Surgeons performing a pig liver transplant at the First Affiliated Hospital of Anhui Medical University, China, in May 2024
Xianfu Lu
Utilizing organs from pigs for transplants in humans could potentially transform medical practices, offering a solution that might save numerous lives currently lost waiting for organ transplants. Previous research has already led to successful transplants of pig hearts and kidneys, and now, for the first time, a pig liver has been transplanted into a living human.
“This is exceptionally groundbreaking,” declares Heiner Wedemeyer from Hannover Medical School in Germany, who was not part of the operation. “The patient was critically ill prior to the transplant, but lived for an additional six months as a result of the surgery.”
The complexity of the liver has made previous attempts at similar surgeries only feasible in brain-dead patients, demonstrating some success. “The heart merely serves as a muscle to pump blood,” says Wedemeyer. “The kidney is relatively straightforward as its role revolves around filtration. However, the liver is distinct, as it synthesizes various proteins essential for multiple metabolic functions.”
Transplants of pig hearts and kidneys in living patients have shown initial promise, yet complications have occurred later on. For instance, one heart transplant was linked to the potential transmission of a pig virus, which resulted in the patient’s demise.
Recently, Beicheng Sun and colleagues at Anhui Medical University conducted a pig liver transplant on a 71-year-old man. The patient’s liver was deemed unsuitable for a standard transplant due to significant scarring and a large tumor stemming from a hepatitis B infection. Each liver transplant procedure must be cautiously considered, as thousands die annually while waiting for one, according to Sun.
Despite the risks, the man needed a transplant, as his tumor could have ruptured fatally at any moment. With the patient’s consent, in May 2024, Sun’s team substituted the right segment of his liver, which harbored the tumor, with a portion from an 11-month-old miniature pig. The operation, lasting five hours, involved linking the pig’s liver blood vessels to the existing vessels on the left side of the recipient’s liver.
To inhibit the liver’s rejection by the recipient’s immune system, they deactivated three genes in the pig and introduced seven new genes so that the organ mimicked human physiology more closely. In addition, the recipient was prescribed immunosuppressive medications, and the team rigorously ensured the liver was free of porcine viruses.
Remarkably, the liver exhibited immediate signs of function by secreting bile, a substance necessary for fat digestion. In a matter of weeks, the patient’s bile and albumin levels—albumin being a protein produced by the liver that prevents fluid leakage from blood vessels—returned to healthy ranges, according to Sun.
However, approximately a month post-transplant, the patient faced severe blood clots, necessitating the removal of the transplant. This was likely triggered by an excessive immune response and abnormal levels of blood-clotting proteins typically regulated by healthy livers. Given the differences between pig and human physiology, such phenomena are more probable with pig organ transplants, notes Sun.
The patient managed to survive for another five months on just his left liver, but ultimately succumbed to stomach bleeding—a condition that frequently accompanies liver scarring, per Sun. Both he and Wedemeyer concur that the bleeding was likely unrelated to the transplant.
In spite of the patient’s passing, the procedure can be viewed as a partial triumph, as he likely would have died soon after his tumor’s removal. Notably, during the period the transplant functioned optimally, the patient’s own liver partially regenerated, contributing to his survival for several months following the transplant’s removal, Wedemeyer notes.
This advancement enhances our grasp of xenotransplantation and suggests that pig livers may provide an interim solution for individuals awaiting human transplants. There’s even a possibility that residual liver tissue could regenerate sufficiently that patients might evade needing further procedures, Sun adds.
Nevertheless, it may take a decade or more before pig livers can effectively replace human organs, according to Sun, emphasizing the urgent necessity to lessen the risk of complications, potentially through additional genetic alterations.
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