In China, for the first time in the history of medicine, a genetically modified pig liver was successfully transplanted into a living human and took over key organ functions for almost six months. This was an auxiliary xenotransplantation of the liver – a procedure in which the pig organ does not completely replace the human liver but complements it – and the result of this pioneering procedure was described in detail in a professional study published in the esteemed journal Journal of Hepatology. This case is already being hailed as a breakthrough in transplant hepatology and an important step towards a new generation of solutions for the global organ shortage crisis.

The background of this story lies in stubborn statistics: worldwide, tens of thousands of people receive a new liver annually, but hundreds of thousands remain without a transplant that could potentially save their lives. In China, hundreds of thousands of cases of severe liver failure are estimated annually, while in 2022, only about 6,000 liver transplants from human donors were performed. In the global order, the liver accounts for only a part of approximately 157 thousand transplanted solid organs annually, and the number of candidates for transplantation is manifold greater. That is precisely why the concept of using genetically engineered pig organs as a "backup warehouse" for human patients is gaining more and more importance.

Patient whose life was extended by a pig liver for 171 days

At the center of the published study is a 71-year-old man with hepatitis B, liver cirrhosis, and hepatocellular carcinoma (HCC). Due to the combination of advanced chronic disease and tumor, he was not a candidate for classic liver resection nor did he meet the criteria for human liver transplantation. In other words – according to current protocols and available human organs, therapeutic options were approaching their end in his case.

The research team from the First Affiliated Hospital of Anhui University therefore decided to apply an experimental approach: a genetically modified pig liver was surgically implanted as an auxiliary organ, while retaining the patient's own liver. This concept of auxiliary liver transplantation had been previously applied with human organs – for example in acute liver failure – but never before with a xenograft, i.e., an organ from another species. The pig liver was connected to the main blood vessels, ensuring blood flow and the possibility to take over part of the metabolic and synthetic load.

The goal was not permanent organ replacement, but proof that a highly modified pig liver can stably function in the human organism long enough to reduce the burden of disease, pull the patient out of the acutely dangerous phase, and provide time for eventual additional therapeutic steps. In this sense, it is a concept of a "bridge" – a biological device that bridges the period in which the human organism is most endangered.

Ten genetic modifications: from removing pig antigens to incorporating human genes

The transplanted liver originated from a specially bred Diannan mini-pig, developed in collaboration with a team from Yunnan Agricultural University. The donor animal underwent thorough screening for pathogens, and the organ was created by applying multiple gene modifications. The researchers performed a total of ten key changes: three pig genes responsible for creating the so-called xenogeneic antigens (molecules on the cell surface that the human immune system recognizes as highly foreign) were "knocked out", while seven human genes were inserted to improve immunological and coagulation compatibility.

Among the genes that were switched off are those responsible for creating specific sugar structures on the surface of pig cells, which in humans cause a rapid, so-called hyperacute rejection reaction. The aim was to prevent what was once the main reason for the rapid failure of the xenograft – an immediate immune attack as soon as the organ comes into contact with human blood. At the same time, genes for human complement regulatory proteins (e.g., CD46, CD55, CD59), which dampen the exaggerated immune system response, and genes for molecules involved in the fine-tuning of blood clotting and the interaction of the endothelium with the immune system (EPCR, CD47, and others) were inserted.

In practice, such a combination of a genetically modified profile creates an organ that, from an immunological point of view, behaves less "piggy" and more "neutral" in relation to the human organism. Researchers designed the liver to simultaneously reduce the risk of rejection and avoid uncontrolled coagulation disorders, which were previously one of the most severe problems in preclinical models of pig-to-human liver transplantation.

The first month: regular organ function without signs of acute rejection

After the operation, the team closely monitored the patient through laboratory parameters, clinical picture, and imaging tests. In the first 31 days, neither hyperacute nor classic acute rejection reaction was recorded. Renal function remained stable, and liver parameters – such as bilirubin levels, enzymes, and coagulation factors – suggested that the pig liver was indeed taking over and performing a significant part of the metabolic load.

