Disclosures Normothermic Machine I have nothing to disclose Liver - - PowerPoint PPT Presentation

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Normothermic Machine Liver Perfusion

Garrett R. Roll, MD Assistant Professor of Surgery

Disclosures

I have nothing to disclose

Overview

Define normothermic machine liver perfusion (NMLP) Show device examples Review the available data Discuss the potential to improve liver utilization Why are 20% of livers discarded?

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

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At the donor hospital

45 minutes

Cold Ischemia Time

NMLP reduces cold ischemia time from 6-12 hours down to 45 min Cold ischemia time is a very injurious time for liver allografts Tolerated by livers from young DBD donors without steatosis Not tolerated by livers from older, steatotic livers and livers from DCD

NMLP devices

LiverAssist OrganOx Metra Transmedics

First human data: Safety study

Safety study OrganOx Metra device 20 patients 3 centers: Oxford, Birmingham and Kings 10 DBD and 10 DCD No cold storage arm Primary outcome: 30-day survival What we learned: 100 % survival (safe) Minimal reperfusion syndrome

Ravikumar et al, AJT 2016

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OrganOx Metra: Randomized trial

COPE Consortium 220 patients 7 centers (UK, Germany, Spain, Belgium) Randomized to NMLP vs cold storage

Enrollment completed Awaiting the results

Peak AST, graft survival, biliary complications

Preventing EAD and PNF

EAD and PNF Livers from marginal donors are the highest risk for these complications Life-threatening complications Very difficult to treat Require lots of resources …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

• r biliary complications they work very well for a very

long time

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Utilization

UNOS recently reported that only 6,312 of 8,144 of livers that were procured were transplanted Countless more potential donors were never approached Why…? The risk of primary non function

Another way to see discard?

10 20 30 40 50 60 70 80 90 100 Organs from actual DCD donors Donor age criteria met Consent for

• rgan donation

Organs offered for donation Organs retrieved for transplant Organs transplanted Percentage Kidney Liver Pancreas Lungs

1 April 2013 – 31 March 2014

% of all

• rgans

83% 28% 8% 6% Trans

Potential DCD donors (2013-2014)

PNF concerns

Can NMLP reduce PNF?

Severe ischemia reperfusion injury We think PNF is caused by: Glycogen depletion, ATP depletion, anerobic metabolism during storage NMLP reduces ischemia time by 90% NMLP restores glycogen in the liver YES !!! And, NMLP allows you to test for PNF - VIBILITY TESTING

Viability testing

Ex-situ monitoring of liver function Objective, real-time Flow measurements Bile production Biochemical analysis Lactate pH glucose Reduce lactate under 2 mmol/L after 2 hours of NMLP

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First example of viability testing

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 Patient with consented to undergo transplant with a liver turned down by all other UK centers

First example in humans

High risk donor > turned down by all > viability testing > transplant Viability testing

Viability testing

6 livers turned down by all UK centers Donors… DCD with 109 min WIT DCD with BMI of 45 DCD with DRI >3

Viability testing

Transplanted 5 of 6 100% immediate graft function Only 1 required CVVH No biliary complications

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Viability testing

Watson et al, Ann Surg 2016

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

The potential of NMLP

Not to replace cold storage of normal livers

What needs to be studied? PNF

NMLP Viability testing Transplant or discard Randomized Cold vs NMLP Transplanted Outcomes Turned down by all

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Challenges

Somehow allow the data to catch up to the experience described by early adaptors of this new technology Designing a the clinical trial that will show reduced rates of PNF while increasing utilization is very difficult Logitisics at the donor hospital and transportation Cost

Conclusions

Consider the limitations of structuring human clinical trials to demonstrate PNF and organ discard NMLP reduces cold storage from 6-12 hours to 45 min Cold storage is a very injurious time for marginal livers NMLP improves early liver function after transplant and appears to reduce biliary complications 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