Many of you may have attended all or some of the trifecta of Spring 2024 national and global congresses for the transplantation community: the European Liver and Intestine Transplant Association (ELITA) Summit 2024, organized by European Society for Organ Transplantation (ESOT) in April; the 2024 Annual Congress of the International Liver Transplantation Society (ILTS) in May; and in June the American Transplant Congress (ATC), the Joint Annual Meeting of the American Society of Transplant Surgeons (ASTS) and the American Society of Transplantation (AST). Each congress/meeting contributed significantly to the dissemination of research and literature that advance innovation for transplant professionals and recipients.

For Bridge to Life, these events provided a major opportunity to present the latest data on Hypothermic Oxygenated Perfusion (HOPE), in conjunction with our VitaSmart Machine Perfusion technology.

Here’s our news from ATC 2024:

We announced the latest findings from the Bridge to HOPE clinical trial, utilizing the VitaSmart Machine Perfusion System. The trial evaluates the safety and efficacy of static cold storage (SCS), the current standard for ex-vivo organ preservation, compared to SCS followed by Hypothermic Oxygenated PErfusion (HOPE) prior to transplantation of extended criteria donation after brain death (DBD) and donation after circulatory death (DCD) livers. The one-year patient follow-up results, involving 219 participants, produced the following key results:

• A significant reduction in early allograft dysfunction (EAD) in the HOPE group (20%) compared to the SCS group (37%), the primary endpoint of the trial with a statistically superior finding (p=.003).
• A significantly shorter median hospital stay for the HOPE group (8 days) compared to the SCS group (11 days, p=.04).
• Favorable trends for HOPE, including fewer serious adverse events, lower rates of Clavien-Dindo grade >3 events (HOPE = 51%, SCS = 60%), reduced incidence of clinically significant DCD ischemic cholangiopathy (HOPE = 11%, SCS = 19%), and lower rates of DCD graft failure (HOPE = 7%, SCS = 19%) and re-transplantations.
• No device-related adverse events were reported.

David J. Reich, MD, Surgical Director of the Liver Transplant Program and Chief of Innovative Technology and Therapeutics at the Cleveland Clinic Transplant Center in Weston, FL presented the results as Lead Investigator for the trial.

These results, along with data from other HOPE studies conducted in Europe, collectively validate the safety and effectiveness of this therapy.

Furthermore, the ease of use and significant cost difference between Normothermic Machine Perfusion (NMP) and HOPE systems, position this device to be highly disruptive in the current US market, where the only option for perfusing organs today is an extremely expensive and highly complex normothermic system, which creates a disruption of the current workflow. Despite objective clinical evidence showing that machine perfusion is superior to static cold storage – regardless of whether perfusing with a normothermic or hypothermic system – many transplant centers still struggle with deciding when to use perfusion due to its high cost, often reserving it for higher-risk organs. At Bridge to Life, our goal is to make this therapy affordable and accessible for ALL liver transplants. That’s why we call our research program HOPE for ALL.

Other ATC 2024 presentations included:

Decreased Ischemic Cholangiopathy With Hypothermic Oxygenated Perfusion: Sub Analysis Of Biliary Outcomes From The Us Pivotal Multicenter Trial Of The VitaSmart For Hope In Liver Transplantation, D. Reich, Cleveland Clinic, Weston, FL et al.

Early Allograft Dysfunction As A Clinical Trial Primary Outcome Measure Correlates With Later Outcomes: Analysis From A US Pivotal Multicenter Medical Device Trial Of Hypothermic Oxygenated Perfusion For Liver Transplant, D. Reich, Cleveland Clinic, Weston, FL et al.

Economic Assessment Of Hypothermic Oxygenated Machine Perfusion In Liver Transplantation: Interim Analysis, D. Axelrod, University of Iowa, Iowa City, IA et al.

Our news from ILTS 2024 included:

Samuel James Tingle, MD, et al, Newcastle University, Translational and Clinical Research Institute, Newcastle, United Kingdom, presented his meta-analysis of seven clinical trials – Machine perfusion in liver transplantation: Cochrane review and meta-analysis – and confirmed significant improvement in several parameters with HOPE compared to static cold storage and normothermic machine perfusion (NMP). While both technologies proved to be superior to SCS, there is no good evidence that NMP has the same benefits over SCS in terms of these clinically relevant outcomes.

