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, 20131

2

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)

Transplants

3

Causes of Death in 262 Causes of Death in 262 DonorsDonors

5

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

New York Organ Donor New York Organ Donor NetworkNetwork

4

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

Doctors Confirm West Nile in a 4th Doctors Confirm West Nile in a 4th Transplant PatientTransplant Patient

Doctors have confirmed that a woman in Florida is the fourth Doctors have confirmed that a woman in Florida is the fourth person to have contracted West Nile virus after receiving an person to have contracted West Nile virus after receiving an organ transplanted from a single donor who had the virus, a organ transplanted from a single donor who had the virus, a federal health official said last night.federal health official said last night.

Finding the virus in all four organ recipients "very strongly Finding the virus in all four organ recipients "very strongly suggestssuggests”” that the disease was transmitted by the organs that the disease was transmitted by the organs rather than by mosquito bites, said the official, Dr. Lyle rather than by mosquito bites, said the official, Dr. Lyle Petersen, a West Nile expert at the Centers for Disease Petersen, a West Nile expert at the Centers for Disease Control and Prevention.Control and Prevention.

--- --- The New York TimesThe New York Times

6

6

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

West Nile VirusWest Nile VirusApproximate Geographic Range in 1998Approximate Geographic Range in 1998

8

9

2005

• 2,949 cases

• 628 counties

• 42 states

10

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

Tem pCurveNeurologic

Neurologic

Temp Curve

OLTX T 105° Weakness

Seizures Flaccid Paralysis

68 days

expired

PATIENT COURSE

OMR-IgG-am IgG

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

Tumor ConveyanceTumor Conveyance

““Teen Organ Donor's Gift Turns Teen Organ Donor's Gift Turns TragicTragic””11

““Transmission of Anaplastic Large Transmission of Anaplastic Large Cell Lymphoma via Organ Cell Lymphoma via Organ

Donation After Cardiac DeathDonation After Cardiac Death””22

1. SAG HARBOR, N.Y., April 1, 2008, Nancy Cordes, CBS News Correspondent2. 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

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

Donor-Derived Disease Transmission Donor-Derived Disease Transmission Events in the United States: Data Events in the United States: Data

ReviewedReviewedby the OPTN/UNOS Disease by the OPTN/UNOS Disease

TransmissionTransmissionAdvisory 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

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.

““The liver does The liver does not undergo not undergo senescence.senescence.””

-Hans Popper, MD-Hans Popper, MD

7

The Successful Use of The Successful Use of Older Donors for Liver Older Donors for Liver

TransplantationTransplantationL. Teperman, L. Podesta, L. Mieles, T. L. Teperman, L. Podesta, L. Mieles, T.

Starzl JAMA 1989; 262:2837Starzl JAMA 1989; 262:2837

8

Donor FactorsDonor Factors

Age BarrierAge Barrier > 80 Years> 80 Years Fat Content:Fat Content: macro vs. macro vs.

micromicro Length of stay Length of stay > 10 days> 10 days HypernatremiaHypernatremia

19

Expanded Criteria Expanded Criteria DonorDonor

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

19961991

Obesity Trends* Among U.S. AdultsBRFSS, 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

Obesity Trends* Among U.S. AdultsBRFSS, 2011

http://feww.files.wordpress.com/2011/07/obesity-2011-feww1.png22

23

Retransplant Rates in Retransplant Rates in Region vs. the USRegion vs. 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

Ret

rans

plan

t Rat

es (

%)

NYU

5%

24

Utility vs. EquityUtility vs. Equity

12

Old Allocation SystemOld Allocation SystemChild-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 >10cholestatic liver diseases:Bilirubin (mg/dL)*

16

26

Problems with CTP ScoreProblems with CTP Score

Limited number Limited number ofof categories categories Limited Limited discriminating abilitydiscriminating ability Uses Uses subjective parameters subjective parameters -- gaming gaming Laboratory Laboratory variabilityvariability (protime, (protime,

albumin)albumin) Never validatedNever validated CreatinineCreatinine not included not included

18

27

Q: What is Q: What is MELD?MELD?

A: Disease Severity ScoreA: Disease Severity Score

90% Survival Probability on the 90% Survival Probability on the waitlistwaitlist

VariablesVariables BilirubinBilirubin CreatinineCreatinine INRINR

““ CHANGE REAGENTCHANGE REAGENT”” Liver disease etiology (deleted)Liver disease etiology (deleted)

MELD MODEL:MELD MODEL: Predicts Survival in TIPS Patients

21

?

