V. de Meijer

What is the best method of liver perfusion?

There is still a shortage of donor livers for transplantation. Unfortunately, not all available donor livers are suitable for transplantation. To make more livers available for use, various techniques have been developed to keep donor livers in the best possible condition after donation. The UMCG, LUMC, and Erasmus MC are launching a nationwide study to jointly investigate which of the two most commonly used techniques works best.

In both techniques, the liver is connected to a machine that supplies the organ with oxygen and nutrients. This treatment is called perfusion. It can be performed in two ways: either blood flow to the liver is restored immediately after the donor’s death while the liver is still in the body, or the liver is first removed from the body, transported, and then in the receiving hospital connected to the perfusionmachine.

The researchers are comparing the two techniques to determine which works best and whether this approach can make more donor livers suitable for transplantation. It is the first study in the world to directly compare the two methods for preserving donor livers.

The joint study is led by Vincent de Meijer (UMCG), Volkert Huurman (LUMC), and Jeroen de Jonge (Erasmus MC).

In or Outside the Body

The main difference between the two techniques is the timing of when a donor liver is reoxygenated. In one method, this occurs shortly after death, while the organs are still inside the donor’s body (in situ normothermic regional perfusion, NRP). This minimizes further damage caused by oxygen deprivation. This is similar to a heart attack or stroke: the faster blood flow is restored, the more tissue is preserved.

In the other method, the liver is first removed and transported to the transplant center. Only there is the organ connected to a perfusionmachine that mimics blood circulation (ex situ perfusion). This treatment may limit or partially repair damage caused during the period of oxygen deprivation. Both techniques are beneficial for liver quality, at least better than without machine perfusion.

De Meijer: “In countries such as France, Italy, and Spain, donor organs are often already being re-perfused with oxygen-rich blood while still inside the donor’s body after death. There, this has now become the standard approach. In the Netherlands, both this method and the treatment of organs outside the body are reimbursed and practiced. Remarkably, the approach involving treatment within the donor’s body has never been investigated in a large, randomized study. Precisely because both treatments are available in the Netherlands and are considered standard of care, we can now compare them thoroughly for the first time.”

Study Hopefully Leads to More Available Livers

To determine which approach ultimately works best, the researchers are examining various outcomes. First, they are examining how well the liver functions after transplantation. In doing so, they are paying particular attention to bile duct damage: damage to the small channels in the liver that drain bile toward the intestine. This is a common problem that significantly impacts the patient’s recovery. Less damage means that doctors can use more donor livers and that patients experience fewer complications.

In addition, the study examines the environmental impact and the effects on other organs, such as the kidneys and the pancreas. These organs are also supplied with oxygen during donor perfusion.

Equal Collaboration Among Three Centers

The collaboration among the three transplant centers is a key component of the study. Not only are the researchers working closely together, but so are the five Independent Retrieval Teams that retrieve donor organs throughout the Netherlands. The principal investigators therefore refer to this as a joint effort: “We’re doing this as a single national team. Each center is on an equal footing. By pooling our knowledge and experience, we can conduct this research together.”

The study has begun on October 1. Over the course of five years, the researchers aim to perform more than 500 liver transplants as part of the study. For this study, the consortium (INSPIRE) received a grant of €947,000 from ZonMw’s “Passende Zorg” framework program. In addition, the Ministry of Health, Welfare, and Sport and the Dutch Healthcare Institute have provided support, ensuring that both treatments are part of standard care in the Netherlands.