First-of-Its-Kind Pig-to-Human Liver Xenotransplant Marks Milestone in Organ Engineering and Transplant Medicine

In a landmark advance for transplant science, researchers in China have reported the world’s first successful auxiliary liver xenotransplantation from a genetically engineered pig to a living human recipient. The procedure, conducted on a 71-year-old patient with inoperable liver cancer and end-stage hepatic failure, resulted in graft functionality for over a month and patient survival for 171 days—offering a compelling proof-of-concept for cross-species liver transplantation.

The transplanted porcine liver, engineered with 10 targeted gene edits, demonstrated metabolically active bile secretion, albumin production, and coagulation support. It was intended as a bridging therapy for liver function stabilization following resection of a massive hepatocellular carcinoma in a patient who was not a candidate for conventional liver transplant. Importantly, this auxiliary transplantation preserved the patient’s native left liver, which gradually regenerated postoperatively. For the first 31 days, the pig graft functioned without signs of hyperacute or acute rejection.

Histological analysis revealed minimal lymphocytic infiltration and complement activation, and serial imaging confirmed stable graft perfusion and bile drainage. Serum markers confirmed active liver metabolism, including rising human and porcine bile acids and albumin levels. Additionally, porcine coagulation factors were robustly secreted, with Factor VIII levels far exceeding those of human baseline.

Despite promising early function, the patient developed xenotransplantation-associated thrombotic microangiopathy (xTMA) by postoperative day 31—a severe, often fatal complication involving microvascular thrombosis and complement activation. Elevated D-dimer, schistocytes, sC5b-9, and myocardial injury markers supported the diagnosis. Despite plasma exchange and eculizumab therapy, graft removal became necessary on day 38. Pathology confirmed widespread complement deposition and fibrinous thrombi within the pig liver vasculature.

Following graft removal, the patient's native liver sustained hepatic function, aided by continued immunomodulation and monitoring. Unfortunately, on day 135, the patient developed recurrent upper gastrointestinal bleeding due to gastric varices and died from hemorrhagic shock on day 171. The case offers multiple firsts in the field of xenotransplantation: the first gene-edited pig liver transplanted into a living human, the first use of an auxiliary model for in vivo hepatic support, and the first detailed clinical documentation of xTMA in a xenograft recipient. It also underscores the persistent immunologic and hematologic challenges, particularly in the liver’s complex vascular and synthetic environment.

This genetically edited liver included knockouts of three xenoantigen genes (GGTA1, CMAH, and B4GalNT2) and insertion of seven human genes promoting immune tolerance and coagulation compatibility (including hCD46, hCD55, hCD59, hCD39, hTBM, hEPCR, and hCD47). The pigs were bred in pathogen-free conditions and rigorously screened for zoonotic viruses, including porcine endogenous retroviruses (PERVs), with no evidence of viral transmission postoperatively. Unlike previous pig liver studies—conducted in brain-dead humans or non-human primates—this study demonstrated sustained metabolic support in a living recipient. The auxiliary approach allowed continuous in vivo assessment of rejection, coagulopathy, and organ compatibility, offering a vital platform for future xenotransplant research.

Yet the case also highlights key obstacles. Platelet consumption, coagulation dysregulation, and complement overactivation remain major risks. The graft secreted supraphysiologic levels of porcine coagulation factors, including FVIII, possibly contributing to endothelial stress. Furthermore, species-specific incompatibilities in von Willebrand Factor and Glycoprotein Ib interactions may have driven platelet loss and thrombotic complications.

Future strategies will likely require next-generation genetic modifications—targeting coagulation regulation, endothelial interaction, and complement pathways—as well as tailored immunosuppression and anticoagulation regimens. Importantly, this study suggests that even short-term xenograft support can bridge patients to recovery or subsequent allograft transplantation.

With organ shortages claiming thousands of lives annually, auxiliary xenotransplantation from genetically engineered pigs offers a promising pathway forward. While technical and ethical challenges remain, this historic case sets the stage for early clinical trials and broader consideration of cross-species organ support as a viable therapeutic avenue in transplant medicine.