Normothermic Machine Perfusion for Liver Transplant Tied to Improved Outcomes

Normothermic machine perfusion (NMP) to preserve livers prior to transplant was associated with significantly improved clinical outcomes and reduced use of hospital resources compared with static cold storage (SCS), particularly for donations after circulatory death, according to an observational retrospective cohort study.

Those receiving donations after circulatory death preserved with NMP had the lowest early allograft dysfunction rate at 17.5%, compared with 27.3% for donations after brain death preserved with SCS, 36.8% for donations after brain death preserved with NMP, and 50% for donations after circulatory death preserved with SCS (P<0.001), reported Amit K. Mathur, MD, of the Mayo Clinic Arizona in Phoenix, and colleagues in JAMA Surgery.

Patients receiving donations after circulatory death preserved with NMP also had the lowest intraoperative transfusion requirement, needing 700 mL less red blood cell volume than SCS livers and post-brain death livers preserved with NMP. Fresh frozen plasma use was 900 mL lower and cryoprecipitate use was 200 mL lower for NMP donations after circulatory death than the other three types. There were no differences in platelet transfusion.

In addition, post-circulatory death donations preserved with NMP had the shortest length of stay in the hospital, with a median of 5 days versus 6 days for the other groups (P=0.01), and the intensive care unit, with a median of 1.5 days versus 2 to 2.3 days, respectively (P=0.01).

The probability of 1-year cumulative readmission was 86% lower for this group versus the group receiving donations after circulatory death preserved with SCS (P<0.001) and 53% lower for the group receiving donations after brain death preserved with NMP versus donations after brain death preserved with SCS (P<0.001).

“This study has broad implications, highlighting two main advantages of NMP: expanding donor acceptance criteria and enabling safe, extended preservation times,” Mathur and team wrote, noting that before NMP adoption, liver acceptance with donations after circulatory death was restricted to donors ages 65 and younger and located within 500 nautical miles, with limited cold ischemia time (6-7 hours) and donor warm ischemia time of 30 minutes or longer.

Since adopting NMP, our center now accepts liver donations after circulatory death from donors ages 70 and younger, from any distance within the U.S., and with donor warm ischemia time up to 45 minutes, they noted.

“Preservation times now routinely exceed 24 hours, providing logistical flexibility and facilitating use of marginal allografts in complex cases,” they added.

In an accompanying editorial, Satish N. Nadig, MD, PhD, of Northwestern University Feinberg School of Medicine in Chicago, and colleagues noted that “the use of NMP in liver transplant has revolutionized not only how we perform liver transplant but the type of allografts used while maintaining high standards of quality and outcomes.”

“The most notable findings in this article are dramatically improved outcomes in recipients of grafts from donors after cardiac death using NMP,” they wrote. “The benefits of NMP for use with donations after cardiac death grafts, similar to those observed with use of normothermic regional perfusion and hypothermic machine perfusion, should effectively end any consideration of static cold storage after [post-cardiac death] donation.”

For this study, Mathur and colleagues enrolled all 1,086 consecutive adults undergoing liver transplant between January 2019 and December 2023 at the Mayo Clinic Arizona. These included 480 donations after brain death preserved with SCS, 63 donations after brain death preserved with NMP, 264 donations after circulatory death preserved with SCS, and 279 donations after circulatory death preserved with NMP.

Median age of recipients was 60, and 36.7% were women. There were no significant differences between NMP and SCS groups in donor age, body mass index (BMI), distance to recipient hospital, or organ share type for donations after brain death. For donations after circulatory death, however, NMP donors were older, had a higher BMI, were farther from the recipient hospital, and were sourced from more national share types compared with SCS donors.

Compared with those receiving post-brain death donations, recipients of post-circulatory death livers were older, had a lower allocation Model of End-State Liver Disease (MELD) score, and were more likely to need the liver for hepatocellular carcinoma. Meanwhile, recipients of NMP livers had lower allocation MELD scores than those receiving SCS livers for both donations after post-brain and post-circulatory death.

For secondary outcomes, acute kidney injury occurred less often in patients receiving livers preserved with NMP (31.1%) versus SCS (47.4%, P=0.001) among donations after circulatory death.

Livers preserved with NMP had an overall 78% lower graft failure than those preserved with SCS for both donation types (HR 0.22, 95% CI 0.10-0.49, P<0.001). The risk reduction in graft failure was even lower (87%) among donations after circulatory death (HR 0.13, 95% CI 0.05-0.33, P<0.001).

Patients receiving NMP livers had 30-day and 1-year survival rates of 100% and 98.5%, compared with 98.5% and 95.4%, respectively, for SCS donations. Risk of death was 69% lower overall with NMP preservation than with SCS preservation (HR 0.31, 95% CI 0.12-0.80, P=0.02).

The authors said that cost-benefit analysis studies will need to assess costs of NMP versus SCS, but they anticipate NMP yielding cost benefits.

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