Pig livers could serve as potential bridge to liver transplants

Success of first part of Penn Medicine study is significant for those facing liver failure.

January 19, 2024

5 Min Read
Penn Medicine

Across the country, more than 10,000 patients are waiting for liver transplants, and some patients run out of time waiting for a new organ. Initial results from a research study at the Perelman School of Medicine at the University of Pennsylvania marked a milestone in the quest for a more effective option to “bridge” critically ill patients to liver transplant. The research team has announced the first successful completion of an experiment to circulate a recently deceased donor’s blood through a genetically engineered pig liver outside their body – an effort they plan to study further in hopes of providing options to save more patients from dying while waiting for transplants.

The study was made possible through the generosity of a donor family seeking to help other families through advancement of important clinical research. During the experimental procedure, which took place in December, the donor’s circulatory system and breathing were maintained after examinations determined they had experienced brain death and their organs were not suitable to be donated to others. The donor’s own liver was kept in place, while a porcine liver was connected to the body using blood-carrying tubes to evaluate its potential to serve as a perfusion vehicle. The porcine liver showed no signs of liver inflammation during the 72-hour study period, while the donor’s body remained physiologically very stable. The research team says the initial results – which will be followed by refining the procedure on an additional three deceased donors – shows promise for those with liver disease.

“Any time a patient dies while waiting for a transplant, it is a tragedy, and we are always working to develop new ways to extend their lives,” said Abraham Shaked, MD, PhD, of the Penn Transplant Institute and the Eldridge L. Eliason Professor of Surgery, who leads the study. “The success of the first part of our study is significant for those facing liver failure, offering a glimpse into a future where innovative solutions can bring hope to patients who might otherwise be destined to die while waiting for a transplant."

Each year in the United States, more than 330,000 people require treatment for liver failure. Currently, transplantation is the only definitive cure, and unlike patients with heart or kidney failure, there are no mechanical options available to replace the functions of diseased livers prior to transplant. Among the thousands awaiting a new liver, waits can stretch to as long as five years. The researchers say that if the new approach proves safe and feasible, it could serve as a bridge to transplant for the sickest patients for a short time before a human liver becomes available for transplantation.

The experimental approach, called extracorporeal perfusion, involved circulating the patient’s blood through a genetically engineered pig liver outside the body using an extra corporeal liver cross-circulation device made by OrganOx, Inc. The study employs a unique pig liver developed by eGenesis, which has been genetically engineered to deter rejection and improve compatibility with humans, building on findings from a previous study with porcine kidneys. The Gift of Life Donor Program is also a key partner in the ongoing study, which is called PERFUSE-2, working closely with donor families and medical researchers throughout the process. eGenesis is providing funding for the research.

Next, the investigators will study the approach in deceased donors whose own livers have been removed, to determine the feasibility, safety, and effectiveness of using the porcine liver perfusion system in the future as a potential bridge to transplant. They also hope to evaluate the approach for use in patients whose own livers could recover from injury, similar to the use of extracorporeal membrane oxygenation for patients with severe heart and lung illnesses.

Mike Curtis, PhD, president and chief executive officer of eGenesis, expressed sincere appreciation to the deceased patient and their family, underscoring their pivotal role in enabling this step. “We extend our deepest gratitude to the donor and the family of the donor for their profound generosity, which will pave the way for future work toward a potential solution for the many patients in need of life-saving liver support,” he said.

“This milestone event moves us closer to a future where we can offer effective treatments for acute liver decompensation,” said Peter Friend, MD, Chief Medical Officer of OrganOx. “Our system combined with a genetically modified liver combines modern organ perfusion technology with the functions of a whole liver, which is a potentially powerful combination that could save lives.”

“We are proud to have collaborated on this pioneering study that has the potential to bring new hope to liver patients by providing a bridge to transplant or time for healing,” said Richard D. Hasz, Jr., MFS, CPTC, president and CEO of the Gift of Life Donor Program, which played a crucial role in identifying and obtaining consent from the patient’s family to donate their loved one’s body to this groundbreaking project. “This unique study was only possible thanks to the generosity of a donor family willing to help alleviate the suffering of others despite their own personal loss. Every day, we are inspired by the kindness of families who choose donation.”

“Our family is very proud to support this medical advancement and see our loved one’s legacy benefit countless others,” said a member of the donor family. “It is a testament to our loved one’s selflessness and compassion to know this donation offers such hope for people suffering serious disease in the future.”

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