IN A WORLD-FIRST, Chinese surgeons have transplanted a 10-gene-edited pig liver into a living human as an auxiliary graft, demonstrating that a porcine liver can support human metabolism for weeks and function as a bridge in otherwise inoperable liver cancer.
The 71-year-old man had hepatitis B–related cirrhosis and a massive hepatocellular carcinoma in the right lobe that made standard resection or human liver transplantation impossible. After rapid clinical deterioration and lack of donor options, the multidisciplinary team proceeded under compassionate use with an auxiliary porcine liver xenotransplant on 17 May 2024, following resection of the tumour-bearing right lobe.
Engeneering the Gene-Edited Pig Liver
The donor Diannan miniature pig had 10 precise genetic modifications: knockout of key xenoantigen genes and knock-in of seven human genes to improve immune and coagulation compatibility. Post-reperfusion, the graft produced bile immediately and contributed measurably to metabolism, bile acid synthesis, albumin production and coagulation factor generation. Early liver and kidney function remained stable, and no hyperacute or acute rejection was detected on serial biopsies and immunological assessment.
However, the case also exposed a major barrier to clinical xenotransplantation. Around one month after surgery, the patient developed xenotransplantation-associated thrombotic microangiopathy (xTMA), with hemolysis, thrombocytopenia, complement activation and microvascular thrombosis.
Despite anticoagulation, eculizumab and plasma exchange, the team ultimately removed the pig graft on day 38. The patient’s native left liver, which had hypertrophied, maintained sufficient function, and xTMA resolved. The patient later suffered recurrent variceal upper gastrointestinal bleeding and died on postoperative day 171.
Future Opportunities and Ongoing Limitations
Investigators conclude that auxiliary pig-to-human liver xenotransplantation is technically feasible and can provide meaningful hepatic support, but xTMA, coagulation incompatibility and complement activation remain major obstacles. The case sets a clinical benchmark for future trials and underscores the need for further gene editing, refined immunosuppression and targeted strategies to prevent xTMA if xenoliver support is to move into broader clinical use.
Reference
Zhang W et al. Genetically engineered pig-to-human liver xenotransplantation. J Hepatol. 2025;DOI:10.1016/j.jhep.2025.08.044.
