Could removing fat from donor livers help save more lives?

The liver transplant team at the Royal Free Hospital (RFH) has successfully recruited the first liver to be used in a revolutionary new study, supported by CRN North Thames, looking at whether fat can be removed from donor livers to make them suitable for transplantation.

Liver disease is currently the third leading cause of premature death in the UK and once patients reach the final stages of the disease, transplantation is the only potential cure. However, because there is a shortage of suitable donor organs, not everyone who needs a transplant can receive one.

Currently a third of all donated livers which are declined for transplants are discarded due to the presence of fat within the liver cells – known as non-alchoholic fatty liver disease (NAFLD).

This is because fatty livers do not tolerate being stored and transported in an icebox and are therefore not likely to result in a successful transplantation.

However, the DeFat study, led by Professor Peter Friend at the University of Oxford, is aiming to understand whether an innovative ‘defatting’ strategy for livers will make fatty livers more suitable for transplantation.

As part of the trial, the livers will be preserved on a machine in very similar conditions to those in the body (termed normothermic machine perfusion; NMP). A combination of currently available drugs are used to release fat from the liver cells and the fat is removed from the perfusion machine using a specialised filter. This reduces the amount of fat in the liver and improves its function.

The trial involves the random assignment of 60 livers from donors with a high risk of fatty liver disease to either NMP alone or NMP with fat removal treatment. The study will then assess how many of these livers are safe to transplant and, in those that are then transplanted, follow the outcomes after the operation.

The main objective is to show whether this treatment is safe; it is also hoped it will help to design a future, larger study which will test the extent to which fat removal actually leads to additional transplants.

There are no anticipated side effects or risks related to the preservation and defatting process itself on the machine as all defatting agents are flushed from the liver before transplantation.

The trial is being led by Professor Joerg-Matthias Pollok and Mr. David Nasralla at the RFH. After recruiting the first liver, Professor Pollok said: “This is a potentially ground-breaking study for people waiting for a liver transplant as it might enable us to significantly increase the number of livers which are suitable for transplantation in the future.

“As obesity rates in the population are on the rise, we are seeing more livers with NAFLD in the donor pool which unfortunately we currently have to reject for donation. We will continue to support the study as suitable livers become available and we look forward to assessing the results and what this could mean for our patients awaiting transplant going forward.”