Gene-Edited Pig Liver Survives 11 Days in Brain-Dead Human Recipient

In a milestone that pushes xenotransplantation closer to the clinic, a surgical team at Xijing Hospital of the Fourth Military Medical University in Xi’an, China, has transplanted a liver from a six-gene-edited pig into a brain-dead human recipient, replacing the native liver in its normal anatomical position. The xenograft functioned for the full 11-day observation period, producing albumin and bile with normal composition, albeit at relatively low levels, while the recipient’s circulation remained haemodynamically stable throughout. The study, published in Nature Biomedical Engineering, is among the most rigorous assessments yet of whether a pig liver can perform the daunting metabolic, synthetic and biliary duties of a human liver inside a human body, and it offers an unusually detailed map of both the promise and the persistent immunological obstacles that stand in the way.

The liver has long been considered the most difficult organ to transplant across species. Unlike the heart or kidney, whose failures can be bridged by dialysis or mechanical support, the liver performs hundreds of interlocking tasks: synthesising clotting factors and albumin, clearing toxins and ammonia, producing bile, and orchestrating immune surveillance through its unique sinusoidal vasculature. Previous pig-to-human attempts relied on auxiliary transplantation, in which the pig liver was added alongside the recipient’s own liver rather than replacing it, providing partial metabolic support without fully testing the xenograft’s capacity. Earlier work, including a 2024 case in which a gene-edited pig liver supported a patient for ten days, and a 2025 report of gene-modified pig-to-human liver xenotransplantation by the same Chinese group, demonstrated feasibility but left open the question of whether an orthotopic graft, placed where the human liver once sat, could sustain life-sustaining function on its own.

Central to the new study was the donor animal itself. The team used a pig engineered with six genetic modifications, or 6-GE, designed to blunt the three-pronged human immune attack on pig tissue. Three genes were knocked out: GGTA1, CMAH and B4GALNT2, which encode enzymes that decorate pig cell surfaces with carbohydrate antigens, including the galactose-alpha-1,3-galactose epitope, N-glycolylneuraminic acid and the Sd(a)-like antigen, against which humans carry preformed natural antibodies. Three human genes were added: CD46 and CD55, which regulate complement activation at the cell surface, and thrombomodulin (THBD), an anticoagulant protein that helps convert protein C to its activated form and dampens the inflammatory coagulation cascade. Polymerase chain reaction and Sanger sequencing confirmed the edits at the genomic level, and screening found no evidence of porcine endogenous retrovirus transmission or microchimerism in the recipient’s tissues during the observation window.

The recipient was a brain-dead individual, a model that allows researchers to evaluate xenograft function under genuine human physiology while respecting the ethical framework of organ donation. Brain death, however, is a double-edged sword: the dying brain triggers a storm of systemic inflammation and endothelial injury that can itself destabilise haemodynamics and complicate interpretation of graft outcomes. The surgical team performed the orthotopic transplant, removing the native liver and connecting the pig organ to the recipient’s portal vein, hepatic artery, hepatic veins and biliary system. Preoperative ultrasound confirmed that the diameters of the donor and recipient portal veins and hepatic arteries were compatible, a practical prerequisite that is far from trivial given the size and anatomical variability of both human and porcine vasculature.

Over 11 days of continuous monitoring, the xenograft demonstrated that a pig liver can execute core hepatic functions in a human host. The graft produced albumin continuously and generated bile with normal composition, findings that indicate functioning hepatocytes and an intact biliary epithelium, even though the absolute quantities remained below what a healthy human liver would deliver. Metabolomic analyses, deposited in a public database under accession OMIX017282, tracked the biochemical interplay between graft and host. Systemic haemodynamic stability was maintained throughout, meaning the recipient did not require escalating vasopressor support attributable to graft failure, and the pig liver did not provoke the catastrophic collapse that has historically accompanied cross-species organ transplants.

