Clavien and fellow researcher Philipp Dutkowski during the transplantation. (USZ)

Organ Transplant Breakthrough Shows Human Liver Can Survive Outside The Body For Days

1 JUNE 2022

When a donor organ becomes available to someone in need of a transplant, medical personnel need to act quickly. It only takes a few hours for expanding ice crystals to damage delicate tissue, leaving a window of less than 12 hours to assess, transport, and implant the new organ.

 

This not only creates a tremendous time crunch to perform a delicate procedure, but leaves many organs unviable for transplantation.

But a new breakthrough could vastly improve the landscape of liver transplantation: Scientists kept a liver preserved for three days, in non-frozen conditions, before transplanting it into a patient.

Moreover, that liver had been deemed unviable by transplant centers, since it had a tumor and came from a patient with sepsis (bacterial infection) that needed to be assessed and treated. The three-day window allowed the researchers to perform these actions, clearing the liver for transplant.

A year later, the recipient was perfectly healthy, with normal liver function and a normal quality of life. Although further investigation is necessary ahead of widespread clinical uptake, the results could mean, in the future, an increase in the number of livers deemed viable for transplantation.

"The success of liver transplantation over the past 30 years has led to a worldwide shortage of organs … the lack of available organs remains the single most important factor limiting the success of transplantation," writes a team of researchers led by surgeon Pierre-Alain Clavien of University Hospital Zurich and Wyss Zurich in Switzerland.

"This inaugural clinical success opens new horizons in clinical research and promises an extended time window of up to 10 days for assessment of viability of donor organs as well as converting an urgent and highly demanding surgery into an elective procedure."

 

Note: there's a graphic image of the organ below, so don't scroll further if you don't want to see it.

The technique the team used to preserve the liver is one that has been gaining increasing traction in the medical world.

It's called ex situ (off site) normothermic perfusion, and the principle is simple. An organ is placed in a sterile environment and maintained at a temperature of 37 degrees Celsius, around normal human body temperature ("normothermic").

In this environment, it's constantly flushed with fluids mimicking human body functions, such as nutrients, hormones, and blood. In 2020, Wyss Zurich demonstrated the efficacy of their perfusion technology by keeping a human liver functioning normally for seven days outside of the body.

human liver ex vivo perfusionThe donor liver in the perfusion bath. (Clavien et al., Nature Biotechnology, 2022)

On 19 May 2021, their research took a massive step forward. They were offered a liver graft from a 29-year-old woman suffering invasive abdominal tumors and abscesses, as well as recurrent sepsis from antibiotic resistant bacteria.

The liver itself had a tumor of an unknown nature, which would have required a diagnostic work-up before the organ could be deemed suitable for transplantation.

 

On the other side, there was the recipient: a 62-year-old man suffering from advanced cirrhosis, severe portal hypertension, and multiple and recurrent liver cancer.

He was fully informed of the experimental nature of the procedure, and agreed to the risks, not least because his conditions were so advanced that he had a near-zero chance of receiving a liver transplant in time via the normal transplant lists.

On 22 May 2021, on the beginning of the fourth day after the donor organ was recovered, the transplant procedure took place. The procedure was a complicated one, requiring a team of engineers, biologists, and physicians all working together.

And it was a success, a resounding one: There was absolutely no sign of the damage that can occur, known as reperfusion injury, when blood returns to tissue after a period of no blood supply at all.

The result was comparable, the researchers said, to living donation, when an organ graft is extracted from a willing living donor and transplanted directly into the recipient.

The only intervention required was the basic, standard regime of immunosuppression for six weeks, to avoid the recipient's body rejecting the donor organ. The transplanted liver functioned normally, and showed no adverse effects – no signs of rejection, or injury to the bile ducts, which is common.

 

A year later, he was still doing well. In all, it's a wonderful and highly promising result.

"As liver transplantation remains one of the most challenging and resource-intensive surgical procedures currently performed as an urgent procedure out of regular schedule, long-term ex situ perfusion could enable such surgeries to become an elective procedure, like living donation," the researchers say.

"We think that this first transplantation success with an ex situ normothermic perfusion preserved organ can open new horizons in the treatment of many liver disorders."

The research has been published in Nature Biotechnology.