Case report shows functioning genetically engineered pig liver sustains 71-year-old man for 171 days — Evidence Review

A first-in-human case report shows a genetically engineered pig liver can function in a human for several weeks, suggesting a potential solution to organ shortages. Related research in animal models largely supports the feasibility but highlights persistent complications with immune compatibility and coagulation (1, 2, 4, 9).

• Animal studies consistently demonstrate that porcine livers, especially those with targeted genetic modifications, can perform key hepatic functions in primates for days to weeks, but survival is hampered by coagulation disorders and immune-mediated complications (1, 2, 4, 9).
• The new human case extends functional survival beyond that achieved in most non-human primate xenotransplantation models, although similar issues with thrombocytopenia and vascular injury occurred (1, 4, 9).
• Broader xenotransplantation literature, including heart and kidney models, underscores the importance of advanced gene editing and immunosuppression strategies for improving graft survival and minimizing rejection (6, 7, 8, 13).

Study Overview and Key Findings

The ongoing shortage of donor organs for transplantation leads to thousands of deaths each year, particularly among patients with end-stage liver disease. The recent study published in the Journal of Hepatology presents the first documented case of an auxiliary liver xenotransplant from a genetically engineered pig into a living human, aiming to address this gap. This case not only demonstrates the technical feasibility of porcine liver xenotransplantation, but also exposes the clinical and biological hurdles—such as immune complications and coagulation dysregulation—that must be addressed before widespread clinical application.

Property	Value
Organization	First Affiliated Hospital of Anhui Medical University, Hannover Medical School, Sorbonne Université, Hospital Pitié Salpêtrière
Journal Name	Journal of Hepatology
Authors	Beicheng Sun, Heiner Wedemeyer, Vlad Ratziu
Population	71-year-old man with liver disease
Methods	Case Report
Outcome	Function of genetically engineered pig liver in human
Results	Patient survived for 171 days with functioning pig liver graft.

Literature Review: Related Studies

To situate these findings within the broader scientific context, we searched the Consensus database, which includes over 200 million research papers. The following queries guided our literature review:

1. genetically engineered pig liver transplantation
2. xenotransplantation patient survival outcomes
3. animal organ grafts human viability studies

Related Studies: Topic Summary Table

Topic	Key Findings
Can genetically engineered pig livers support life in primates or humans?	- Genetically engineered pig livers can maintain near-normal hepatic function in primates for several days, but survival has been limited by coagulation defects (1, 2, 4, 9). - The first human case demonstrates function for 38 days, aligning with primate data, but removal was required after vascular complications (1, 2, 4, 9).
What are the main medical hurdles to long-term xenotransplant survival?	- Thrombocytopenia and thrombotic microangiopathy are leading causes of graft failure, even with genetic modification (1, 4, 9). - Immune barriers, including both innate and adaptive responses, remain challenging despite advances in gene editing (12, 13).
How does genetic engineering improve xenograft compatibility?	- Deletion of xenoantigens and expression of human transgenes enhance compatibility and reduce hyperacute rejection (2, 8, 13). - Coagulation issues persist, indicating additional genetic or pharmacologic approaches are needed (1, 2, 4, 9).
What is the clinical potential of xenotransplantation for organ shortage?	- Preclinical models suggest genetically engineered pig organs could bridge patients to allotransplantation or serve as long-term replacements (1, 9, 6, 7, 10). - Clinical translation depends on resolving immunological and coagulation barriers (12, 13).

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Can genetically engineered pig livers support life in primates or humans?

The new study provides the first evidence in a living human that a genetically engineered pig liver can perform essential hepatic functions for several weeks. This finding is consistent with preclinical research, mainly in baboons, which shows that porcine liver xenografts can support life and synthesize key proteins, though survival is often limited to under a month due to complications (1, 2, 4, 9).

