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Patients who received liver transplants with TransMedics' Organ Care System (OCS) liver perfusion device were less likely to experience early allograft dysfunction and ischemic biliary complications, the randomized OCS Liver PROTECT trial found.

In an intent-to-treat analysis involving 300 patients undergoing liver transplantation, 18% of recipients assigned to transplant with the OCS system had early allograft dysfunction compared to 31% of those receiving ischemic cold storage (ICS)-preserved livers (P=0.01), reported James Markmann, MD, PhD, of Massachusetts General Hospital in Boston, and colleagues.

After transplantation, recipients in the OCS group had a significantly lower incidence of ischemic biliary complications versus the ICS group at 6 months (1.3% vs 8.5%, respectively) and 1 year (2.6% vs 9.9%; P=0.02 for both), the authors wrote in , and had significantly less ischemia-reperfusion injury, as indicated by a reduction in moderate-to-severe lobular inflammation (6% vs 13%; P=0.004).

"The PROTECT trial showed superior short-term and mid-term clinical outcomes and higher number of donor livers used for transplant," the group concluded. "The advent of portable, extracorporeal, donor liver machine perfusion offers for the first time a convenient and effective approach to both assess and enhance donor liver function, thereby improving transplant safety, expanding the liver donor pool, and reducing waiting list mortality."

No between-group difference was seen in the percentage of donation after brainstem death (DBD) livers used for transplant, but twice as many donation after circulatory death (DCD) livers were able to be used in the OCS liver group (51% vs 26% with ICS; P=0.007).

Findings from the trial led to of TransMedics' OCS Liver System in September 2021 for use with DBD or DCD organs. The approval followed a near-universal endorsement from the agency's Gastroenterology and Urology Devices Panel last July.

"The liver transplant community is still in need of guidance in how to best use this technology," noted Ralph Quillin III, MD, and Shimul Shah, MD, both of the University of Cincinnati in Ohio, in an .

"Increased and broad use of machine perfusion will require a further expansion of the transplant workforce and could pave the way for a career path in transplantation as an organ recovery and preservation specialist," Quillin and Shah said.

However, the duo cautioned that "machine perfusion will add to the already increasing cost and complexity of liver transplant seen following the implementation of acuity circles and broader sharing."

From November 2016 to October 2019, the PROTECT trial randomized 300 patients listed on the national waitlist 1:1 to a liver transplant using the OCS system (n=153 participants) or standard ICS (n=147 participants) protocol at 20 donor hospital sites.

The primary efficacy endpoint was early allograft dysfunction, while severe graft-related adverse events within 30 days of transplant was the primary safety endpoint. Secondary outcomes included ischemic biliary complications, assessment capability of donor organs with the OCS device, extent of reperfusion syndrome, and survival (30-day survival after transplant was identical for the two groups, at 99.3%).

Two-thirds of participants in the study were men and the mean age was 57-59 years. About half had alcoholic cirrhosis, 26-35% had chronic hepatitis, and 18-24% had nonalcoholic steatohepatitis. Donors were a mean age of 46-47 and 58-62% had multiple comorbidities.

Donor organs had to have at least one of the following: minimum age of 40 years for donor, at least 6 hours of expected cross-clamp/cold ischemic time, maximum age of 55 for DCD donors, and macrosteatosis in no more than 40% of the liver.

OCS donor livers were perfused for 277 minutes, on average. Despite longer total cross-clamp time, use of the OCS device significantly reduced the average cold ischemia time of donor livers.

The trial had several limitations, the researchers acknowledged, including the lack of blinding and the practice of re-randomization if a donor liver had to be rejected.

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