Yet the study is equally notable for what went wrong, and the authors are candid about it. Imaging and functional assessment revealed suboptimal hepatic perfusion arising from microthrombosis, the formation of microscopic clots within the graft’s sinusoidal vessels, which the researchers believe contributed substantially to the late-phase decline in hepatic function. Coagulation abnormalities emerged as progressive thrombocytopenia, a falling platelet count, alongside reduced activity of clotting factors. This pattern echoes the thrombocytopenia and coagulation dysregulation seen in pig-to-baboon liver transplants and in the landmark pig-to-human heart transplants, and it points to a fundamental incompatibility between pig endothelium and the human coagulation system that current genetic engineering has only partially resolved. The liver’s consumption of platelets and clotting factors, combined with impaired thrombomodulin-mediated protein C activation in the face of endothelial stress, appears to drive a vicious cycle of microvascular clotting and bleeding risk.

The immunological portrait drawn from histopathology was in some respects encouraging. Examination of biopsy and autopsy tissue found scant infiltration by T cells and B cells and minimal deposition of immunoglobulin G, suggesting that the adaptive immune response, the arm of immunity responsible for chronic cellular rejection, was largely held in check by the genetic modifications and the targeted immunosuppressive regimen. Instead, the dominant pathology was innate: prominent activation of innate immune cells and evidence of immunoglobulin M-mediated complement activation, the rapid, antibody-triggered cascade that has historically destroyed unmodified pig organs within minutes. That the classical hyperacute rejection was avoided, while a slower innate-driven injury emerged, marks a shift in the nature of the problem rather than its elimination.

The authors argue that these findings define the research agenda for the next phase of clinical translation. Endothelial damage, microthrombosis and coagulopathy now stand out as the critical challenges, and addressing them will likely require additional genetic modifications, such as further human anticoagulant and complement-regulatory transgenes, together with refined immunosuppressive protocols tailored to the liver’s distinctive immunology. The study also underscores the value of the brain-dead recipient model, which generates clinically relevant data without exposing a living patient to an unproven therapy, even as it cautions that the inflammatory milieu of brain death may exaggerate some forms of injury. Metabolomics, serial histology and comprehensive coagulation profiling of the kind reported here give transplant teams a granular, time-resolved picture of how a xenograft fails, information that no animal model can fully replicate.

For the field at large, the experiment represents a careful step forward rather than a breakthrough cure. Global shortages of donor livers leave millions of patients with end-stage liver disease facing limited options, and pig organs, which can be gene-edited, pathogen-screened and produced on demand, remain the most credible long-term solution. The demonstration that a six-gene-edited pig liver can sustain albumin and bile production and haemodynamic stability for 11 days in a human body, while the precise mechanisms of its gradual functional decline are documented at molecular resolution, converts xenogeneic liver transplantation from a speculative concept into an engineering problem with identifiable targets. Whether the next iteration of gene-edited donors and immunosuppressive strategies can extend graft survival from days to months, and ultimately to the years a clinical therapy would demand, will be decided by the coagulation and innate immune pathways this study has now brought into sharp focus.

Subject of Research: Orthotopic xenotransplantation of a six-gene-edited pig liver into a brain-dead human recipient

Article Title: Orthotopic liver xenotransplantation from gene-modified pig to decedent human

Article References: Tao, K., Yang, Z., Zhang, X., Zhang, H., Lin, Z., Yue, S., Yang, Y., Song, W., Wang, D., Liu, Z., Li, H., Chen, Y., Zhou, J., Ding, R., Sun, S., Yu, M., Li, J., Duan, W., Wang, Z., … Dou, K. (2026). Orthotopic liver xenotransplantation from gene-modified pig to decedent human. Nature Biomedical Engineering. https://doi.org/10.1038/s41551-026-01797-2

Image Credits: AI Generated

DOI: 10.1038/s41551-026-01797-2

Keywords: xenotransplantation, pig liver transplant, gene-edited pigs, orthotopic liver transplantation, brain-dead recipient, microthrombosis, coagulopathy, complement activation, thrombocytopenia, albumin production, bile production, organ shortage