29

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 x MELD = (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

HCC: Extra CreditHCC: Extra Credit

Patients meeting criteria receive Patients meeting criteria receive 2222 points. points.

After a three-month reevaluation After a three-month reevaluation patients receive additional points.patients receive additional points.

Thereafter they receive additional Thereafter they receive additional points every three months.points every three months.

31

Indications for Indications for TransplantationTransplantation

NYUC Txps 2007 32

Hepatitis C Tumor Hepatitis C Tumor BurdenBurden

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)

25

33

Lewis Teperman, M.D.

Abdominal Organ Cluster Abdominal Organ Cluster Transplantation for the Transplantation for the

Treatment of Upper Abdominal Treatment of Upper Abdominal MalignanciesMalignancies

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

35

36

OLT Survival Milan OLT Survival Milan CriteriaCriteria

60 1812 3024 4236 48

20

0

40

60

100

80

Months

Pro

bab

ilit

y (%

)

Mazzaferro, V. N Engl J Med 1996

37

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 Are 6 cm lesions really more deadly

than 5 ?than 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

HCC Recurrence after HCC Recurrence after OLTOLT

5040 6010 3020

.2

0

.4

.6

1.

.8

Months

Recu

rren

ce

.3

.5

.7

.9

.1No Vascular

Invasion

Vascular Invasion

Hemming, A. Ann Surg 2001

0

39

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

Strategies for Long Strategies for Long Waiting TimeWaiting Time

TACE TACE

Living Donor TransplantLiving Donor Transplant

41

Chemoembolization Chemoembolization (CE) for HCC(CE) for HCC

Femoral artery CatheterizationFemoral artery Catheterization 3 Elements3 Elements

LipiodolLipiodol Chemotherapeutic agent(adriamycin, Chemotherapeutic agent(adriamycin,

cisplatinum)cisplatinum) Embolizing Agent(Gelform, Avitene)Embolizing Agent(Gelform, Avitene)

Selective hepatic arterial localizationSelective hepatic arterial localization ““KillKill”” Rates Rates Without significant complicationsWithout significant complications*Neo adjuvant: Thalidomide (-)*Neo adjuvant: Thalidomide (-)

(+) NEXAVAR MULTI-CENTER(+) NEXAVAR MULTI-CENTER TRIAL 2012TRIAL 2012

36

42

43

44

Chemoembolization Chemoembolization Random Effects ModelRandom Effects Model

6395

503

807379

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

Patient Survival after liver Patient Survival after liver transplantation:transplantation:

Benign vs. Malignant diseaseBenign vs. Malignant disease

Months after transplantation

33

46

TRANSPLANTATION FOR TRANSPLANTATION FOR HEP B HBIG TREATMENTHEP B HBIG TREATMENT

Months

HBIG HBIG HBIG

31

47

There is NO consensus on There is NO consensus on optimal duration of HBIG, dose, optimal duration of HBIG, dose, or mode of administration.or mode of administration.

-- Lewis TepermanLewis Teperman 10/15/200610/15/2006

48

Viral DNA Chain Viral DNA Chain TerminatorsTerminators

GanciclovirGanciclovir FamciclovirFamciclovir LamivudineLamivudine AdefovirAdefovir EntecevirEntecevir TenofovirTenofovir EmtricitabineEmtricitabine

28

49

A Randomized Trial of HBIG A Randomized Trial of HBIG Withdrawal Using Withdrawal Using

Emtricitabine/Tenofovir DF Emtricitabine/Tenofovir DF in Post-Liver Transplant in Post-Liver Transplant

RecipientsRecipients 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 and F RousseauRousseau88

11The 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; 22Emory Healthcare, Atlanta, GA; Emory Healthcare, Atlanta, GA;

33Cedars-Sinai Medical Center, Los Angeles, CA; Cedars-Sinai Medical Center, Los Angeles, CA; 44Recanati/Miller Transplantation Institute, Recanati/Miller Transplantation Institute, Mount Sinai Hospital, New York, NY; Mount Sinai Hospital, New York, NY; 55California Pacific Medical Center, San Francisco, CA;California Pacific Medical Center, San Francisco, CA;

66Mayo Clinic Jacksonville, Jacksonville, FL; Mayo Clinic Jacksonville, Jacksonville, FL; 7 7 Schiff Liver Institute,Schiff Liver Institute, University of Miami,University of Miami,Miller School of Medicine, Miami, FL; Miller School of Medicine, Miami, FL; 88Gilead Sciences Inc., Durham, NCGilead Sciences Inc., Durham, NC

BackgroundBackground

HBIG prophylaxis is routinely prescribed to HBIG prophylaxis is routinely prescribed to prevent HBV recurrence post-orthotopic prevent HBV recurrence post-orthotopic liver transplantation (OLT) liver transplantation (OLT)

HBIG prevents recurrence by HBIG prevents recurrence by neutralizingneutralizing HBsAgHBsAg

Long-term prophylaxis with HBIG is Long-term prophylaxis with HBIG is inconvenient and expensive, but is the inconvenient and expensive, but is the mainstay of post-transplant therapy.mainstay of post-transplant therapy.

