Kaishan Tao, Zhaoxu Yang, Xuan Zhang, Hongtao Zhang, Zhibin Lin, Shuqiang Yue, Yanling Yang, Wenjie Song, Desheng Wang, Zhengcai Liu, Haimin Li, Yong Chen, Jingshi Zhou, Rui Ding, Shiren Sun, Ming Yu, Jipeng Li, Weixun Duan, Zhe Wang, Jingwen Wang, Jiayun Liu, Minwen Zheng, Xijing Zhang, Wen Yin, Weijun Qin, Dongmei Bian, Lin Li, Min Li, Hao Xu, Dan Wei, Hong Zhang, Li Zhang, Quancheng Wang, Juanli Duan, Zhihong Lu, Hailong Dong, Dengke Pan, Lin Wang, Kefeng Dou
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.