A milestone in liver xenotransplantation: The first 10-gene-edited pig-to-living-human auxiliary transplantation and the road ahead

The global shortage of human donor livers poses a formidable barrier to treating end-stage liver diseases and unresectable hepatic malignancies, leaving millions of patients without life-saving options each year. While genetically engineered pig-to-human xenotransplantation has achieved significant breakthroughs in cardiac and renal fields, liver xenotransplantation has long lagged due to the liver’s intricate metabolic, synthetic, and immunological functions. The recent report by Zhang et al. in the Journal of Hepatology —documenting the world’s first successful auxiliary liver xenotransplantation from a 10-gene-edited pig to a living human, with the recipient surviving 171 days—marks a transformative milestone in regenerative medicine. This commentary examines the study’s groundbreaking contributions to donor genetic engineering and perioperative clinical management, while critically analyzing the persistent challenge of xenotransplantation-associated thrombotic microangiopathy and outlining future directions to advance clinical translation.