• In baboon models, functionally adequate pig livers have sustained recipients for 4–29 days, with limitations mostly due to bleeding and thrombocytopenia (1, 2, 4, 9).
• The human case extended survival to 38 days of actual graft function before removal, with the patient surviving 171 days post-transplant ([news article]).
• Both human and animal studies confirm that xenografted livers can produce bile and coagulation factors (1, 2, 9).
• The findings collectively support the technical feasibility of pig liver xenotransplantation but underscore the need for further advances to achieve longer-term survival (1, 2, 4, 9).

What are the main medical hurdles to long-term xenotransplant survival?

Despite genetic engineering, major complications—particularly related to coagulation and immune activation—continue to limit xenograft survival. The new study encountered thrombotic microangiopathy (xTMA), paralleling issues noted in primate studies (1, 4, 9).

• Thrombocytopenia, spontaneous bleeding, and microvascular thrombosis frequently lead to early graft loss in animal models (1, 4, 9).
• In the reported human case, xTMA led to graft removal, mirroring the vascular challenges seen in primate xenotransplantation (1, 9).
• Even with improved immunosuppression and complement inhibition, innate immune activation remains problematic (12, 13).
• Overcoming these barriers is critical for moving from experimental to routine clinical application (12, 13).

How does genetic engineering improve xenograft compatibility?

Multiple studies show that targeted gene editing in donor pigs—such as removing xenoantigens and expressing human regulatory proteins—reduces hyperacute rejection and improves short-term function, but has not yet overcome all host-graft incompatibilities (2, 8, 13).

• Knockout of pig antigens (e.g., α1,3-galactosyltransferase) and addition of human genes (e.g., CD46, thrombomodulin) prevent hyperacute antibody-mediated rejection in primate recipients (2, 13).
• Despite these modifications, non-antibody-mediated issues like platelet activation and coagulation disorders persist (1, 2, 4, 9).
• Ongoing research explores further genetic changes and adjunctive therapies to address these downstream complications (12, 13).
• The new human study used a pig liver with 10 targeted genetic modifications, highlighting the complexity and gradual progress in this field ([news article], 13).

What is the clinical potential of xenotransplantation for organ shortage?

Multiple sources affirm the promise of xenotransplantation to address organ shortages, but emphasize that translation to widespread clinical use will depend on overcoming immunological and physiological challenges (1, 6, 7, 9, 10, 12, 13).

• Genetically modified pig organs have enabled survival for months in non-human primate models of heart and kidney transplantation, and weeks in liver models (6, 7, 9, 10).
• The new human case supports the potential for xenografts to serve as bridges to transplantation or as alternative treatments where human organs are unavailable ([news article], 1, 9).
• Long-term clinical viability requires further advancements in genetic engineering, immunosuppression, and management of host-graft interactions (12, 13).
• Ethical and biosafety considerations, including zoonotic infection risk, must also be addressed (3, 12, 13).

Future Research Questions

Further research is essential to address the persistent challenges of immune rejection, coagulation disorders, and long-term xenograft function. The current study highlights critical unanswered questions that must be addressed before xenotransplantation can become a mainstream clinical option.

Research Question	Relevance
How can genetically engineered pig liver grafts be further modified to prevent coagulation disorders in human recipients?	Coagulation abnormalities, including thrombocytopenia and thrombotic microangiopathy, are leading causes of graft failure in both animal models and the first human case (1, 4, 9).
What immunosuppression regimens optimize pig liver xenograft survival while minimizing infection risk?	Balancing immune suppression and infection risk is crucial, as immune activation drives rejection but over-suppression increases infection and other complications (12, 13, 9).
How long can genetically engineered pig livers function in human recipients without replacement?	The first human case demonstrated 38 days of graft function; longer-term studies are needed to determine the true potential for bridging or permanent replacement (1, 2, 9).
What are the risks of zoonotic infection from porcine liver xenotransplantation?	Preventing the transmission of porcine endogenous retroviruses and other pathogens is a major biosafety concern highlighted in both preclinical and clinical studies (3, 12, 13).
Which patient populations benefit most from pig liver xenotransplantation as a bridge to transplant?	Identifying candidates—such as those with acute-on-chronic liver failure or hepatocellular carcinoma—may help prioritize early clinical applications (9, [news article]).