Normothermic Machine Perfusion Shows Promise in High-Acuity Liver Transplants

A recent study found normothermic machine perfusion in liver transplants significantly reduced early liver complications compared with static cold storage and showed promising outcomes in complex patient cases.¹

The wait time for receiving a liver can range from 30 days to 5 years, depending on how badly someone needs a new liver and other factors, such as age, location, blood type, body size, overall health, and the availability of a matching liver.² The organ preservation can also impact when a patient receives their liver.

Before VA investigators developed the warm perfusion technique in 2020, a method used to keep donor organs alive with an artificial circulatory system, the organ was placed in cold storage which only preserved the tissue for 6 to 30 hours.³ With prefusion, donor hearts are preserved twice as long, extending from 6 hours in cold storage to 12 hours.

Normothermic machine perfusion brings many advantages—extending preservation time, reducing ischemic injury, and increasing the number of usable donors.¹ However, patients with high-acuity illnesses require donors that fit more specific criteria, which limits organ availability and increases wait time.

Investigators sought to compare the outcomes of adult liver transplants that used normothermic machine perfusion with those that used standard static cold storage. They used propensity score matching, yielding 28 paired cases of normothermic machine perfusion and static cold storage.

This single-center retrospective analysis included 176 transplants performed between November 1, 2022, and November 30, 2023. Most of the sample was male (71%), and the mean age was 51 years.

“Prior studies excluding most HILT indications reported initial benefits of [normothermic machine perfusion] vs [static cold storage], but the present study, to our knowledge, was the first and largest to analyze practical applications of [normothermic machine perfusion] for complex [high-acuity liver transplant] cases,” wrote investigators, led by Samer S. Ebaid, MD, PhD, MS, from the David Geffen School of Medicine at UCLA.

A high-acuity liver transplant was defined as a Model for End-Stage Liver Disease 3.0 score > 30. These patients were given vasopressors in the ICU before transplant, and underwent a multiorgan transplant, a combined liver and cardiac surgery, or a retransplant.

Outcome measures included total preservation time, lactate clearance and bile production on NMP, and lactate and base excess at the end of liver transplant. Another outcome included early allograft dysfunction, defined as aspartate aminotransferase [AST] >2000 IU/L, bilirubin ≥10 mg/dL, or international normalized ratio ≥1.6 up to 7 days postoperatively. Additional outcomes included post-liver transplant length of stay, 6-month unplanned reoperation and ischemic cholangiopathy rates, and 90-day and 6-month mortality.

More organs from donors who passed away from cardiac deaths were preserved with normothermic machine perfusion than static cold storage (32% vs 4%; P < .01). Compared with cold storage, the organs in normothermic machine perfusion had significantly longer total preservation time (716 vs 392 minutes; P < .001), with great lactate clearance (median 4.63 to 0.75 mmol/L; P < .001) and bile production (median 50 mL).

Furthermore, the normothermic machine perfusion group had significantly lower median lactate (2.7 vs 4.7 mmol/L; P = .04), greater base excess (-2 vs -4; P = .03), lower median peak AST (333 vs 470 IU/L; P = .003) and alanine aminotransferase (314 vs 507 IU/L; P = .002), and lower early allograft dysfunction incidence (7% vs 29%; P = .04).

Investigators observed no differences between normothermic machine perfusion and static cold storage for unplanned reoperation, ischemic cholangiopathy, or post-liver transplant LOS.

Among 28 normothermic machine perfusion cases, 61% had high-acuity liver transplant indications, 53% had a Model for End-Stage Liver Disease 3.0 score > 30, and 41% had pre-liver transplant vasopressors in the ICU. The team saw high-acuity liver transplant outcomes using normothermic machine perfusion were favorable, noting low rates of postreperfusion syndrome (6%), early allograft dysfunction (6%), unplanned operation (12%), and 90-day and 6-month mortality (6%, with 1 death due to cardiac tamponade).

“Although limited by small sample size and retrospective design, this study found that dynamic perfusion time gained by [normothermic machine perfusion] allowed for [liver transplant] with excellent outcomes using livers from extended criteria donors and complex care of patients with high-acuity illness and hemodynamic instability or who need multiorgan transplant, combined [liver transplant with cardiac surgery, or retransplant,” investigators wrote.

References

1. ^{Ebaid SS, Kimelman FA, Maeda K, et al. Liver Transplant Using Normothermic Machine Perfusion in Patients With High-Acuity Illness. JAMA Surg. Published online October 30, 2024. doi:10.1001/jamasurg.2024.4101}
2. ^{The Liver Transplant Process. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/liver-disease/liver-transplant/preparing-transplant#:~:text=The%20waiting%20period%20for%20a,to%20more%20than%205%20years.&text=How%20long%20you%20will%20wait,you%20need%20a%20new%20liver. Accessed November 4, 2024.}
3. ^{Keeping Donor Organs Viable for Transplant. US Department of Veterans Affairs. January 24, 2020. https://www.research.va.gov/research_in_action/Keeping-donor-organs-viable-for-transplant.cfm#:~:text=After%20an%20organ%20is%20surgically,on%20the%20type%20of%20organ. Accessed November 4, 2024.}