They successfully transplant a liver discarded by hospitals, 'repaired' in three days and preserved without using cold

They successfully transplant a liver discarded by hospitals, 'repaired' in three days and preserved without using cold

Losing a liver for a transplant because it is in poor condition at the time of donation, or because it has exceeded the 12 hours in which they are usually kept, is a real catastrophe for the patient and family members who anxiously await that saving organ. 12 hours is, until now, the approximate maximum period for which the organ can be used. That is why the information you have just published is so relevant Nature Biotechnology. According to this scientific journal, a Franco-Swiss team has managed to multiply the conservation period of a liver –up to three days and without the need for cold–, which also allows real progress: that organs that were previously discarded receive treatment while they remain outside of a human body and then become suitable for transplantation.

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A year has passed since a patient suffering from various serious liver diseases, including advanced cirrhosis and hypertension in the vessels supplying the organ, received a preserved liver treated for three days outside the human body.

Pierre-Alain Clavien, director of the Department of Visceral Surgery and Transplantation at the University Hospital of Zurich, and his collaborators report in the article that the transplanted liver functioned normally, with minimal injury when blood flow returned to the internal vessels, and that it was only necessary, during the first six weeks after the transplant, the administration of a basic immunosuppressant (a drug that, to prevent rejection, reduces the activity of the immune system).

A 'living' liver connected to a machine

Usually, in the case of the liver, the donated organ is kept in a cold solution between 2°C and 5°C and implanted in a few hours. Most hospitals try to limit that time to less than 12 hours, as liver viability declines proportionately beyond this time frame.

Another preservation technique, which does not require cold, is called “ex situ normothermic perfusion”. It consists of connecting the donated liver to a machine that supplies it (at 37°C and slowly and continuously) with a substance, in this case a blood substitute. The aim of the method is to keep the organ 'alive' to see if it works. In the case of the liver, if it cleanses certain toxic substances.

The novelty announced this Tuesday does not lie in the fact of preserving the organ outside the body, because in previous experiments conservation times of up to 10 days have been achieved; yes: in organs not suitable for transplantation.

Until the publication of today's experiment, the maximum time in which an organ preserved outside a human body could be successfully transplanted was set at 24 hours. But what is really new – in addition to those three days in which the organ was still viable – is what the researchers have done to that liver during those 72 hours in which it has been connected to a machine. Not only have they evaluated if he was fit, they have also given him drugs to cure him and make him viable.

An operation of more than five hours

On May 19, 2021, the research team received an organ from a 29-year-old donor who suffered from various pathologies. Among others, a four-centimeter tumor "of an unclear nature" and an infection with several microorganisms resistant to treatment. The organ, weighing 1.7 kilos, had been discarded by the other health centers "mainly because it required a diagnostic work-up of the liver injury that was not immediately possible and due to the ongoing sepsis", the authors of the study report.

The donor's liver was then connected to a machine made by the Wyss Translational Center in Zurich. An apparatus specially designed by engineers, biochemists and physicians to perform long-term ex situ mechanical perfusions in injured livers. Among other substances, the donated organ was administered "broad-spectrum antimicrobial agents" to mitigate possible infection by bacteria and fungi residing in the donor.

This advance would increase the number of organs that we can use

Luis Rodríguez Bachiller — Member of the Gregorio Marañón Transplant Unit

During the hours that the liver was connected to the machine, all biochemical indicators improved. The danger of the tumor was ruled out and, after consulting with a council made up of international experts, the decision was made to consider the liver suitable for transplantation. The surgery, which lasted five hours and 26 minutes, was performed on May 22, 2021. Within two months, the patient returned to his daily life. One year after the intervention, he remains healthy.

“We will be able to offer the transplant to more people”

Luis Rodríguez Bachiller, head of the normothermic perfusion program at the Transplant Unit of the Gregorio Marañón Hospital in Madrid, highlights the "prestige" of Pierre-Alain Clavien's team and comments for on the advance published today: "Open the door only to evaluate doubtful organs, but also to treat and improve them”.

This specialist reports that, by incorporating increasingly older donors (sometimes over 70 years), it is not uncommon for doubtful organs to arrive, with certain characteristics that may discourage their use for transplants. Among these conditions, for example, is the infiltration of fat in the liver, something common in people with obesity or with an alcohol problem. This means that the organ, once transplanted, does not work: a risk that is avoided by evaluating it beforehand, by connecting it to a machine.

Between 20% and 30% of donated organs, says Dr. Rodríguez Bachiller, are doubtful. Some are usually connected to the perfusion machine to assess their viability. This evaluation process has been carried out for years in the Community of Madrid and in some other centers in the country. Until now, Gregorio Marañón has led eight procedures, of which five have culminated in successful transplants.

By incorporating increasingly older donors (sometimes over 70 years), it is not uncommon for questionable organs to arrive, with certain characteristics that may discourage their use for transplants

If the advance published today is generalized, the evaluation of organs would go on to their treatment and improvement prior to their implantation in the patient. Thus, there would be more viable organs, because some that are discarded today would be used. “That would allow us to increase the number of organs that we can use. We could offer the transplant to more people”, says Rodríguez Bachiller.

This doctor recalls how frustrating it is to discard donated organs because they are not viable, adding to that frustration the emotional toll and the human and economic cost of starting up a machinery for organ donation and conservation that will not be able to be used later.

Both this specialist and the authors of the experiment warn, however, that more research is needed, with more patients and longer observation periods. These results, however, suggest that this technology may not only increase the number of potential donor organs available, but also improve the prospect of treating donor organs with drugs before transplantation.

'Image a': CT scan of the donor's liver showing the tumor of unknown severity (benign/malignant) in segment 1 (arrow). 'Image b': Donor's liver on the stretcher. Portal vein (PV) lavage cannula during infusion. Additional cannulae were placed in the hepatic artery (HA), infrahepatic inferior vena cava (IVC), and common bile duct (CBD or common bile duct). 'Image c': Donor liver during ex situ perfusion with normothermic machine. Cannulae were placed in the PV, HA, iVCI, and CBD. The suprahepatic inferior vena cava (sIVC) was temporarily sutured.

Credit Pierre-Alain Clavien University Hospital Zurich, Switzerland / Nature Biotechnology

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