51

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

AimAim

This ongoing randomized study (Study 107) This ongoing randomized study (Study 107) evaluates the safety and evaluates the safety and efficacy of TVD efficacy of TVD with/without HBIG with/without HBIG in preventing recurrence in preventing recurrence of CHB post OLTof CHB post OLT

The aim of this The aim of this interim analysis interim analysis is to is to evaluate the efficacy, safety and tolerability evaluate the efficacy, safety and tolerability of TVD in this populationof TVD in this population

53

Patient Disposition

ScreenedN=51

EnrolledN=40

Randomized at Week 24N=37

Discontinued N=3

TVD+HBIGN=19

TVDN=18

Completed Week 72 N=15 Completed Week 96 N=11

Completed Week 72 N=14Completed Week 96 N=12

Discontinued N=1Death N=1

Discontinued N=1

Virologic OutcomesVirologic Outcomes

No detectable HBV DNA (169 No 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

Hepatitis CHepatitis C

Most common indication for Most common indication for transplantation 25 - 45%transplantation 25 - 45% 95% of recipients persist with antibody 95% of recipients persist with antibody

to Cto C At least 50% develop active hepatitis on At least 50% develop active hepatitis on

biopsybiopsy It is unknown how many progress to a It is unknown how many progress to a

chronic statechronic state

56

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

Baylor Zenapax Trial

Steroid SparingI 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

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

““The challenge of The challenge of transplant surgery is transplant surgery is

NOT the surgeryNOT the surgery””

39

60

40

61

Immunologic Armamentarium Immunologic Armamentarium (Arsenal)(Arsenal)

Vietnam ConflictVietnam Conflict Imuran Imuran - - Ground TroopsGround Troops Steroids Steroids - - Light ArtilleryLight Artillery

Cold WarCold War Cyclosporine Cyclosporine - - F16F16 Okt3Okt3 - - ““TacticalTactical”” warhead / cruise missile warhead / cruise missile

Desert StormDesert Storm PrografPrograf - - Smart BombSmart Bomb Neoral Neoral - - 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 - Modified Osprey

TransportTransport

War on TerrorWar on Terror ThymoglobulinThymoglobulin - - Biologic Weapon Biologic Weapon Campath Campath - Modified Biologic - Modified Biologic

WeaponWeapon

42

62

Risk of Chronic Renal Risk of Chronic Renal FailureFailure

A 15-year experience at Baylor A 15-year experience at Baylor Medical Center found that at 13 Medical Center found that at 13 years after liver transplantationyears after liver transplantation Incidence of severe renal Incidence of severe renal

dysfunction of 18.1%dysfunction of 18.1% Chronic renal failure in 8.6% of Chronic renal failure in 8.6% of

patientspatients ESRD in 9.5% of patientsESRD in 9.5% of patients

Gonwa TA et al. Transplantation 2001;72:1934-1939.

63

Risk of Chronic Renal Risk of Chronic Renal FailureFailure

Number at RiskNumber at RiskHeart-Heart-lunglung 576576 375375 295295 219219 194194 156156 133133 107107 7272 4646 3030

HeartHeart 24,024,01414

19,8819,8855

17,2317,2388

14,6814,6877

12,3412,3411

10,0210,0222

7,9977,997 6,1046,104 4,5264,526 3,0963,096 1,9911,991

IntestiIntestinene 228228 152152 110110 8484 5757 3333 2323 1313 88 55 55

LiverLiver 36,836,84949

28,4928,4955

24,0424,0411

19,5019,5088

15,7215,7244

12,5612,5644

9,8449,844 7,3457,345 5,2925,292 3,6143,614 2,2612,261

LungLung 7,647,6433

5,6335,633 4,3164,316 3,1843,184 2,3272,327 1,6291,629 1,1361,136 745745 468468 258258 133133Ojo AO, et al. N Engl J Med 2003;349:931-40.

