Orthotopic liver xenotransplantation from gene-modified pig to decedent human.

Abstract

Xenotransplantation offers a critical solution to global organ shortages. Recent reports show that genetically engineered porcine livers can provide auxiliary metabolic support in human recipients and non-human primates. However, orthotopic pig-to-human liver xenotransplantation remained a challenge owing to the liver immunological and physiological complexity. Here we report the orthotopic pig-to-human liver xenotransplantation in a brain-deceased individual. Throughout the 11-day observation period, the xenograft maintains continuous albumin and bile production with normal composition, albeit at a relatively low level. Systemic haemodynamic stability is maintained, although suboptimal hepatic perfusion resulting from microthrombosis occurred, which likely contributed substantially to late-phase hepatic functional decline. Coagulation abnormalities manifest as progressive thrombocytopenia and reduced clotting factor activity. Histopathological analysis reveals scant T/B cell infiltration and immunoglobulin G deposition, yet demonstrates prominent innate immune activation and immunoglobulin M-mediated complement activation. While certain positive indicators emerge, critical challenges including endothelial damage, microthrombosis and coagulopathy remain. This study highlights the importance of genetic engineering and targeted immunosuppressive approaches to advance the clinical translation of xenogeneic liver transplantation.