Many Discarded Livers Could Be Safely Transplanted

By Will Boggs MD

June 18, 2020

NEW YORK (Reuters Health) - Viability testing during normothermic machine perfusion (NMP) can identify transplantable livers that would otherwise be discarded, researchers report.

"In these times of organ shortage, far too many organs are turned down for concerns about initial nonfunction based on what are very subjective criteria," said Dr. Darius F. Mirza of the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, in the U.K.

"This trial has shown that with the help of objective criteria derived during normothermic perfusion, we can safely ascertain that these liver grafts will work, and that these initially discarded livers can be used to help in helping overcome the gap between liver need and liver availability," he told Reuters Health by email.

The mortality of patients waitlisted for liver transplantation approaches 32% in the U.S. and 19% in the U.K., prompting moves to use more marginal liver grafts. Currently, this requires matching high-risk livers to lower-risk recipients to achieve acceptable patient survival rates.

NMP reduces preservation-related graft injury (compared with static cold storage), and objective parameters measurable during NMP can be used to assess viability.

Dr. Mirza and colleagues evaluated the potential of NMP to provide objective assessment of the viability of livers currently deemed unsuitable for transplantation and the results of transplantation of those that met predetermined criteria in 22 patients waitlisted for liver transplantation.

During the NMP procedure, 25 of 31 discarded livers quickly recovered metabolic activity and cleared lactate to the target level, but three livers deteriorated within the first four hours, with increasing lactate.

Overall, 22 livers (71%) met the viability criteria and were transplanted following a median total preservation time of 17 hours and 53 minutes, the team reports in Nature Communications.

All 22 patients were alive at day 90 posttransplantation, with 90-day graft survival of 100%. Seven patients (32%) developed early allograft dysfunction and seven patients developed grade 3 or worse complications.

The median duration of stay was 3.5 days in the intensive-care unit and 10 days in the hospital.

At one year, patient survival was 100% and graft survival was 86%. These rates were similar to those of 44 contemporary matched controls (95.5% and 86%, respectively).

The incidence of early allograft dysfunction was higher in the study group (32%) than in the matched controls (9%), as was the incidence of clinically manifest nonanastomotic biliary strictures (18% vs. 2%, respectively).

"This trial demonstrated that NMP provides a way of objectively assessing high-risk organs, and allowed transplantation in a significant proportion of currently unutilized livers without any incidence of primary non-function," the authors conclude. "The use of perfusion technology was associated with increased graft utilization, considerably extended preservation time, and greatly improved transplant logistics."

"Adoption of functional assessment of high-risk livers can increase access to lifesaving transplantation and reduce waiting list mortality," they add.

Dr. Annemarie Weissenbacher of Medical University of Innsbruck, in Austria, and Oxford University Hospitals, in the U.K., recently discussed the future of organ perfusion and reconditioning. She told Reuters Health by email, "This study has to be seen from the perspective that none of these livers would have been transplanted otherwise - they would have been discarded. Therefore, this trial has a 100% success rate as it has to be compared to patients becoming unfit for transplant or dying on the waiting list."

"By applying NMP, viability assessment is possible in DBD (donor after brainstem death) and DCD (donor after circulatory death) livers leading to better organ utilization resulting in successful liver transplantation," she said.

"Long-term results and a higher number of livers assessed by NMP in a similar setting will prove if it would be safe to transplant such livers into higher risk recipients," said Dr. Weissenbacher, who was not involved in the study.

She added, "As suspected, nonanastomotic bile duct strictures in DCD organs are not preventable by using more optimal preservation techniques, as the damage probably caused by warm ischemia cannot be resolved. However, the NMP platform provides the amazing opportunity to study such organs and to think about repair mechanisms, stem-cell administration, pharmacological studies, etc., to counteract/avoid this severe complication."

SOURCE: https://go.nature.com/3hC9SwP Nature Communications, online June 16, 2020.

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