It remains to be seen as to whether xenotransplantation of organs from genetically engineered pigs will be competitive in comparison to the tissue engineering of new organs. Even given the challenges faced to date, it seems likely that xenotransplanation will be a going concern before the manufacture of viable tissue engineered organs. Initial trials in patients volunteers have taken place for the heart and kidney. As the report here illustrates, the last mile of discovery in which pig organs are transplanted into the first volunteers is likely to require as much work and reveal as many unforeseen issues as was the case for the earlier stages of development, in which the need for genetic engineering of the donor pigs was discovered.
The advent of genetically edited porcine-to-human xenotransplantation has predominantly focused on cardiac and renal applications, with no reported cases of porcine-to-human liver xenotransplantation. This study presents the world's first successful genetically modified pig auxiliary liver xenotransplantation in a living human, achieving an unprecedented survival of 171 days, and provides valuable insights into the critical factors influencing the procedure's success.
A genetically modified pig liver, incorporating 10 targeted gene edits, was transplanted as an auxiliary organ into a 71-year-old patient with large hepatocellular carcinoma in the right hepatic lobe, which was initially deemed ineligible for curative resection. Liver function, metabolic, and coagulation markers were closely monitored throughout the perioperative period.
For the first 31 days post-transplant, no hyperacute or acute rejection, infections, or significant complications were observed, and the patient's hepatic and renal functions remained stable. Early postoperative coagulopathy, as indicated by elevated D-dimer and fibrin degradation products, was successfully managed through anticoagulant therapy. However, on postoperative day 38, the auxiliary liver was removed due to xenotransplantation-associated thrombotic microangiopathy (xTMA). Subsequent management with eculizumab and plasma exchange successfully resolved the xTMA. Unfortunately, repeated upper gastrointestinal hemorrhage ultimately led to the patient's death on day 171.
Link: https://doi.org/10.1016/j.jhep.2025.08.044
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