Strategies for Maximizing Outcomes in Liver Transplantation

James D. Eason, M.D.Chief of Transplantation / Professor of

SurgeryUniversity of Tennessee / Methodist

Transplant Institute

Recent Publications

(HTK) is associated with reduced graft survival in deceased donor livers, especially those donated after cardiac death.

Stewart ZA, Cameron AM, Singer AL, Montgomery RA, Segev DL. Am J Transplant. 2009 Feb;9(2):286-93.

Results

All deceased donor transplants (n = 4755 HTK and 12 673 UW)HR 1.14 (1.05–1.23) p = 0.002

Donor after cardiac death (n = 254 HTK and 575 UW) HR1.44 (1.05–1.97) p = 0.025

ProblemsExtended Criteria donors

AgeSteatosisDCD

Ischemia Reperfusion InjuryCold and warm ischemiaCell Death over time

ImmunosupressionMinimizing adverse events

UT Experience120 Liver Transplants in 2008

9th Largest in US401 Cadaveric OLT over 40 months

24 DCDHTK perfusion in 90% of donorsRATG induction

Steroid-free immunosuppression

National ResultsPatient Graft

United States 88.34 84.31

University of TN/Methodist

91.0 86.51

Cleveland Clinic 90.09 83.94

Indiana- Clarian 88.33 86.62

Johns Hopkins 79.81 72.41

Ischemia-Reperfusion

HTK - Low viscosityBuffered- minimize drop in pHBiliary protectiveEndothelial protective

Timing is Everything!Cold Ischemic Time

Usually under 6 hoursAnastomotic time

ReperfusionArterialization

Warm Ischemic time in DCDRapid Cannulation

ImmunosuppressionRATG Induction

May decrease immune contribution to ischemia-reperfusion

Results9th largest program in 2008401 adult OLT over 40 months

20 combined liver/kidney

Age at Transplant 52.8 ± 9.42 years

Male Recipient 73.3%Caucasian Recipient 72.4% MELD Score 22 ± 4.89

A Matter of TimeWarm Ischemic Time (anastomotic) 36.8 ±

11.9 minutesCold Ischemic Time 5.7 ± 2.2 hoursArterialization - 60 minutesMean operative time 4 hours (2.1 – 6)

DCD results24 DCD OLT over 3 years

Mean F/U – 450 days20 patients > 1 year

91% one -year patient survival2 deaths within one year1sepsis, 1 PNF

1 death at 13 months - heart failure2 patients with intrahepatic strictures two

years post-transplant

DCDMELD -median 18 (15-22)Donor age mean- 35years (15-52)Cannulation time – 2minutes Warm Ischemic time - (7-42 minutes)pressure

/ O2 sat < 80Cold ischemic time - 5.47 hours (2.3 - 8.3)Anastomotic time - mean 32 minutes

DCD deathsPATIENT CIT

(hours) Anastomotic Time

WIT (minutes)

Other factors

#1 PNF Day 12

6.27 68 minutes 15.24 Recipient 66, multiple surgery

#2 Sepsis Day 40

6.0 28 24 61

#3 Biliary strictures heart failure Day 450

8.0 52 20.44 73 y/o CABG

DCD protocol

Staff surgeon – experience mattersHTKMinimize times

WITCannulationCIT arterialization

Donor selectionProper recipient selection

Immunosuppression ProtocolRATG 1.5 mg/kg in anhepatic phase and

POD 2 – total 3mg/kgPremedication -500 mg methylprednisolone,

500 mg acetominophen and 25mg diphenhydramine

MMF 1gram BID on Day 1Tacrolimus begun on day 2 or when

serum creatinine fell below 2mg/dlPrimary sirolimus if serum creatinine >

2.5 or oliguric by Day 7

Immunosuppression (continued)

Tacrolimus target level

Day 7-12 weeks 6-812-24 weeks 3-56-12 months 3After 12 months 1-3

Tacrolimus InitiationMean 3.5+ 1.8 daysRange 2 – 12 days27 patients started day 4 – 12

7 subsequently converted to sirolimusMean tacrolimus levels

Day 7- 4.5Day 30 - 6

Serum Creatinine Liver Transplant Recipients only (n= 101)

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

Pre-transplant Day 3 Month 1 Month 3 Month 6

Time Post-Transplant p< .001 for all time points from pretransplant

P < 0.001 (for all time points)

Tacrolimus levels

Day 7 1 month 3 months 6 months One year

6.4 7.2 7.4 7.1 5.8

Sirolimus

40 patients started on primary sirolimus therapy within 15 days

25 additional patients converted after 30 days

Minimal Immunosuppression

Single agentTacrolimusSirolimus

Continue weaning to lowest levels

Maximizing Outcomes

Control controllable factorsIschemic time

Preservation solution- HTKProper selection/ matching ofdonor –

recipientMinimize immunosuppression to

avoid complications

Conclusion

Excellent outcomes that exceed expected survival can be achieved

with HTK preservation when performed by experienced surgeons

under controlled circumstances