One of the key indicators of liver function is bile production. In this patient, the pig liver continuously secreted bile, and concentrations of protein molecules produced by the organ, such as certain clotting factors, could be measured in the blood. Clinically, this meant that the xenograft was not just a passive "attachment," but a functional organ that actively participated in the regulation of metabolism and hemostasis.

At the same time, the patient received strong, but specifically combined immunosuppressive therapy to suppress the potential attack of T lymphocytes and antibodies on the foreign organ. The regimen was designed to maintain an acceptable balance between preventing rejection and minimizing the risk of infections, which are always a serious threat in such radical transplantation procedures.

Dangerous trap: thrombotic microangiopathy and removal of the pig liver

Although the first phase after the procedure looked encouraging, signals appeared early that the coagulation system was extremely sensitive. Laboratory findings showed elevated values of D-dimer and fibrin degradation products, indicating activated clotting and enhanced fibrinolysis. The clinical team initially managed to control this with anticoagulant therapy, but the condition became increasingly complex over time.

Around the fifth week after the operation, a clear picture of xenotransplantation-associated thrombotic microangiopathy (xTMA) developed. This is a disorder in which microthrombi form at the level of small blood vessels, along with mechanical damage to blood cells, consumption of platelets, and risk of multiorgan failure. In this patient, doctors assessed that further retention of the pig liver was too risky, and the xenograft was surgically removed on the 38th day.

After the organ removal, therapy with eculizumab was introduced, a biological drug that blocks complement and is often used precisely for severe forms of thrombotic microangiopathies. In combination with plasma exchanges (plasmapheresis), the treatment led to the resolution of xTMA, and coagulation and hemolysis parameters gradually improved. This confirmed that the problem was primarily related to the interaction between the pig liver and the human immune system, and not an irreversible generalized damage.

Life after xenograft removal and tragic outcome

Although the pig liver was removed relatively early, its period of active function provided several crucial weeks during which the patient was metabolically stable. After the organ removal, the team continued to treat him according to standard oncological and hepatological protocols, but his underlying disease remained extremely severe. The combination of cirrhosis, tumor, and previous aggressive transplantation therapy significantly weakened the body's reserves.

The patient ultimately died on the 171st day after transplantation due to repeated episodes of severe bleeding from the upper digestive tract. In patients with cirrhosis and portal hypertension, such bleedings, especially from esophageal and gastric varices, are unfortunately not uncommon and often carry high mortality. In this case, despite everything, the pig liver played an important role in extending life and provided extremely valuable insight into the limits and possibilities of xenotransplantation.

The authors emphasize that the outcome was not unexpected at any point in terms of the global prognosis – the patient had multiple high-risk factors and would have faced very limited survival without any transplantation. However, the fact that the genetically modified pig liver functioned in his body for almost a month and a half, and extended his life by a total of almost half a year, shows that the concept of an auxiliary xenograft can be clinically feasible.

How this case fits into the broader story of xenotransplantation

World interest in xenotransplantation has sharply increased in recent years. After a series of successful transplants of genetically modified pig kidneys and hearts, the research focus is increasingly turning to the liver – an organ that performs dozens of different functions and whose failure rapidly leads to a fatal outcome. Unlike kidney patients, who can bridge the period until transplantation with dialysis, patients with acute or acute-on-chronic liver failure often do not have a long-term sustainable "replacement" technology.

In the spring of 2025, the first description of genetically modified pig liver transplantation into a brain-dead recipient was published in the journal Nature. In that case, the organ functioned for about ten days, producing bile and liver proteins, without signs of hyperacute rejection. Although it was an experiment on a patient who had already died according to neurological criteria, the study proved that a pig liver can maintain basic functions in the human body in real time, and not just in laboratory models.

