March 26, 2025

expert reaction to study on first genetically modified pig-to-human liver transplantation

A study published in Nature looks at a genetically modified pig-to-human liver xenotransplantation.

Prof Peter Friend, Professor of Transplantation, University of Oxford, said:

“This is an important study because it advances the field of xenotransplantation from non-human primates to human, enabling assessment of transgenic xenografts in the context of human immunological and physiological systems.

“This is a very elegant surgical technique which allows the insertion of a (relatively small) xeno-liver with limited disruption to the anatomy of the existing liver (i.e. it is potentially feasible in a clinical setting as a temporary bridging technique).

“The genetic modifications are similar (although not identical) to those used in the recently reported heart and kidney clinical xeno-transplants, and also the xeno-liver cross-circulation studies performed at the University of Pennsylvania.

“The presence of the brain-dead donor’s native liver means that we cannot extrapolate the extent to which this xenograft would have supported a patient in liver failure. However, this study does demonstrate that these genetic modifications allow the liver to avoid hyperacute rejection and (significantly) that the thrombocytopenia associated with liver xenotransplantation is self-limiting, with the platelet count recovering within 7 days. The mechanism of this phenomenon is not fully understood.

“Although the maintenance of normal coagulation parameters (e.g. INR) is reassuring, because the clotting factors produced by the xenograft were not measured directly, the data do not definitively prove that this is a function of the xenograft rather than the native liver.”

Comments provided by our friends at SMC Spain:

Rafael Matesanz, creator and founder of the National Transplant Organisation (Spain), said:

“A frequent approach in the development of xenotransplants of different organs, before moving on to the clinical phase, is to perform them in patients in brain death but with haemodynamic stability, so that the evolution of the organ and the impact on the deceased person’s organism can be assessed at least in the short term, but with circulation maintained.

“At least three kidney transplants have been performed in the United States since 2021 – one with up to 61 days of follow-up in brain-dead patients – and two heart transplants, which served to accumulate a number of useful lessons. In both modalities, they preceded the first clinical experiences in living people, which so far have resulted in two heart transplants (both deceased) and four kidney transplants, two of which have survived after several months of evolution.

“The team at the Xi’an Military Hospital in China has had extensive experience in experimental transplantation of all types of organs from pigs to monkeys for more than a decade. This is the world’s first case of a transplant of a genetically modified pig liver into a brain-dead human. The ultimate goal of the experiment was not to achieve a standard liver transplant, but to serve as a ‘bridge organ’ in cases of acute liver failure, while awaiting a human organ for a definitive transplant. The experience lasted 10 days and the porcine organ remained in good condition, with acceptable basic metabolic function and no signs of acute rejection, indicating that the procedure was successful for its intended purpose and could be used in vivo in the near future.

“In short, this is an important experiment, which opens up a different path to what has been tried so far in both vital organs (heart) and non-vital organs (kidney), such as the temporary replacement of the diseased liver until a human liver can be obtained for the definitive transplant’.”

Iván Fernández Vega, Professor of Pathological Anatomy at the University of Oviedo (Spain), Scientific Director of the Principality of Asturias Biobank (BioPA) and Coordinator of the Organoid hub of the ISCIII Biomodels and Biobanks Platform, said:

“I found the work very relevant, but we have to be cautious. The study represents a milestone in the history of liver xenotransplantation, describing for the first time a transplantation of a genetically modified porcine liver into a human being (in this case, a brain-dead human).The quality of the work is very high, both in terms of scientific rigour and the exhaustive clinical, immunological, histological and haemodynamic characterisation of the procedure. Sophisticated genetic modifications have been applied to the graft to prevent hyperacute rejection, one of the most critical complications in preclinical models of xenotransplantation.

“The clinical implications are highly relevant, as optimising this approach could expand the pool of available organs and save lives in liver emergencies. This work complements and extends the existing evidence on previous pig-to-human heart and kidney xenotransplantation. It provides several relevant novelties:

• It is the first study to demonstrate that a genetically modified porcine liver can survive and exert basic metabolic functions (albumin and bile production) in the human body.
• It shows that there was no major coagulation dysfunction, in contrast to what was observed in other models, such as the first human cardiac xenotransplantation, where microthrombi and severe disorders were detected.
• He points out the need to assess possible myocardial damage in early postoperative phases, given the early elevation of AST and cardiac enzymes, which can be confused with liver damage.
• The use of xenograft as a bridging therapy is proposed, especially in patients with acute liver failure awaiting a human graft, although not as a definitive solution, as bile and albumin production was limited for long-term support.

“However, the study has relevant limitations:

• A major limitation of the study is that it is a single case (n=1), which precludes drawing generalisable conclusions or establishing robust patterns of clinical and immunological response. Although this is a pioneering advance, studies with a larger sample and in living recipients will be necessary to confirm the safety, efficacy and reproducibility of the procedure.
• Limited duration of follow-up (10 days), by decision of the recipient’s family, which prevents assessment of medium- and long-term viability of the graft. Therefore, it does not add information in relation to acute and chronic rejection of xenotransplantation.
• Only basic liver functions (albumin synthesis and bile secretion) were assessed, with no data on other complex liver functions such as drug metabolism, detoxification or immune function.
• The heterotopic helper transplantation procedure would not allow resection of the original liver, which invalidates it as a strategy for example in patients with hepatocarcinoma awaiting transplantation.”

‘Gene-modified pig-to-human liver xenotransplantation’ by Wang et al. was published in Nature at 16:00 UK time on Wednesday 26th March.

DOI: 10.1038/s41586-025-08799-1

Declared interests

Iván Fernández Vega “He declares that he has no conflicts of interest.”

Prof Peter Friend: “Please note I have an association with OrganOx Ltd, a spin-out company from the University of Oxford: I am a co-founder and Chief Medical Officer. OrganOx manufactures a liver perfusion device for use in liver transplantation (the OrganOx metra); this is being adapted for potential use in liver support using extra-corporeal liver perfusion. OrganOx is now working in collaboration with eGenesis, the University of Pennsylvania and the University of Oxford to test the use of genetically-modified pigs as a source of organs for extra-corporeal liver support.”

For all other experts, no reply to our request for DOIs was received.