the donor’s anatomy prior to the’s anatomy prior to the
procedureprocedure
Donor Rule #1Donor Rule #1
 Do not hurt the donorDo not hurt the donor
 See Rule #2See Rule #2
SafetySafety
87

88. Living Donor BiliaryLiving Donor Biliary
TechniqueTechnique
1.1. Demonstrate anatomy prior to ORDemonstrate anatomy prior to OR
2.2. Confirm anatomy with an on tableConfirm anatomy with an on table
cholangiogramcholangiogram
3.3. Exclude right to left cross overExclude right to left cross over
4.4. Perform a duct to duct anastomosisPerform a duct to duct anastomosis
5.5. Utilize a t-tube for post operative studies andUtilize a t-tube for post operative studies and
drainagedrainage
88

89. Picture of on table cholangiogram priorPicture of on table cholangiogram prior
to splittingto splitting
89

90. 90

91. 91

92. 92

93. 93

94. NYU Donor ComplicationsNYU Donor Complications
 7 Bile leaks requiring intervention7 Bile leaks requiring intervention
 1 non-occlusive PV thrombus1 non-occlusive PV thrombus
 3 peripheral neuropathies3 peripheral neuropathies
 1 pleural effusion drained1 pleural effusion drained
 5 Required blood transfusions5 Required blood transfusions
 2 late laparotomies for SBO2 late laparotomies for SBO
94

95. NYU Recipient BiliaryNYU Recipient Biliary
ComplicationsComplications
 100 right lobectomies100 right lobectomies
 8 patients experienced early biliary complications8 patients experienced early biliary complications
 4 leaks4 leaks
 2 - ERCP and internal stent; 2 - JP drainage2 - ERCP and internal stent; 2 - JP drainage
 1 stricture (following a leak treated by ERCP1 stricture (following a leak treated by ERCP
and internal stent)and internal stent)
 Endoscopic dilationEndoscopic dilation
 13 patients experienced late biliary complications13 patients experienced late biliary complications
 All requiring PTC and DilationAll requiring PTC and Dilation
95

96. Comparative Living Donor LiverComparative Living Donor Liver
Transplant Survival RatesTransplant Survival Rates
Survival CategoriesSurvival Categories
NYUNYU
MedicalMedical
CenterCenter
NationalNational
AverageAverage
DifferenceDifference
Patient SurvivalPatient Survival 91%91% 86.5%86.5% + 4.5%+ 4.5%
Graft SurvivalGraft Survival 88.4%88.4% 80.6%80.6% + 7.8%+ 7.8%
96

97. ResultsResults
97

98. Extracorporeal Liver Assist Device
(ELAD)
98

99. Extracorporeal Liver Assist Device
(ELAD)
99

100. 100