Normothermic Machine Perfusion Improves Liver Transplant Outcomes, Lowers Resource Use

Normothermic machine perfusion (NMP) in liver transplantation (LT) is associated with better graft and patient survival, reduced early allograft dysfunction, and lower hospital resource use, according to findings from a recent study.1

The single-center cohort study, coined by investigators as one of the largest to date on NMP’s impact on LT outcomes, was conducted at the Mayo Clinic in Arizona and highlights several benefits of NMP over static cold storage (SCS), especially in donation after circulatory death (DCD) allografts, including lower transfusion requirements, operative time, length of stay (LOS), readmissions, acute kidney injury (AKI) incidence, and 1-year graft and patient survival.1

“To our knowledge, this analysis represents the largest single-center series on early hospital resource use and LT outcomes following NMP implementation,” Amit Mathur, MD, a transplant, hepatobiliary, and pancreas surgeon and surgical director for the liver transplant program at Mayo Clinic in Arizona, and colleagues wrote.1

According to data from the Organ Procurement and Transplantation Network, more than 100,000 men, women, and children are on the US national transplant waitlist, with another person added every 8 minutes. As of September 2024, nearly 10,000 people on the waitlist were seeking a liver transplant. To address the high demand for LT, maximizing the use of deceased donor livers is essential but often hindered by ischemic injury during recovery, SCS, and reperfusion associated with current liver allograft preservation processes.1,2

To compare LT outcomes between donation after brain death (DBD) and DCD allografts preserved with NMP or SCS, investigators conducted a single-center, retrospective observational cohort study including 1086 consecutive adult LTs performed between January 2019 and December 2023 at the Mayo Clinic in Arizona. Outcomes of DBD-SCS (n = 480); DBD-NMP (n = 63); DCD-SCS (n = 264); and DCD-NMP (n = 279) transplants were compared.1

The primary outcomes were early allograft dysfunction (EAD), intraoperative transfusion, and post-LT hospital resource use, including LOS and readmissions. Secondary outcomes included AKI and 1-year graft and patient survival.1

Among the cohort, the median age was 60.0 years (interquartile range [IQR], 52.0-66.0) and 36.7% of participants were female.1

Investigators noted the EAD rate was lowest in the DCD-NMP group (17.5%) compared with DCD-SCS (50.0%), DBD-NMP (36.8%), and DBD-SCS (27.3%) (P = .001). DCD-NMP patients also had significantly reduced volumes of intraoperative blood component transfusions compared with the other groups. Specifically, the DCD-NMP group required 700 mL less red blood cell volume (median volume, 2100 mL; IQR, 1400- 3500) compared to median volumes for DCD-SCS (2800 mL; IQR, 1400-4550); DBD-NMP (2800 mL; IQR, 1578-4700); and DBD-SCS (2800 mL; IQR, 1670-4480) (P = .03).1

Further analysis revealed hospital and intensive care unit LOS were shortest in DCD-NMP, with median LOS of 5 days (IQR, 4.0-7.0; P = .01) and 1.5 days (IQR, 1.2-3.1; P = .01), respectively.1

Results showed the estimated cumulative probability of any readmission within 1-year posttransplant was 86% lower for DCD-NMP than DCD-SCS (HR, 0.14; 95% CI, 0.09-0.22; P <.001) and 53% lower for DBD-NMP than DBD-SCS (HR, 0.47; 95% CI, 0.26-0.87; P <.001). AKI events were significantly lower in the DCD-NMP group (31.1%) than in the DCD-SCS group (47.4%) (P = .001).1

Additionally, compared with SCS, the NMP group had a 78% overall reduction in 1-year graft failure (hazard ratio [HR], 0.22; 95% CI, 0.10-0.49; P < .001). For DCD allografts, investigators pointed out the risk reduction was even more pronounced, with an 87% decrease in graft failure (HR, 0.13; 95% CI, 0.05-0.33; P <.001).1

Investigators also observed a 69% relative risk reduction for patient mortality with NMP compared to SCS (hazard ratio [HR], 0.31; 95% CI, 0.12-0.80; P = .02). However, they noted subgroup analysis did not demonstrate differences for DCD LT (HR, 0.19; 95% CI, 0.06-2.0; P = .23) or DBD LT (HR, 0.79; 95% CI, 0.19-3.45; P = .78).1

Investigators outlined multiple limitations to these findings, including limited causal inference due to NMP not being randomized and having varying criteria over time; the potential for era effects and selection bias; and the short LOS observed in the study.1

“The benefits of NMP for use with DCD 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 DCD donation,” Satish Nadig, MD, PhD, the Edward G. Elcock Professor of Surgery at the Northwestern University-Feinberg School of Medicine, and colleagues wrote in an invited commentary.3

References

1. Nguyen MC, Zhang C, Chang YH, et al. Improved Outcomes and Resource Use With Normothermic Machine Perfusion in Liver Transplantation. JAMA Surg. doi:10.1001/jamasurg.2024.6520
2. Health Resources and Services Administration. Organ Donation Statistics. October 2024. Accessed January 29, 2025. https://www.organdonor.gov/learn/organ-donation-statistics
3. Borja-Cacho D, Dietch Z, Nadig SN. Machine Perfusion and Liver Transplantation—The Future Is Now. JAMA Surg. doi:10.1001/jamasurg.2024.6529