Liver xenotransplantation: Progress, mechanistic barriers and strategies for clinical translation.

Pig-to-human liver xenotransplantation holds promise for alleviating the severe shortage of human donor livers. In recent years, China has achieved milestone progress in this field. Livers from gene-edited pigs have been successfully transplanted into brain-dead human recipients and a living patient with advanced hepatocellular carcinoma. These advancements demonstrate that a combination of genetic engineering and immunosuppressive protocols can effectively mitigate xenogeneic immune rejection. Furthermore, the transplanted porcine livers were able to perform key liver-specific physiological functions in the recipient, including synthesis, metabolism, secretion, and detoxification. These findings suggest that porcine livers may provide a critical window for patients with acute liver failure, serving as a bridge to allotransplantation or enabling native liver regeneration. However, due to the liver's complex physiological and metabolic functions, significant challenges remain in the post-transplantation phase. These include acute humoral xenograft rejection, coagulation dysregulation, and incompatibility of functional proteins across species. These factors currently limit the survival time of porcine livers in human recipients. This review summarized the latest advances and existing challenges in liver transplantation and discussed the impact of strategies such as genetic engineering, perioperative management, and immunosuppressive regimens on the long-term survival of transplant recipients, thereby providing a reference for promoting the long-term survival and clinical translation of liver xenotransplantation.