Prolonged Perfusion Preserves Donor Livers, Allows Flexible Transplantation Timeline

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Liver transplantation after prolonged preservation with dual hypothermic oxygenated machine perfusion yielded similar outcomes to standard perfusion, showing no compromised donor liver quality and equal safety for recipients.

Vincent de Meijer, MD, PhD | Credit: University Medical Center Groningen

Vincent de Meijer, MD, PhD

Credit: University Medical Center Groningen

The landscape of liver transplantation may be on its way to a complete transformation thanks to findings from a first-in-human clinical trial demonstrating the safety and feasibility of prolonged liver preservation with dual hypothermic oxygenated machine perfusion, suggesting the days of immediate, around-the-clock liver transplants may be nearing an end.

Among 24 patients who received a liver transplant, prolonged dual hypothermic oxygenated machine perfusion (≥ 4 hours) for brain-dead donor livers did not compromise donor liver quality and was equally safe compared to standard perfusion (1-2 hours) – although further research is needed to confirm and expand upon the results, these findings show promise for improving logistical efficiency and allowing for the optimal utilization of deceased donor livers while maintaining favorable outcomes.1

Advances in medical technology now allow donor organs to remain viable for transplant hours after being removed from the body, although the specific timeline varies based on the organ being transplanted. Still, this period is limited and often requires immediate action on behalf of surgeons and the donor recipient, but new data about the safety and feasibility of prolonged liver preservation with dual hypothermic oxygenated machine perfusion may allow for more flexibility in this formerly rigid transplantation schedule.1,2

“Liver transplantations no longer have to be performed immediately after a donor organ becomes available. Performing such complex and high-risk surgeries in the middle of the night is no longer necessary as a result,” Vincent de Meijer, MD, PhD, professor of surgery and head of the liver transplant program at the University Medical Center Groningen, explained in a press release.3

To compare the safety and feasibility of prolonged versus conventional dual hypothermic oxygenated machine perfusion for brain-dead donor livers, de Meijer and a team of investigators assigned patients ≥ 18 years of age undergoing liver-only transplantation to livers exposed to both perfusions based on donor hepatectomy end times. Coined the Prolonged Dual Hypothermic Oxygenated Machine Perfusion (DHOPE-PRO) trial, the prospective, dual-arm clinical trial was conducted at the University Medical Center Groningen.1

Patients were excluded from the study if they were on a high-urgency status, had a laboratory Model for End-stage Liver Disease (MELD) score >30, or underwent combined organ transplantation. Patients receiving a graft from a donation after circulatory death donor, a donor with a body weight <40 kg, with an untreated human immunodeficiency virus, or untreated hepatitis B or C virus infection, or with estimated graft steatosis >30% were also excluded.1

During transportation to the recipient transplant center, livers were preserved by traditional static cold storage, regardless of whether they were in the intervention or control group. Investigators noted the trial did not interfere with the regular process of organ allocation or acceptance and for logistical reasons, they were unable to blind the recipient and transplant team.1

The primary safety endpoint was the incidence of serious adverse events and serious adverse device events up to 30 days after liver transplantation. Serious adverse device events included device error leading to termination of the perfusion and deviation from the perfusion protocol, while serious adverse events included increased hepatic resistance, post-reperfusion syndrome, primary non-function, early allograft dysfunction, vascular complications, and massive biliary necrosis.1

Investigators additionally defined the primary feasibility endpoint as the number of patients assigned and successfully receiving a prolonged dual hypothermic oxygenated machine perfusion-perfused liver graft.1

Between November 1, 2020, and July 16, 2022, investigators assessed 120 consecutive adult patients for eligibility, of whom 89 were transplanted during the study period. Of those patients, 24 were included in the study. Investigators noted the baseline characteristics of the donors, recipients, and static cold preservation time during transport to the recipient hospital were similar across both trial groups.1

The median recipient transplant surgery duration in the prolonged group (7.5 hours; interquartile range [IQR], 6.9 to 8.7) was almost 2 hours shorter than that of the control group (9.3 hours; IQR, 8.0 to 11.3; P = .02). Inherent to the intervention, the median machine perfusion time was longer for the prolonged group (9.3 hours; IQR, 8.0 to 10.1) compared to the control group (2.2 hours; IQR, 2.0 to 2.4), and the median total preservation time was longer for the prolonged group (14.5 hours; IQR, 14.0 to 15.6) than the control group (7.9 hours; IQR, 7.6 to 8.6).1

Investigators pointed out severe adverse events and serious adverse device events were evenly distributed, affecting 3 patients in each group (25%; 95% Confidence interval [CI], 3.9 to 46%; P = 1). Post-reperfusion syndrome occurred in 3 patients (25%; 95% CI, 3.9 to 46%) in the prolonged group and 2 patients (17%; 95% CI, –2.3 to 36%) in the control group. A single device error occurred in the control group where the pressure sensor malfunctioned during machine perfusion, leading to inaccurate pressure measurements and unreliable flows.1

All patients assigned to either the intervention group or control group successfully received a liver graft perfused with either prolonged or control dual hypothermic oxygenated machine perfusion. Investigators also pointed out markers of ischemia-reperfusion injury and oxidative stress were similar between the groups.1

“This pioneering clinical trial demonstrates the safety and feasibility of [dual hypothermic oxygenated machine perfusion] in prolonging the preservation time of donor livers to enable daytime transplantation. The ability to extend the preservation window to up to 20 h using hypothermic oxygenated machine preservation at a 10 °C temperature has the potential to reshape the landscape of liver transplantation,” investigators concluded.1

References:

  1. Brüggenwirth IMA, Lantinga VA, Lascaris B, et al. Prolonged hypothermic machine perfusion enables daytime liver transplantation – an IDEAL stage 2 prospective clinical trial. EClinicalMedicine. 10.1016/j.eclinm.2023.102411
  2. Donor Alliance. What is the Time Frame for Transplanting Organs? April 23, 2023. Accessed January 11, 2024. https://www.donoralliance.org/newsroom/donation-essentials/what-is-the-time-frame-for-transplanting-organs/
  3. University Medical Center Groningen. Liver transplantation becomes a 9-to-5 operation due to perfusion machine. EurekAlert! January 9, 2024. Accessed January 11, 2024. https://www.eurekalert.org/news-releases/1030664
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