First pig liver transplant in the world that the human body does not reject

BarcelonaThe first documented interspecies transplant (xenotransplant) in the world dates back 120 years, but it wasn't until a few decades ago that it was seriously tested to become a therapeutic option for humans. Pigs are the most commonly used animal to test the procedure, among other reasons, so that their organs are similar in size to those of humans. Until now They have been made from heart and kidney, but it is one of the most complex medical procedures in existence and the current survival rate is really low. But the scientific community does not stop: a team of researchers from China has made the first genetically modified pig liver graft, with six altered genes to prevent rejection, in a brain-dead person. The procedure was performed last year, and this Wednesday the journal Nature has published its evaluation. To put it simply, the review confirms that the human body did not reject the organ and that it survived and functioned virtually normally for 10 days after surgery.

According to the authors, who work at the Xi'an Military Hospital, an institution with extensive experience in experimental organ transplants of all kinds from pigs to monkeys, the results of the unprecedented operation shed light on the potential for pig liver transplants to become a therapy. bridge: that is, to use it in patients with life-threatening liver failure while they are on the waiting list for a given organ. The goal is ambitious, but it responds to a growing challenge: the shortage of donors, which is particularly affecting the United States. In this scenario, scientists want organs from genetically modified pigs to be proposed as a preliminary step to grafting to extend patient survival. For now, however, the surgery has been performed on people who are brain dead in order to assess, at least in the short term, the development of the organ and the impact on the body of the person who is already dead but whose body continues to function.

After transplanting a portion of a pig liver, the researchers—led by Hai-Long Dong, Lin Wang, and Ke-Feng Dou—monitored the function of the grafted liver, the blood supply to the organ, and the immune and inflammatory responses for 10 days. In this regard, according to the study, just two hours after blood recirculated through the liver (now in the human body), it produced bile and, subsequently, albumin and enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, the immune response was controlled with immunosuppressants. "Blood flow velocity in the porcine hepatic artery and in the portal and hepatic veins remained at an acceptable level. Although the platelet count decreased soon after surgery, it eventually returned to normal levels," the study notes.

According to Oxford University transplant professor Peter Friend, this is an important study because it advances the field of xenotransplantation from non-human primates to humans. He describes the technique as "very elegant" and demonstrates that the six genetic modifications made to the porcine organ prevent the human body from rejecting it. However, he acknowledges that the brain-dead recipient's native liver does not allow for determining the extent to which the donor would function autonomously in the event of liver failure.

Few cases in Spain

According to Beatriz Domínguez-Gil, director of the Spanish National Transplant Organization (ONT), the experiment—or "proof of concept"—demonstrates three key elements: the functioning of the organ within a foreign body, the intact maintenance of the vessels (which prevents thrombotic events), and the fact that the graft does not go to the graft itself. For Rafael Matesanz, founder of the ONT, this is an important experiment, opening up a different path to that tested so far in both vital organs (heart) and non-vital organs (kidney), such as the temporary replacement of a diseased liver until a human liver is obtained for the definitive transplant.

In statements to SMC, Matesanz assesses that the porcine organ remained "in good condition, with an acceptable basic metabolic function and without signs of acute rejection", indicating that the procedure was satisfactory for the purposes pursued and could be used. in vivo in the near future. The expert recalls that, in Spain, the team at the Virgen de la Arrixaca Hospital in Murcia also has experience in pig-to-monkey liver transplants dating back to the last century and is preparing a clinical trial, still pending the corresponding approvals, to transplant genetically modified pig livers from the University of Munich. This would be performed on patients with poor clinical progress and in whom the transplantable organ did not appear within two days, maintaining the porcine organ until the patient is stabilized and a suitable human liver is obtained.

However, it is true that in Spain, acute liver failure (due to toxic agents or indication for retransplantation in the first few days after surgery) only occurred on 111 occasions last year, and of these, in only eight cases (7%) was a suitable liver not found in time. "This means that the situation being treated with this type of transplant is not common, although it cannot be said to be exceptional," Matesanz asserts, who also points out that a patient with acute liver failure has absolute national priority on the waiting list.