Evidence
Alert

A new technique could make more livers available for transplant

Demand for liver transplants is so high that many people on the waiting list die before they can receive a transplant. But surgeons are rejecting increasing numbers of donated livers because they are not satisfied with the quality. New research could address this problem and make more livers available for transplant.

Current practice is for most organs to be stored in ice after being removed from donor patients. But organs can deteriorate in ice or be judged to be unsuitable for transplant.

Researchers studied a technique called Normothermic Machine Perfusion (NMP). It keeps blood flowing through the liver while it is outside the body. The liver is preserved in a near real-life condition while it is assessed for transplant.

The new trial, called VITTAL, showed that many livers which had been rejected by surgeons could be transplanted successfully into patients. This is a step forward in making more livers available for transplantation.

What’s the issue?

In recent years, more livers are becoming available for transplantation, but they are increasingly from older, more obese, donors. That means the livers are of lower quality and many are rejected by surgeons.

In 2016-17, 240 patients (19%) waiting for liver transplants in the UK either died or were removed from the waiting list.

Liver donations increased markedly between 2008 and 2018. At the same time, the proportion of livers that were rejected almost doubled.

Surgeons are concerned about offering lower quality livers to sicker patients. But these decisions are often based on opinion, not hard fact.

The quality of livers stored in ice can deteriorate between removal from a donor and transplant into the recipient. The NMP technique mimics real life. The donor liver receives oxygenated blood and other nutrients while outside the body. Its condition is preserved and may even improve.

The VITTAL trial looked at livers classed as unsuitable for transplantation by surgeons. It assessed whether the NMP technique could revive livers so they could be offered to patients.

What’s new?

The VITTAL trial was the first to investigate and evaluate NMP for donor livers that were initially discarded. It found that the technique could salvage some of the livers that are currently discarded.

Between November 2016 and February 2018, livers dismissed by surgeons as unusable were assessed. They were transplanted into patients who had been counselled about the high-risk nature of this trial.

During the trial, 185 livers were discarded by surgeons across the UK and offered to the study. Of these, 31 were re-examined and 22 were transplanted into patients.

The study found that:

  • all patients were alive when followed up one year or more later, though some had developed complications
  • by day 542, four patients needed another liver transplant for problems related to the bile duct.

Why is this important?

Keeping livers in a near real-life situation, rather than in ice, may give a better indication of whether they will be successfully transplanted. If they are working well on NMP, they may be more likely to work well in a patient.

Using some of the livers which are currently discarded would add significantly to the number of livers suitable for transplant in the UK. This would help reduce the numbers of patients dying while on the waiting list.

The study has already made a difference. The research team is now using NMP as a clinical tool to assess livers. They are now transplanting some livers that they would previously have thrown away. This means more livers are available to patients. Other UK liver transplant centres are considering a similar move.

What’s next?

During the VITTAL study, livers were only offered to the least sick patients who were most likely to respond well. Another study is underway to assess the use of these “rescued” livers on other patients. The study will include patients on the waiting list who are more unwell, or who are waiting for a second transplant and have limited life expectancy.

Further work is needed to look for markers in blood and perfusion samples which could help predict the outcome of liver transplants using NMP.

All seven UK liver transplant centres have the technology to use this technique. The researchers hope that the trial will help build the experience and confidence to use livers previously regarded as unsuitable for transplant.

You may be interested to read

The full paper: Mirza DF, and others. Transplantation of discarded livers following viability testing with normothermic machine perfusion. Nature Communications, 2020;11:2939

Nasralla D, and others. A randomized trial of normothermic preservation in liver transplantation. Nature, 2018;557;50–56

Porte R, and others. Pretransplant sequential hypo‐ and normothermic machine perfusion of suboptimal livers donated after circulatory death using a hemoglobin‐based oxygen carrier perfusion solution. Am J Transplant, 2019;19(4);1202–1211.

Clavien P-A, and others. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol, 2012; 13(1); e11–e22.

Funding

This study was funded by the Wellcome Trust and Cancer Research UK. It was supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham.

Commentaries

Study author

The advantage of NMP is that it mimics what happens in real life; we are better preserving these organs. We learnt from this study that there is a pool of livers that do very well on the machine, and we were able to predict which livers were suitable for transplantation.

We did 10-11% more liver transplants during the study. It is already making a difference. We are now using the machine as a tool to use livers that previously we would not have used. We are also using some of these livers in sicker patients.

Darius F. Mirza, Professor of Hepatobiliary & Transplant Surgery, QE Hospital & Birmingham Children’s Hospital

Surgeon

The study showed that the NMP technique allowed for the active assessment and real-time evaluation of these previously discarded livers. The approach was associated with excellent 90-day patient survival. However, with a number of patients still experiencing complications – notably bile duct problems – more research is needed.

Nigel Heaton, Professor of Liver Surgery, King’s College Hospital, London

Conflicts of Interest

Three authors of this study have financial links with OrganOx Ltd, which developed NMP. Neither DFM nor NH declare competing interests.