The new case published in the Journal of Hepatology goes a step further: it is the first documented example in which a pig liver was implanted into a living patient, who subsequently continued to function daily, eat, communicate with family, and go through standard postoperative rehabilitation. It is precisely this transition – from brain-dead donors to living recipients – that marks the beginning of a new phase of research, where the key question is no longer just "can the organ work," but also "how will its work affect the human long-term."

Potential for patients with acute liver failure and unresectable carcinoma

The authors of the study, as well as the journal editors in the accompanying editorial comment, see the most potential precisely in the so-called "bridging" scenarios. These are situations where a patient has a sudden deterioration of liver function – for example due to acute hepatitis, worsening existing cirrhosis, or an aggressive tumor – and a human organ is not immediately available or the patient currently does not meet the strict criteria for transplantation.

In such cases, a genetically modified pig liver could, at least theoretically, temporarily take over part of the function, reduce the toxic load on the organism, and buy several weeks or months. During this period, the patient could be stabilized, additional oncological or hepatological treatments could be performed, and perhaps even brought into a state where they would become a candidate for human liver transplantation. A similar principle has already been seen in xenotransplantations of pig kidneys, where organs sometimes serve as a transitional solution until donor transplantation.

Another potential application relates to patients with large liver tumors that initially cannot be surgically removed. If an auxiliary pig organ took over the majority of the function, surgeons would have greater freedom in more aggressive resections of the primary liver, and even in combination with local oncological methods such as ablation, transarterial chemoembolization, or targeted radiotherapy. However, such scenarios remain hypothetical for now and require rigorous testing before any wider application.

Ethical, safety, and regulatory dilemmas

Even with impressive technical results, xenotransplantation remains a field burdened with a series of open questions. One of the most frequently mentioned is the risk of transferring hidden pig viruses – including endogenous retroviruses – into the human population. Although donor animals undergo extensive screening, and modern gene-edited pig strains are further designed to reduce this risk, regulatory bodies will require long-term monitoring and strict protocols before allowing the routine application of such organs.

Another question is long-term immunosuppression. Patients with pig organs would likely have to receive more complex and intensive combinations of drugs than classic transplant patients, which increases vulnerability to infections and malignant diseases. In this specific case, the patient was already severely oncologically and hepatologically compromised, so it is difficult to separate how much the late outcome is a consequence of the xenotransplantation itself, and how much is due to the underlying disease and the total therapeutic burden.

There is also the ethical dimension of candidate selection: who should receive a pig organ – those for whom classic transplantation is unavailable, or precisely the most promising candidates? If it turns out that pig organs can function long-term, will pressure emerge to offer them as a standard option, perhaps even before we exhaust all possibilities of human donation? There are no simple answers to these questions for now, so further development will depend on a combination of medical data, social consensus, and regulatory frameworks.

What follows: from individual cases to clinical trials

Currently, the medical community is in a transitional phase: individual case studies and small series of procedures show that pig-to-human organ transplantation is technically feasible, but still far from routine practice. The authors of the paper in the Journal of Hepatology emphasize that their primary goal was to collect data on short-term liver function, immune interactions, and complications such as xTMA, and not to demonstrate a perfect long-term solution.

The next steps include more precise clarification of the mechanisms leading to thrombotic microangiopathy and other complications, optimization of gene modification combinations in donor pigs, and fine-tuning of immunosuppression and anticoagulation protocols. It will likely be necessary to conduct additional tests in animal models before regulatory bodies approve a larger number of clinical procedures on humans.

In parallel, global transplantation registries and professional societies are closely monitoring the development of xenotransplantation to timely define standards for monitoring, reporting, and informed consent. As the number of solid organ transplants worldwide continuously grows, but demand outstrips supply even faster, the pressure to develop alternative organ sources will become increasingly greater. The case of the 71-year-old patient from China with a genetically modified pig liver is therefore less of an "exotic experiment" and more of an early look into the potential future of transplant medicine.