Other ILTS 2024 abstracts included:

Hypothermic oxygenated perfusion (HOPE): Results of our experience in the first 31 liver transplants, Dora Gomez Pasantes, MD et al, University Hospital of A Coruña, A Coruña, Spain

Impact of hypothermic organ perfusion in small grafts in living donor liver transplantation to avoid small-for-size syndrome: safety & feasibility pilot study- phase-I HOPE-L trial, M. Pardasani, MD, M. Rela, MD et al, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India

Single center evolution of DCD donor utilization for liver transplantation: from perceived marginality to routine and beyond, Matteo Ravaioli, MD, PhD, et al, University of Bologna, Bologna, Italy

Machine perfusion, an ace up your sleeve: unlocking liver graft potential from donation after circulatory death and previously rejected extended criteria donors, Matteo Ravaioli, MD, PhD, et al, University of Bologna, Bologna, Italy

As you can see, we have been quite thorough and comprehensive in our research and confirmation of early results of the use of HOPE for liver transplantation. We remain optimistic about results-to-date, and are on track to complete the trial later this year. We then plan to submit a PMA to the U.S. Food and Drug Administration by early 2025.

While we have a full schedule of regional and local presentations during the summer months, we are looking forward to the 30th International Congress of The Transplantation Society (TTS 2024) to be held in Istanbul, Turkey, September 22-25, 2024. We hope to see you there!

Research Innovations in Organ Preservation:

The Role Mitochondria Mechanisms

Groundbreaking research is underway by a team at the Cleveland Clinic Transplant Center, led by Andrea Schlegel, MD, MBA. She is an academic transplant surgeon who specializes in liver transplantation and hepatobiliary surgery. Dr. Schlegel and colleagues are investigating the critical role of mitochondria mechanisms in evaluating long-term graft viability, which will support more successful organ transplants. This new focus on mitochondria’s critical role in organ viability - and the significance of flavin mononucleotide (FMN) as a potential biomarker - provides the opportunity to increase organ utilization whilst minimizing post-transplant complications and rejection, saving more lives and improving quality of life to thousands of patients.

“With an increasing number of candidates on the waiting lists and a worldwide lack of suitable donors, there is an urgent need to better understand the biological mechanisms as they relate to transplantation,” Dr. Schlegel says. “Our mitochondrial studies focus on the critical element of underlying inflammation that can lead to organ dysfunction and recipient complications after transplantation.”

Prof. Schlegel’s laboratory aims to identify organs that can immediately function after transplant through their viability assessment, avoiding complications and graft loss or recipient death.

“Identifying the mechanisms of mitochondrial dysfunction that lead to ischemia- reperfusion injury and ongoing inflammation after organ transplantation is key,” says Dr. Schlegel.

“Our research has the potential to determine long-term graft survival. As researchers, our large clinical transplant program at the Cleveland Clinic Transplant Center, gives us a unique opportunity to explore novel mechanisms in the laboratory with direct transfer to clinical practice of organ perfusion and transplantation, and save lives.”

– Dr. Andrea Schlegel

Transplantation in the News: The Good and the Misleading

This past April, National Donate Life Month came into focus, illuminating the urgent importance of organ, eye, and tissue donation. This dedicated month honored the incredible donors and their families whose selflessness transforms lives through organ transplants. An outcome of this awareness is the increased media attention on transplantation news. A good deal of organ transplantation news has focused on xenotransplantation, which has long been a dream of surgeons because of the chronic underutilization of available human organs. That is projected to change, as organ preservation techniques become more sophisticated and the availability of transplantable human organs increases.

A notable article in April in The New York Times was unusual in showcasing developments in human organ preservation. While it’s heartening to see mainstream media shed light on transplantation, there’s an equally important aspect of the story that warrants consideration alongside this commendable effort.

According to The New York Times, there’s a significant transformation underway in the field, primarily fueled by technologies enabling clinicians to temporarily preserve organs outside the body.

