ObjectiveTo systematically review the research progress, key challenges, and clinical translation prospects of xenogeneic liver transplantation in alleviating donor shortage. MethodBy searching and reviewing relevant literature from domestic and international sources, the current status of xenogeneic liver transplantation research was summarized, focusing on immunological barriers, the development of genetically engineered donor pigs, coagulation dysfunction, physiological compatibility, preclinical studies, and perioperative management strategies. ResultsThe use of multigene-edited pigs has largely overcome hyperacute rejection, with research focus shifting to acute humoral rejection, cellular rejection, and severe coagulation dysfunction resulting from interspecies molecular incompatibility. The combination of genetically engineered donor pigs, novel immunosuppressive regimens centered on anti-CD40 monoclonal antibodies, and refined perioperative management has significantly prolonged graft survival in non-human primate models. ConclusionsXenogeneic liver transplantation offers a promising avenue to address the donor liver shortage. Preclinical studies have preliminarily confirmed its feasibility; however, challenges such as coagulation disorders and physiological incompatibility remain. Future efforts should integrate multigene-modified donors with precise immunomodulation and cross-species physiological support to facilitate clinical translation.
