The rise of the machines…
Liver transplantation is a highly successful treatment of end-stage liver disease, acute liver failure and early-stage primary liver cancer. Approximately 11,000 people a year succumb to Liver Disease in England, and the average age of death from liver disease, 59 years, continues to fall. Overall, deaths from liver disease have soared by 40 per cent in the past decade and continue to rise.
In contrast to the dialysis offered to patients with end-stage kidney disease, as yet there is no technology or treatment available to support patients with liver failure for an extended period. Over the past 50 years, transplant techniques and outcomes have greatly improved, and 5-year survival rates of 70–80% mean transplantation has become the mainstay of treatment for an increasing number of patients with chronic liver disease, metabolic disorders, acute liver failure and malignancy. As such, the demand for donor livers greatly exceeds supply and approximately 20% of patients die (40% of high-risk patients) whilst awaiting transplantation.
The shortage of suitable donor livers is not a problem restricted to the United Kingdom. The shortfall is reflected across other countries to the extent that a patient is now more likely to die within the first 12 months of being listed than the first 12 months post-transplant. Over the past decade there has been a very modest increase in the use of standard or ‘ideal’ organ donors (those retrieved following a diagnosis of brain-stem death (DBD)) and so to respond to this deficit, centres have utilised donors following circulatory death (DCD) and sub-optimal ‘marginal’ donors (those of older age, livers with a presence of high levels of fat or ‘steatosis’).
A rising proportion of transplants are carried out using these ‘marginal’ or ‘extended criteria’ grafts, procured from obese or elderly donors with multiple co-morbidities. These livers are associated with an increased risk of graft failure and recipient morbidity and mortality. Because of the risks associated with their use, in 2014/15, from 1,282 potential solid organ donors, only 924 (72.1%) livers were deemed suitable for retrieval from the donor and 812 (63.3%) were subsequently transplanted (NHS Blood and Transplant Activity Report 2014/15).
The current standard of donor liver preservation is based on the principle of static cold storage (SCS); that is to say, organs are flushed with cold preservation fluid and transported on ice to the potential recipient's hospital.
Bretschneider and Starzl were the first to attempt to use a machine to preserve a liver in the late 1960's. Over the last 15 years, improvements in technology have enabled machines to come to market that effectively replicate the conditions an organ would experience in the body. These devices pump blood and other medications around the organ at normal blood pressure and allow the user to assess the function of the organ prior to transplantation. Groundbreaking research at The University of Birmingham and The Queen Elizabeth Hospital, part of University Hospitals Birmingham NHS Foundation Trust, saw the world's first transplant of a liver previously rejected for transplantation, after a period of testing on one of these devices.
A successful pilot study followed, and the team were successful in their subsequent application for a Wellcome Trust Grant to set up a larger trial called the VITTAL trial (viability testing and transplantation of marginal livers). The aim of the trial was to enable the use of livers deemed too high risk to use using normal practice, by testing their function prior to transplantation. The trial finished in February and the results are eagerly awaited later this year. This technique, normothermic machine perfusion, has also been shown to be beneficial for usable organs when it is used instead of cold storage, and the European-wide Consortium for Organ Preservation in Europe trial was highlighted in April in the prestigious medical journal Nature.
In the next 5 years, the use of these devices will likely be widespread for most types of transplantable organ and with it will hopefully come further improvements in organ quality, utilization and most importantly, patient outcomes.
Mr Richard Laing
Wellcome Trust Research Fellow at the University of Birmingham and Specialist Registrar in General Surgery at the University Hospitals Birmingham NHS Foundation Trust