June 18th 2020

VITTAL Trial demonstrates viability testing with OrganOx metra could recover 7 in 10 discarded donor livers

In a landmark clinical trial, published in Nature Communications this week, 7 in 10 donor livers which were previously rejected for transplant were assessed and transplanted following perfusion on the OrganOx metra.

The VITTAL trial (Transplantation of discarded livers following viability testing with normothermic machine perfusion) involved the perfusion of 31 livers which were previously determined to be unsuitable for transplantation by all liver transplant centres in the UK. Livers were perfused on the OrganOx metra and assessed against pre-determined viability criteria. 22 of the 31 livers (71%) met criteria and were transplanted. Early outcomes were excellent with 100% 90-day graft and patient survival (primary endpoint of the study). One-year patient survival was also 100%.

The trial could have important implications for thousands of patients waiting for a liver transplant. Currently approximately a third of donated livers are rejected because they are not considered to be of good enough quality for transplantation. The use of the metra could greatly increase the utilisation of donated organs and reduce waiting list mortality.

Mr Hynek Mergental, Honorary Senior Lecturer at the University of Birmingham and Consultant Surgeon at the UHB Liver Unit said: “Whilst liver transplantation is one of the most advanced surgical procedures, up to now, there has been no objective means to assess suitability of donor livers for transplantation. The VITTAL trial validated our pre-clinical research and pilot clinical observations and these viability criteria can now guide transplant teams worldwide to provide access to the life-saving transplantation to more patients in need. “

VITTAL project lead, Professor Darius Mirza, Consultant Transplant Surgeon at University Hospitals Birmingham NHS Foundation Trust and Honorary Professor at the University of Birmingham, said: "During normothermic machine perfusion the liver begins to function and behave in a similar way to how it would if it was transplanted, which allows surgeons to assess whether a liver will function following transplantation before it is transplanted into a patient. This challenging study was designed to assess function of discarded livers in the real-life situation. The major challenge in this pioneering clinical trial was to assure patients safety while pushing the envelope of sub-optimal liver utilisation.”

Mr Thamara Perera, Consultant Transplant Surgeon at UHB explains: “This groundbreaking trial has proven that objective parameters can be used for making a decision to use a borderline liver. The observed 100% study participants post-transplant survival was reassuring and provided our patients and the surgical team with confidence to implement and further expand this approach, which now helps the sickest patients on our waiting list to underwent transplantation sooner and safer.”

Dr Simon Afford, Reader in Liver Immunobiology at the of the University of Birmingham’s Institute of Immunology and Immunotherapy, said: “It has long been recognised that as a consequence of our population aging the quality of donated livers keeps declining. Based on our latest discoveries we believe that in the near future the machine perfusion platform will facilitate therapeutic interventions to improve liver viability. We expect we will be able salvage even more organs than 70% observed in the VITTAL trial, including livers from donors with known alcohol misuse or obesity.”

Tim Knott, Head of Innovation Programmes at the Wellcome Trust, the funders of the clinical trial, said: “Many more patients who need liver transplants will benefit from this technology. Giving surgeons the tools to assess if a liver transplant will be viable will help the thousands of people who have chronic liver disease globally.”

John Forsythe, Medical Director of Organ Donation and Transplantation for NHS Blood and Transplant, said: “New techniques of Organ perfusion and preservation are a vital developing area of organ donation and transplantation. We are delighted that a number of doctors and scientists in the UK are leading the way in this field of research. Each year a small number of donated organs are not transplanted for a variety of reasons. Transplant success relies on a significant amount of activity taking place in a short space of time. New techniques are already allowing us to transplant donated organs that would not have been possible in the past. More research in this area is likely to increase that ability.”

The trial was published in Nature Communications: https://www.nature.com/articles/s41467-020-16251-3