Nearly doubled use of donor livers from cadavers compared with ischemic cold storage

Donor liver preservation using a portable, normothermic organ care system (OCS) decreased early allograft dysfunction (EAD) and led to greater organ utilization in liver transplant recipients compared to donor livers preserved by conventional ischemic cold storage (ICS), the first randomized trial of its kind showed.

In a per-protocol analysis of 293 patients, the incidence of EAD was significantly lower at 18% in OCS Liver-preserved livers compared with 31% in the ICS liver-preserved livers (P=0.01), James Markmann, MD, PhD, Massachusetts General Hospital, Boston, and colleagues reported in JAMA Surgery.

OSC Liver-preserved livers also had significantly less evidence of ischemia reperfusion injury as reflected by the degree of moderate to severe lobular inflammation following reperfusion at 6% compared to 13% for ICS-preserved livers (P=0.004), the investigators added.

Importantly, the use of the normothermic machine perfusion system almost doubled the use of donor livers taken from cadavers after cardiac death at 51% compared to 26% for ICS-preserved livers (P=0.007).

“In the early days of liver transplantation, there were attempts to develop active perfusion approaches for organ preservation but the technology was neither portable nor sufficiently advanced to make it widely applicable, and at the same time, ICS was simple and widely available and at least partially effective,” Markmann explained in an email to BreakingMED.

“The OCS Liver does incur a bit more work for the transplant team and is more expensive than ICS but these factors appear to be more than offset by its benefits it that it allows [clinicians] to assess organ function to determine suitability for transplant and improve post transplant function,” he added.

“Together these attributes may make transplants safer and more effective and encourage greater organ utilization,” Markhmann said.

The International Randomized Trial to Evaluate the Effectiveness of the Portable Organ Care System (OCS) Liver for Preserving and Assessing Donor Livers for Transplantation (the PROTECT Trial) is the first U.S. randomized trial for liver perfusion designed to overcome the limitations of ICS.

“The OCS Liver consisted of an integrated system of three components: the OCS Liver console, OCS Liver perfusion set, and OCS bile salt solution for infusion,” the authors explained.

The OCS Liver was readily integrated into all 20 centers that participated in the trial and teams were all trained to perform all OCS Liver instrumentation, management, and assessment of donor livers during the entire preservation period of the trial.

The mean ages of the donors were very similar in both OCS Liver and ICS groups at a mean age of 45.9 years in the OCS Liver donor group and 46.9 years in the ICS donor group. Likewise, the mean age of OCS Liver recipients was 57.2 years versus 58.4 years for ICS liver recipients. Approximately two-thirds of both OCS and ICS recipients were male.

As the authors reported, the use of the OCS Liver significantly reduced the mean cold ischemic time of donor livers to 175.4 minutes compared with 338.8 minutes for ICS donor livers (P<0.001).

They also observed that the risk of graft failure in donor livers who had evidence of EAD was significantly higher than in those livers with no evidence of EAD (P=0.003).

The mean ICU stay was also significantly longer for patients who had evidence of EAD at 7.7 days compared to a mean of 3.4 days for patients who had no evidence of EAD (P=0.04) as was the mean overall hospital stay at a mean of 15.7 days versus a mean of 10.1 days, respectively (P=0.02).

At six months post-transplantation, livers preserved by the OCS Liver preservation system exhibited a significant decrease in ischemic biliary complications at 1.3% compared with 8.5% for livers preserved by conventional ICS, the investigators also noted.

The same was also true 12 months after transplantation at 2.6% versus 9.9%, respectively (P=0.02 for both endpoints).

As Markmann noted, OSC Liver is unlikely to replace ICS, since the highest quality organs may not benefit from normothermic perfusion unless long cold ischemic times are expected.

“But under certain cases in which the quality of the organ is suspect or known to be compromised, normothermic perfusion may enhance outcomes in liver transplant recipients,” Markmann said.

“And perhaps its greatest potential impact is as a means to enable safe transplantation of more than 3,000 donor livers that are discarded each year,” Markmann said.

As the authors pointed out, the inherent uncertainties of livers preserved by ICS make transplant clinicians perhaps more cautious than they need to be when considering organ quality, ultimately leading to underuse of available donor livers for potential transplant recipients.

Commenting on the findings, Ralph Quillin III, MD, and Shimul Shah, MD, both from the University of Cincinnati College of Medicine, Cincinnati, noted that while results are “important and impressive,” a number of questions remain to be answered.

  • Which livers warrant the use of machine perfusion (MP)?
  • Should MP be used only for marginal or donation after circulatory death allografts?
  • Who bears the responsibility of perfusion—organ procurement organizations or transplant centers?

“[J]ust as MP is poised to change the face of liver transplant, it may also shape the future of the transplant workforce,” the editorialists suggested.

As they pointed out, transplantation has long been considered a relatively undesirable field by trainees for a number of reasons, not the least of which are workforce concerns.

“Currently, broader sharing, as well as an increase in DCD donation (donation after circulatory death) has revealed an expanded need for a ’local’ recovery surgeon,” Quillin and Shah noted, adding that: “[And i]ncreased and broad use of MP 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.”

  1. Donor liver preservation using a normothermic organ care system improved patient outcomes following liver transplantation compared with conventional ischemic cold storage.

  2. The use of a normothermic organ care system almost doubled the use of donor livers taken from cadavers after cardiac death compared with livers preserved through conventional ischemic cold storage.

Pam Harrisson, Contributing Writer, BreakingMED™

The study was funded by TransMedics Inc.

Markmann had no conflicts of interest to declare.

Quillin reported receiving personal fees from Natera while Shah reported having received grants from Organ Recovery Systems.

Cat ID: 636

Topic ID: 630,636,636,730,473,192,925