Months since Transplantation

Cu

mu

lati

ve

In

cid

en

ce

of

Ch

ron

ic R

en

al

Fa

ilu

re

0.35

0.30

0.25

0.20

0.15

0.10

0.05

0.000 12 24 12010884 967236 48 60

LungIntestine

Heart

Liver

Heart–lung

64

Calcineurin inhibitor-Calcineurin inhibitor-free maintenance with free maintenance with

mycophenolate mycophenolate mofetil/sirolimus in mofetil/sirolimus in

liver transplant liver transplant recipients: Save-the-recipients: Save-the-

Nephron TrialNephron 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. and J. RobertsRoberts1010

11New York University School of Medicine, New York, New York; New York University School of Medicine, New York, New York; 22Henry Ford Health Systems, Detroit, Michigan; Henry Ford Health Systems, Detroit, Michigan; 33Integris Baptist Medical Center, Oklahoma City, Oklahoma; Integris Baptist Medical Center, Oklahoma City, Oklahoma; 44University of Southern California, Los Angeles, University of Southern California, Los Angeles,

California; California; 55London Health Sciences Hospital, London, Ontario, Canada; London Health Sciences Hospital, London, Ontario, Canada; 66Scripps Green Hospital, La Jolla, Scripps Green Hospital, La Jolla, California; California; 77University of Medicine and Dentistry of New Jersey, Newark, New Jersey; University of Medicine and Dentistry of New Jersey, Newark, New Jersey; 88Saint LukeSaint Luke’’s Episcopal s Episcopal

Hospital, Houston, Texas; Hospital, Houston, Texas; 99Genentech, South San Francisco, California; Genentech, South San Francisco, California; 1010University of California, San Francisco, University of California, San Francisco, CaliforniaCalifornia

 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

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

WWEEEEKKSS

PPOOSSTT--TTXX

2 years2 years

ScreeningScreening Enrollment

66

Mean %Mean % Increase in Increase in Calculated GFRCalculated GFR

Baseline to Month 6Baseline to Month 6

N = 8455.81.91.9

N = 8650.61.91.9

0

5

10

15

20

25

30

35

Mea

n P

erce

nt

Incr

ease

(±S

EM

)

MMF/SRL

MMF/CNI

3.2

40

Baseline GFR SEM (mL/min)

29.2

67

ConclusionsConclusions At least At least 62%62% of individuals are able to of individuals are able to

toleratetolerate a maintenance regimen of MMF/SRL a maintenance regimen of MMF/SRL and will benefitand will benefit

In the short term, In the short term, MMF/SRL improvesMMF/SRL improves renal renal functionfunction when compared to CNI-containing when compared to CNI-containing regimens regimens

The addition of The addition of lipid-lowering agentslipid-lowering agents may be may be necessary in patients receiving MMF/SRLnecessary in patients receiving MMF/SRL

Complete follow-up of the 294Complete follow-up of the 294 patients will patients will provide a more provide a more statistically statistically robust conclusion robust conclusion about the long-term effect of this regimenabout the long-term effect of this regimen

68

Donor and NYU Donor and NYU TimelineTimeline

1999 Living Donation (Right Lobe Adult)

1997 Split Livers (peds) (Adult)

1990 Living Donation Lateral Segment (peds)

1988 Reduced Sized Grafts (peds)

52

1963 University Hospital Built

1965 1st Successful Liver Transplant

New Transplant Regulations

69

DONOR RISKSDONOR RISKS

New York Newsday, March 13, 2002

55

70

Transplant Chief at Mt. Sinai Quits Transplant Chief at Mt. Sinai Quits Post in Wake of InquiryPost in Wake of Inquiry

A week after Mount Sinai Medical Center was A week after Mount Sinai Medical Center was cited by the state for dozens of serious cited by the state for dozens of serious violations, the chief of its liver transplant violations, the chief of its liver transplant center has stepped down and the entire center has stepped down and the entire program will be restructured, hospital officials program will be restructured, hospital officials announced yesterday.announced yesterday.

--- --- The New York TimesThe New York Times

56

71

Summer of 2010Summer of 2010

2 Recent U.S. Deaths2 Recent U.S. Deaths ColoradoColorado MassachusettsMassachusetts

72

New York State New York State Report of the Subcommittee on Report of the Subcommittee on Donor Perioperative Care and Donor Perioperative Care and

Facility ReportFacility Report

Lewis Teperman M.D., Chair

73

New Preoperative Care New Preoperative Care RegsRegs

1.1. Psychiatric EvaluationPsychiatric Evaluation2.2. Bank BloodBank Blood3.3. 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 care1.1. ICU (days 0 - 1)ICU (days 0 - 1) 1 Nurse / 2 Patients1 Nurse / 2 Patients2.2. Floor Floor 1 Nurse / 4 patients1 Nurse / 4 patients3.3. Residents Residents (pgy2) / NP(pgy2) / NP 24/724/7

5.5. RegistryRegistry1.1. OutcomeOutcome

* Qualified74

Living Donor RecipientsLiving Donor Recipients

InclusionInclusion Listed with UNOS and must have a Listed with UNOS and must have a

significant complication of liver diseasesignificant complication 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

HCC: Extra CreditHCC: Extra Credit

Is Living Donation Is Living Donation justified?justified?

