Strategies for Maximizing Outcomes in Liver Transplantation

1
Strategies for Maximizing Outcomes in Liver
Transplantation

• James D. Eason, M.D.
• Chief of Transplantation / Professor of Surgery
• University of Tennessee / Methodist Transplant
  Institute

2
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 Feb9(2)286-93.

3
Results

• All deceased donor transplants (n 4755 HTK and
  12 673 UW)
• HR 1.14 (1.051.23) p 0.002
• Donor after cardiac death (n 254 HTK and 575
  UW)
• HR1.44 (1.051.97) p 0.025

4
Problems

• Extended Criteria donors
• Age
• Steatosis
• DCD
• Ischemia Reperfusion Injury
• Cold and warm ischemia
• Cell Death over time
• Immunosupression
• Minimizing adverse events

5
UT Experience

• 120 Liver Transplants in 2008
• 9th Largest in US
• 401 Cadaveric OLT over 40 months
• 24 DCD
• HTK perfusion in 90 of donors
• RATG induction
• Steroid-free immunosuppression

6
National Results
Patient 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
7
Ischemia-Reperfusion

• HTK -
• Low viscosity
• Buffered- minimize drop in pH
• Biliary protective
• Endothelial protective

8
Timing is Everything!

• Cold Ischemic Time
• Usually under 6 hours
• Anastomotic time
• Reperfusion
• Arterialization
• Warm Ischemic time in DCD
• Rapid Cannulation

9
Immunosuppression

• RATG Induction
• May decrease immune contribution to
  ischemia-reperfusion

10
Results

• 9th largest program in 2008
• 401 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

11
A Matter of Time

• Warm Ischemic Time (anastomotic) 36.8 11.9
  minutes
• Cold Ischemic Time 5.7 2.2 hours
• Arterialization - 60 minutes
• Mean operative time 4 hours (2.1 6)

12
DCD results

• 24 DCD OLT over 3 years
• Mean F/U 450 days
• 20 patients gt 1 year
• 91 one -year patient survival
• 2 deaths within one year
• 1sepsis, 1 PNF
• 1 death at 13 months - heart failure
• 2 patients with intrahepatic strictures two years
  post-transplant

13
DCD

• MELD -median 18 (15-22)
• Donor age mean- 35years (15-52)
• Cannulation time 2minutes
• Warm Ischemic time - (7-42 minutes)pressure / O2
  sat lt 80
• Cold ischemic time - 5.47 hours (2.3 - 8.3)
• Anastomotic time - mean 32 minutes

14
DCD deaths
15
DCD protocol

• Staff surgeon experience matters
• HTK
• Minimize times
• WIT
• Cannulation
• CIT
• arterialization
• Donor selection
• Proper recipient selection

16
Immunosuppression Protocol

• RATG 1.5 mg/kg in anhepatic phase and POD 2
  total 3mg/kg
• Premedication -500 mg methylprednisolone, 500 mg
  acetominophen and 25mg diphenhydramine
• MMF 1gram BID on Day 1
• Tacrolimus begun on day 2 or when serum
  creatinine fell below 2mg/dl
• Primary sirolimus if serum creatinine gt 2.5 or
  oliguric by Day 7

17
Immunosuppression (continued)

• Tacrolimus target level
• Day 7-12 weeks 6-8
• 12-24 weeks 3-5
• 6-12 months 3
• After 12 months 1-3

18
Tacrolimus Initiation

• Mean 3.5 1.8 days
• Range 2 12 days
• 27 patients started day 4 12
• 7 subsequently converted to sirolimus
• Mean tacrolimus levels
• Day 7- 4.5
• Day 30 - 6

19
Serum Creatinine Liver Transplant Recipients
only (n 101)
P lt 0.001 (for all time points)
Time Post-Transplant plt .001 for all time points
from pretransplant
20
Tacrolimus levels
Day 7 1 month 3 months 6 months One year
6.4 7.2 7.4 7.1 5.8
21
Sirolimus

• 40 patients started on primary sirolimus therapy
  within 15 days
• 25 additional patients converted after 30 days

22
Minimal Immunosuppression

• Single agent
• Tacrolimus
• Sirolimus
• Continue weaning to lowest levels

23
Maximizing Outcomes

• Control controllable factors
• Ischemic time
• Preservation solution- HTK
• Proper selection/ matching ofdonor recipient
• Minimize immunosuppression to avoid complications

24
Conclusion

• Excellent outcomes that exceed expected survival
  can be achieved with HTK preservation when
  performed by experienced surgeons under
  controlled circumstances