strategies for maximizing outcomes in liver transplantation james d. eason, m.d. chief of...
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Strategies for Maximizing Outcomes in Liver Transplantation
James D. Eason, M.D.Chief of Transplantation / Professor of
SurgeryUniversity of Tennessee / Methodist
Transplant Institute
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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.
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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
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ProblemsExtended Criteria donors
AgeSteatosisDCD
Ischemia Reperfusion InjuryCold and warm ischemiaCell Death over time
ImmunosupressionMinimizing adverse events
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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
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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
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Ischemia-Reperfusion
HTK - Low viscosityBuffered- minimize drop in pHBiliary protectiveEndothelial protective
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Timing is Everything!Cold Ischemic Time
Usually under 6 hoursAnastomotic time
ReperfusionArterialization
Warm Ischemic time in DCDRapid Cannulation
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ImmunosuppressionRATG Induction
May decrease immune contribution to ischemia-reperfusion
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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
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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)
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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
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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
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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
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DCD protocol
Staff surgeon – experience mattersHTKMinimize times
WITCannulationCIT arterialization
Donor selectionProper recipient selection
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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
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Immunosuppression (continued)
Tacrolimus target level
Day 7-12 weeks 6-812-24 weeks 3-56-12 months 3After 12 months 1-3
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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
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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)
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Tacrolimus levels
Day 7 1 month 3 months 6 months One year
6.4 7.2 7.4 7.1 5.8
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Sirolimus
40 patients started on primary sirolimus therapy within 15 days
25 additional patients converted after 30 days
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Minimal Immunosuppression
Single agentTacrolimusSirolimus
Continue weaning to lowest levels
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Maximizing Outcomes
Control controllable factorsIschemic time
Preservation solution- HTKProper selection/ matching ofdonor –
recipientMinimize immunosuppression to
avoid complications
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Conclusion
Excellent outcomes that exceed expected survival can be achieved
with HTK preservation when performed by experienced surgeons
under controlled circumstances