Known as perfusion, this technique is revolutionizing every aspect of organ transplantation, from surgical procedures to donor eligibility criteria and recipient outcomes. Notably, transplant programs embracing perfusion are witnessing an increase in the number of organs transplanted. While this report highlights significant progress, it predominantly focuses on normothermic machine perfusion, potentially giving the impression that this alone represents the latest advancement in the field.

Normothermic machine perfusion is a method employed to maintain organs outside the body at normal body temperature (37°C). Despite certain benefits it offers over the conventional static cold storage method, it comes with a substantial price tag and demands significant resource allocation for upkeep. Consequently, many contend that its cost presents a major barrier to sustainable adoption.

However, the article’s assertion that blood is indispensable for maintaining organ viability doesn’t hold true when Hypothermic Oxygenated PErfusion (HOPE) is employed. Through HOPE, organs are cooled to temperatures typically ranging between 4°C and 12°C, significantly reducing their metabolic rate to about 10% of normal. Moreover, the system delivers oxygenated perfusion to the dormant organ while it awaits transplantation. Crucially, this oxygen-rich perfusion revitalizes the mitochondria, the powerhouse and energy reservoir of the cells. Essentially, this process primes the cells before transplantation, optimizing clinical outcomes and potentially mitigating the dreaded reperfusion injury that many transplant patients experience shortly after the life-saving surgery.

Although currently only available outside of the US, Hypothermic Oxygenated PErfusion (HOPE) clinical data is accumulating and, at least in these initial stages, providing comparable or even superior outcomes compared to normothermic systems. While observing a hypothermic machine perfuse an organ may not hold the same visual appeal as witnessing a normothermic system in action, the true elegance of a HOPE system lies in its simple design. This simplicity translates into widespread acclaim for its ease of use, minimal monitoring needs, and more cost-effective pricing.

While normothermic blood-based systems have their place, they do come with inherent tradeoffs. While they may attract attention of lay press, hypothermic systems provide a more sustainable and efficient option without disrupting existing clinical workflows. Exploring alternative methods for recharging mitochondria and mitigating reperfusion injury is crucial for the progression of organ perfusion technologies.

See the article above on Dr. Andrea Schlegel’s research on the role of mitochondria in organ preservation elsewhere in this Newsletter.

Bridge to Life on Social Media

• The 1st National UK HOPE Masterclass, organized by Bridge to Life in collaboration with the Herrick Society, offered a fantastic platform for engaging discussions among colleagues in the transplant community. One delegate remarked, “I have learned a lot and enjoyed the discussion.” We look forward to developing this program in the future.
•  Bridge to Life also co-organized the III Jornada HOPE Iberia, which was kindly hosted by Hospital Universitario Gregorio Marañón, Madrid. Maria Sanchez from Bridge to Life commented: “Many thanks to Yuri Boteon, MD, PhD, BCMAS, FACS for sharing through a very interesting presentation, the excellent work done by him and his team using HOPE in Brazil, that showed that boundaries can be pushed to improve patients’ lives. Bridge to Life, and in particular, the team in Iberia, really appreciate your time, effort and dedication and we look forward to further future collaboration. Obrigado!” Dr. Boteon responded:“Pleased to share our Brazilian experience with HOPE on the III Jornada HOPE Iberia today. We were once told, “You can beat the world by doing good things for patients”. This must be the main purpose, and all the rest is the consequence. Thank you, Amanda Pinter Carvalheiro da Silva Boteon and all our team for the effort to deliver the very best to our patients.”

• Bridge to Life was thrilled to support the inaugural event of the New England Donor Services golf outing on a picture-perfect New England summer day. It’s always a pleasure to come together for such a meaningful cause.
• Bridge to Life was proud to partner with Hospital Santo António, Porto for their transplant seminar IX Seminario de Enfermagem em Transplantacao. Maria Sanchez Mendi, our International Manager of Medical Affairs, hosted a session on the implementation of HOPE highlighting the benefits of this simple perfusion protocol.
• Philipp Dutkowski led the ILTS 2024 Knowledge Hub discussion on the treatment and assessment of liver grafts during hypothermic oxygenated perfusion (HOPE).

Upcoming Company Holidays:
Monday, September 2, 2024 – Labor Day