9/29/2016 � Disclosures Normothermic Machine I have nothing to disclose Liver Perfusion Garrett R. Roll, MD Assistant Professor of Surgery What is NMLP Overview A method of liver preservation Define normothermic machine liver perfusion (NMLP) Device with a closed circuit filled with PRBCs Show device examples Maintains the liver at 37 degrees C Has an oxygenator Nutrients, medications, etc. Review the available data …near-physiologic conditions Why are 20% of livers discarded? Discuss the potential to improve liver utilization 1 �
9/29/2016 � 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 Safety study LiverAssist OrganOx Metra device 20 patients OrganOx Metra 3 centers: Oxford, Birmingham and Kings 10 DBD and 10 DCD Transmedics No cold storage arm What we learned: 100 % survival (safe) Minimal reperfusion syndrome Primary outcome: 30-day survival Ravikumar et al, AJT 2016 2 �
9/29/2016 � OrganOx Metra: Randomized trial Preventing EAD and PNF COPE Consortium EAD and PNF Life-threatening complications Very difficult to treat 220 patients Require lots of resources 7 centers (UK, Germany, Spain, Belgium) Randomized to NMLP vs cold storage Livers from marginal donors are the highest risk for these complications Enrollment completed Awaiting the results …the reason many livers are not utilized Peak AST, graft survival, biliary complications Worsening donor pool Worsening donor pool Ideal: <60 yrs old, BMI < 30, no extensive Tob or HTN 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 �
9/29/2016 � Utilization Another way to see discard? Potential DCD donors (2013-2014) 1 April 2013 – 31 March 2014 UNOS recently reported that only 6,312 of 8,144 of Trans 100 % of all livers that were procured were transplanted organs 90 83% 80 PNF concerns 70 Countless more potential donors were never approached 60 Percentage 50 40 30 28% Why…? 20 The risk of primary non function 10 8% Kidney Liver Pancreas Lungs 6% 0 Organs from Donor age Consent for Organs offered Organs retrieved Organs actual DCD criteria met organ donation for donation for transplant transplanted donors Can NMLP reduce PNF? Viability testing Ex-situ monitoring of liver function We think PNF is caused by: Glycogen depletion, ATP depletion, anerobic metabolism during storage Objective, real-time Severe ischemia reperfusion injury Flow measurements Bile production NMLP reduces ischemia time by 90% YES !!! Biochemical analysis NMLP restores glycogen in the liver Lactate pH glucose Reduce lactate under 2 mmol/L after 2 hours of NMLP And, NMLP allows you to test for PNF - VIBILITY TESTING 4 �
9/29/2016 � First example of viability First example in humans testing Viability testing Patient with consented to undergo transplant with a liver turned down by all other UK centers 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 Viability testing Viability testing 6 livers turned down by all UK centers Transplanted 5 of 6 Donors… 100% immediate graft function DCD with 109 min WIT Only 1 required CVVH DCD with BMI of 45 DCD with DRI >3 No biliary complications 5 �
9/29/2016 � Viability testing The real benefit of NMLP Viability testing: 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 What needs to be studied? PNF The potential of NMLP Not to replace cold storage of normal livers Randomized Turned down by all Cold vs NMLP Transplanted NMLP Viability testing Transplant or Outcomes discard 6 �
9/29/2016 � Challenges Conclusions Cold storage is a very injurious time for marginal livers Cost NMLP improves early liver function after transplant and appears to reduce biliary complications Logitisics at the donor hospital and transportation NMLP reduces cold storage from 6-12 hours to 45 min Designing a the clinical trial that will show reduced Real value is viability testing without putting the rates of PNF while increasing utilization is very difficult patient at risk Don’t need to compare NMLP to cold storage of normal Somehow allow the data to catch up to the experience livers, but compare it to discard of marginal livers described by early adaptors of this new technology Consider the limitations of structuring human clinical trials to demonstrate PNF and organ discard 7 �
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