Consistent Liver Function Support from Gene-Edited Pigs to Non-Human Primate Acute Liver Failure Models via Extracorporeal Liver Cross-Circulation

Abstract Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are severe, rapidly progressing conditions. Existing non-biological artificial liver support has limited efficacy, and liver transplantation is constrained by donor shortage and the time window. Extracorporeal liver cross-circulation (ELC) using gene-edited (GE) pigs offers a promising bridging therapy. Here, six Tibetan macaque ALF models were connected via ELC to 8GE pig livers under normothermic machine perfusion for 74–144 h to assess feasibility and functional support. Basic vital signs of the recipients, including heart rate, body temperature, and mean arterial pressure, remained relatively stable. Their AST/ALT rose then declined, total bilirubin trended upward, albumin and total protein remained stable, and bile secretion was continuous, indicating effective replacement of impaired liver function. INR and fibrinogen remained relatively stable, while platelets dropped sharply and stayed low, suggesting generally maintainable coagulation but thrombocytopenia. Complement, immunoglobulins, and B/T/NK cells remained low, indicating good immunosuppression. Donor liver injury was mainly ischemia/reperfusion- and inflammation-mediated, without typical hyperacute or acute rejection. In summary, 8GE pig livers under room-temperature ex vivo cross-perfusion maintained stable vital signs in ALF recipients, supported liver function for >72 h in all six recipients (up to 144 h), and effectively avoided hyperacute and acute rejection, providing a feasible strategy and key data for the safety and efficacy of clinical ELC.