Successful Transplant with Damaged Human Liver

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Liver transplant
The surgeon, Prof. Pierre-Alain Clavien, and the patient when the latter was discharged from hospital after the successful transplantation. Credit: USZ

In a world’s-first, doctors have successfully conducted a transplant with a damaged liver kept outside the body for 3 days.

In May 2021, a multidisciplinary team in Zurich conducted the world’s first successful liver transplant using a damaged human liver. Using a machine, the damaged liver was kept outside the body for 3 days before being transplanted into a cancer patient. A year later, the team published their study in the journal Nature Biotechnology.

The 62-year-old recipient patient suffered from severe portal hypertension, advanced cirrhosis, and recurrent hepatocellular carcinoma. Although the patient was on the Swiss transplant waiting list, he had a low chance of receiving an organ in time. Therefore, the team of researchers offered him a treated human liver.

According to the study, within the first week of receiving the graft, the patient suffered only minimal graft injury. Moreover, after just 4 days of the transplant, he experienced a full liver function recovery with a return to normal INR (international normalized ratio) levels. Twelve days after the transplant, the patient was discharged on a reduced immunosuppressive regimen. Furthermore, he returned to his usual daily activities within 2 months. At his one-year follow-up, doctors did not report any signs of rejection or injury to the bile ducts.

I am very grateful for the life-saving organ. Due to my rapidly progressing tumor, I had little chance of getting a liver from the waiting list within a reasonable period of time.

Transplant recipient

The study authors report that such recovery and a low degree of reperfusion injury is only observed in living donations. That is when livers from healthy donors are transplanted immediately in recipients. This is the first successful transplantation with an ex-situ normothermic perfusion preserved organ.

Damaged to Healthy in 3 Days

The 29-year-old transplant donor suffered from invasive abdominal desmoid fibromatosis with chronic intra-abdominal abscesses, recurrent sepsis due to multi-resistant bacteria, and a tumor in one segment of the liver. As a result, multiple centers discarded the liver due to its poor quality. However, the multidisciplinary Zurich research team decided to treat the damaged liver with their ‘ex-situ normothermic preservation’ machine. And after just 3 days of treatment, the liver returned to a healthy, transplant-able state.

Researchers from the University Hospital Zurich, ETH Zurich, Wyss Zurich and the University of Zurich developed the perfusion machine. The team first demonstrated its use in 2020. Using their newly developed machine, they were able to keep the liver outside the body for a week. However, none of the organs underwent transplants into other human beings.

The machine works like the human body, providing the liver with ideal conditions. Along with maintaining a normal body temperature, the machine pumps oxygenated blood through the organ with the help of an oxygenator and a replacement heart. A dialysis unit helps perform the kidney’s functions to keep the organ live and functioning. Moreover, the machine allows infusion of nutrients and hormones to mimic the function of the pancreas and intestine. Thus, helping the damaged liver return to a healthy state.

While the organ is receiving perfusion outside the body, researchers can administer antibiotics and other drugs, and conduct laboratory and tissue tests.

Our therapy shows that by treating livers in the perfusion machine, it is possible to alleviate the lack of functioning human organs and save live.

Professor Pierre-Alain Clavien, director of the Department of Visceral Surgery and Transplantation at the University Hospital Zurich

According to study authors, it is possible to keep livers functioning and alive, outside the body, for longer than 3 days.

Future of Liver Transplants

The demand for liver transplants has significantly increased over the years. This has further widened the gap between organ availability and organ demand. Moreover, currently available perfusion machines and conventional practices of storing organs on ice can only keep transplant organs viable for 12 hours. Thus, providing a very short window for transport, evaluation, and implantation of a donor graft. And further limiting the organ availability.

Approximately 75% of cirrhosis patients receive a diagnosis at an advanced stage when it’s too late for treatment and a liver transplant is their only option. However, due to an organ shortage, many die while waiting. According to global statistics, 22 people die each day while on a transplant waiting list. Thus, the perfusion machine can alleviate this shortage by improving the functioning of diseased or damaged organs. And ultimately saving lives.

The interdisciplinary approach to solving complex biomedical challenges embodied in this project is the future of medicine. This will allow us to use new findings even more quickly for treating patients.

Professor Mark Tibbitt, professor of macromolecular engineering at ETH Zurich

This is not the first time that doctors have perfused organs outside the body. Previously, researchers have used the Organ Care System to perfuse the heart and lungs outside the body.

Reference:

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

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