A world first: Successful liver transplantation after 3 days of in vitro storage
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A world first: Successful liver transplantation after 3 days of in vitro storage.
On May 31, the team of Mark W. Tibbitt from the University of Zurich in Switzerland published a research paper entitled Transplantation of a human liver following 3 days of ex situ normothermic preservation in Biotechnology , a sub-journal of Nature .
Image source: Nature Biotechnology
The article reports a case where a human liver , abandoned by all medical centers , was preserved in vitro for 3 days using the “ectopic normothermic perfusion” technique for liver transplantation. One year later, the transplant patient had no health problems, and his liver function and life were normal.
Research contents
Solid organ transplantation, especially liver transplantation, is one of the most influential innovations in modern medicine, restoring a normal quality of life to patients who would otherwise die prematurely, but the lack of available organs remains the most important factor limiting transplant success.
There is a growing gap between the need for liver transplants and the small number of liver transplants available.
Donor livers prior to transplantation are typically stored on ice for no more than 12 hours, as liver viability decreases proportionally beyond this time.
Therefore, the number of organs that can be matched with transplant recipients is very limited, and some donors’ livers that can be used for transplantation have to be wasted.
Currently, ectopic perfusion techniques have been introduced to prolong the duration of safe preservation and improve graft quality.
Despite these advances, extending the total ex vivo time of human organs remains a serious limitation.
The first clinical success reported here opens new horizons for clinical research and promises to extend the time window for liver transplantation to 10 days to assess the viability of donor organs and convert urgent and demanding surgery to elective surgery.
Liver donor source
On May 19, 2021, investigators obtained a liver graft from a 29-year-old female donor with invasive abdominal desmoidosis, a disease associated with chronic intra-abdominal abscesses and recurrent episodes due to multidrug-resistant bacteria sepsis is related, so long-term combination medication and total parenteral nutrition are required.
In addition, there was a 4 cm tumor of unknown nature in segment 1 of the liver. The investigators performed cold flushing with Institute Georges Lopez 1 (IGL-1) solution to remove the liver according to standard purchasing protocols.
This potential source of liver transplantation was rejected by all other medical centers because the donor had persistent sepsis, contained multidrug-resistant microorganisms, and required diagnostic testing for liver lesions.
Ectopic normothermic perfusion
The researchers used a technique called “ex situ normothermic perfusion” to preserve human livers outside the body for three days.
With this machine, an organ can be supplied with a normothermic blood substitute outside the body. The liver is placed in a sterile environment, maintained at a temperature of 37°C, to simulate the human environment, providing the liver with a pump to replace the heart, as well as some hormones and nutrients.
Specifically, the researchers attached liver grafts to a Wyss perfusion device and performed normothermic (37°C) ectopic perfusion after a brief refrigeration period of 4 hours.
Includes a low-flow cold (6-8°C) oxygenated perfusion (HOPE) period of 2 hours and 40 minutes to allow passage of all vessels portal vein (PV), hepatic artery (HA) and inferior vena cava (VCI) and common bile duct (CBD) intubation in preparation for transplantation.
After priming the Wyss machine with a blood-based but leukocyte-free perfusate, targeting a hematocrit of 28 to 30%, supplemented with freshly prepared platelets and additives, began perfusing the liver graft.
At the same time, broad-spectrum antibacterial drugs are used in the perfusion to reduce the potential infection of the graft by bacteria and fungi present in the donor.
Liver transplant
On May 22, 2021, livers were transplanted into patients with several severe liver diseases, including advanced cirrhosis and severe portal hypertension.
Biopsy performed 60 minutes after reperfusion showed no evidence of reperfusion injury and no areas of necrosis.
Importantly, the intrahepatic bile ducts appear to be well preserved.
No reperfusion syndrome (hemodynamic instability) was observed, which is associated with engraftment of the injured graft.
Postoperative situation
After transplantation, the investigators observed that the transplanted liver functioned normally, with only a very low degree of graft damage.
Serum bilirubin levels, a specific hepatic coagulation factor V, remained below 50% for 36 hours, returning to normal only on postoperative day 4.
During the first six weeks after transplantation, only a basic immunosuppressive regimen is required.
The patient quickly returned to quality of life without any signs of liver damage, such as bile duct rejection or damage, and remained healthy a year after surgery.
Summary
This study is the first to use the “ectopic normothermic perfusion” technique to preserve the transplanted liver donors in vitro for 3 days, and the liver transplants were successfully performed, and the transplanted patients remained healthy one year later.
As liver transplantation remains one of the most challenging and resource-intensive surgical procedures available today, as an unscheduled emergency procedure, this technique may enable such surgery to be an elective procedure, possibly allowing several days in advance Schedule surgeries while increasing the number of livers available for transplant, saving more lives.
The success of using the “ectopic normothermic perfusion” technique for the first time to preserve the liver for a long time can open up new horizons for the treatment of many liver diseases.
These results suggest that this technique may not only increase the number of potential donor organs available, but also enhance the prospect of treating donor organs with drugs before transplantation.
However, the researchers say this still requires longer observation of a larger number of patients for further study.
references:
Clavien, PA., Dutkowski, P., Mueller, M. et al. Transplantation of a human liver following 3 days of ex situ normothermic preservation. Nat Biotechnol (2022). https://doi.org/10.1038/s41587-022 -01354-7
A world first: Successful liver transplantation after 3 days of in vitro storage
(source:internet, reference only)
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