Proof-of-concept published for pig-to-human liver transplant

A peer-reviewed paper reports proof-of-concept that a genome-edited pig liver can successfully support liver function in human patients.

The newly documented transplant took place in May 2024 at the First Affiliated Hospital of Anhui Medical University, China (see BioNews 1241), and has now been published in the Journal of Hepatology. The patient, a 71-year-old man with advanced liver cancer, showed no signs of rejection, infections or complications for the first month after the transplant. The transplanted pig liver functioned effectively, producing bile and synthesising coagulation factors. However, on day 38, it had to be removed due to a transplant-related blood vessel disorder, which was reversed with medication. Nearly six months after the transplantation the patient died from severe internal bleeding.

'This case proves that a genetically engineered pig liver can function in a human for an extended period,' said the hospital's director Professor Sun Beicheng, who led the transplant team. 'It is a pivotal step forward, demonstrating both the promise and the remaining hurdles, particularly regarding coagulation dysregulation and immune complications, that must be overcome.'

Diannan miniature pigs were used for this study, which have similar-sized livers to adult humans. Ten genome alterations were introduced to the pig to prevent organ rejection; these included knockouts (where pig genes were removed or disabled), and the introduction of transgenes (where human genes were added).

Consent was given for the surgery by the patient and his daughter, after all other treatments had failed, and the patient's own liver was close to rupturing. Before the transplant surgery, the patient received a regimen of immunosuppressive drugs.

The liver performs many complex functions, which pose unique challenges for xenotransplantation – compared to hearts or kidneys. Its roles in filtering toxins and producing vital proteins make it more likely to trigger immune reactions. In some cases, transplanted pig livers can mistake the patient's platelets for foreign cells, leading to internal bleeding.

'Scientifically, the case demonstrates that a genetically modified pig liver can engraft, function, and provide synthetic support in a human recipient, at least for several weeks. Clinically, however, the outcome underscores the limitations of current technology, particularly with respect to long-term survival and complications,' Professor Heiner Wedemeyer, from Hannover Medical School, Germany, who was not involved in the study, wrote in an accompanying editorial.

'This operation does not yet open the door to widespread clinical use of pig livers. But it does establish proof-of-concept that such grafts can function in humans,' added Professor Wedemeyer.

In March 2024, a separate team at the Xijing Hospital of the Fourth Military Medical University in Xi'an, China transplanted a genome-edited pig liver into a brain-dead man, which was published in Nature (see BioNews 1283) and in January 2024, a team from the University of Pennsylvania connected a genome-edited pig liver to a brain-dead man using an external machine with tubes to carry blood (see BioNews 1223).