Patients meeting criteria receive Patients meeting criteria receive 2222 points. points.

After a three-month reevaluation After a three-month reevaluation patients receive additional points.patients receive additional points.

Thereafter they receive additional Thereafter they receive additional points every three months.points every three months.

76

Hepatoma Predictor Hepatoma 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)

Recip

ien

t li

fe e

xp

ecta

ncy

(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 2001

77

$$

No Selling of OrgansNo Selling of Organs57

78

Donor Candidacy Donor 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

58

79

MELD Score Comparison of MELD Score Comparison of Cadaveric vs. Living Related Cadaveric vs. Living Related

DonorsDonors

Average Living Donor MELD Score:Average Living Donor MELD Score:

17.417.4

Average Cadaveric MELD Score:Average Cadaveric MELD Score:

3232

66

80

60

81

1% Rule1% Rule

70kg recipient needs a 700cc liver 70kg recipient needs a 700cc liver graft (1% GRWR)graft (1% GRWR)

1% mortality1% mortality(Actually ~0.05% but over (Actually ~0.05% but over emphasize to define risk)emphasize to define risk)

65

82

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 Left hepatic resections will

have more complicationshave more complications

64

83

Living DonorsLiving DonorsWhat the Surgeon Needs to Know:What the Surgeon Needs to Know:

Liver ParenchymaLiver Parenchyma Right lobe volumeRight lobe volume Exclude fatty Exclude fatty

infiltrationinfiltration Characterize Characterize

lesionslesions Hepatic arteriesHepatic arteries

Arterial variantsArterial variants RHA originRHA origin

Portal veinsPortal veins PV variants, RPV PV variants, RPV

originorigin

Hepatic veinsHepatic veins RHV lengthRHV length MHV branches to MHV branches to

right loberight lobe Inferior accessory Inferior accessory

HVHV Biliary ductsBiliary ducts

Biliary variantsBiliary variants Rt lateral duct Rt lateral duct

originorigin84

Volumetric MR Volumetric MR CholangiographyCholangiography

Lee VS, Teperman L, et Al. AJR, 2001.85

CT CholangiographyCT Cholangiography

Higher Spatial Higher Spatial Resolution than Resolution than MRMR

Shorter Exam Shorter Exam TimeTime

Radiation DoseRadiation Dose Contrast AgentContrast Agent

86

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 Do not hurt the

donordonor See Rule #2See Rule #2

63 SafetySafety

87

Living Donor Biliary Living Donor Biliary TechniqueTechnique

1.1. Demonstrate anatomy prior to ORDemonstrate anatomy prior to OR2.2. Confirm anatomy with an on table Confirm anatomy with an on table

cholangiogramcholangiogram3.3. Exclude right to left cross overExclude right to left cross over4.4. Perform a duct to duct anastomosisPerform a duct to duct anastomosis5.5. Utilize a t-tube for post operative Utilize a t-tube for post operative

studies and drainagestudies and drainage

88

Picture of on table cholangiogram prior Picture of on table cholangiogram prior to splittingto splitting

89

69

90

70

91

71

92

93

NYU Donor NYU Donor ComplicationsComplications

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

77

94

NYU Recipient Biliary NYU Recipient Biliary ComplicationsComplications

100 right lobectomies100 right lobectomies 8 patients experienced early biliary 8 patients experienced early biliary

complicationscomplications 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 ERCP 1 stricture (following a leak treated by ERCP

and internal stent)and internal stent) Endoscopic dilationEndoscopic dilation

13 patients experienced late biliary 13 patients experienced late biliary complicationscomplications All requiring PTC and DilationAll requiring PTC and Dilation

95

Comparative Living Donor Comparative Living Donor Liver Transplant Survival Liver Transplant Survival

RatesRates

Survival Survival CategoriesCategories

NYU NYU Medical Medical CenterCenter

National National 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

ResultsResults78

97

Extracorporeal Liver Assist Device (ELAD)

98

Extracorporeal Liver Assist Device (ELAD)

99

100