Disclosures Normothermic Machine Liver Perfusion I have nothing to disclose Garrett R. Roll, MD Assistant Professor of Surgery Overview Define normothermic machine liver perfusion (NMLP) Show device examples Review the available data What is NMLP A method of liver preservation Device with a closed circuit filled with PRBCs Maintains the liver at 37 degrees C Has an oxygenator Nutrients, medications, etc. near-physiologic conditions Why are 20% of livers discarded? Discuss the potential to improve liver utilization 1
At the donor hospital Cold Ischemia Time Cold ischemia time is a very injurious time for liver allografts 45 minutes NMLP reduces cold ischemia time from 6-12 hours down to 45 min Tolerated by livers from young DBD donors without steatosis Not tolerated by livers from older, steatotic livers and livers from DCD NMLP devices First human data: Safety study LiverAssist OrganOx Metra Transmedics Safety study OrganOx Metra device 20 patients 3 centers: Oxford, Birmingham and Kings 10 DBD and 10 DCD No cold storage arm What we learned: 100 % survival (safe) Minimal reperfusion syndrome Primary outcome: 30-day survival Ravikumar et al, AJT 2016 2
OrganOx Metra: Randomized trial Preventing EAD and PNF COPE Consortium 220 patients 7 centers (UK, Germany, Spain, Belgium) Randomized to NMLP vs cold storage Enrollment completed EAD and PNF Life-threatening complications Very difficult to treat Require lots of resources Livers from marginal donors are the highest risk for these complications Awaiting the results Peak AST, graft survival, biliary complications the reason many livers are not utilized Worsening donor pool Ideal: <60 yrs old, BMI < 30, no extensive Tob or HTN Worsening donor pool We know that if these marginal livers don t fail from PNF or biliary complications they work very well for a very long time 3
Utilization Another way to see discard? UNOS recently reported that only 6,312 of 8,144 of livers that were procured were transplanted Countless more potential donors were never approached Percentage 100 90 80 70 60 50 40 Potential DCD donors (2013-2014) % of all organs 83% PNF concerns Trans Why? The risk of primary non function 30 20 10 0 Kidney Liver Pancreas Lungs Organs from actual DCD donors Donor age criteria met Consent for organ donation Organs offered for donation Organs retrieved for transplant 28% 8% 6% Organs transplanted Can NMLP reduce PNF? We think PNF is caused by: Glycogen depletion, ATP depletion, anerobic metabolism during storage Severe ischemia reperfusion injury NMLP reduces ischemia time by 90% NMLP restores glycogen in the liver YES!!! Ex-situ monitoring of liver function Objective, real-time Flow measurements Bile production Biochemical analysis Lactate ph glucose And, NMLP allows you to test for PNF - VIBILITY TESTING Reduce lactate under 2 mmol/l after 2 hours of NMLP 4
First example of viability testing Patient with consented to undergo transplant with a liver turned down by all other UK centers First example in humans Donor: 29M DCD with BMI 24, Donor WIT: 49min (from SBP<50) At a remote hospital/long travel time Brought it back to Birmingham and put it on the LiverAssist High risk donor > turned down by all > viability testing > transplant 6 livers turned down by all UK centers Donors DCD with 109 min WIT DCD with BMI of 45 DCD with DRI >3 Transplanted 5 of 6 100% immediate graft function Only 1 required CVVH No biliary complications 5
The real benefit of NMLP : Identifies PNF prior to putting the recipient at risk Could have a profound impact on liver utilization Estimates: 20-40% increase in utilization Watson et al, Ann Surg 2016 The potential of NMLP Not to replace cold storage of normal livers What needs to be studied? PNF Randomized Cold vs NMLP Turned down by all Transplanted NMLP Outcomes Transplant or discard 6
Cost Challenges Logitisics at the donor hospital and transportation Designing a the clinical trial that will show reduced rates of PNF while increasing utilization is very difficult Somehow allow the data to catch up to the experience described by early adaptors of this new technology Conclusions Cold storage is a very injurious time for marginal livers NMLP improves early liver function after transplant and appears to reduce biliary complications NMLP reduces cold storage from 6-12 hours to 45 min Real value is viability testing without putting the patient at risk Don t need to compare NMLP to cold storage of normal livers, but compare it to discard of marginal livers Consider the limitations of structuring human clinical trials to demonstrate PNF and organ discard 7