Breakthrough in Xenotransplantation: Genetically Engineered Pig Livers Support Liver Functions in Humans

A groundbreaking study published in the Journal of Hepatology has demonstrated that livers from genetically modified pigs can perform essential hepatic functions in human recipients, marking a significant step forward in xenotransplantation. The research centered around a 71-year-old man suffering from hepatitis B-related cirrhosis and hepatocellular carcinoma, who was not eligible for traditional liver transplant options. Surgeons implanted an auxiliary liver from a specially engineered pig, which had undergone ten gene edits to reduce immune rejection and improve compatibility, including knockouts of xenoantigens and insertion of human transgenes.

Initially, the pig liver functioned effectively, producing bile and synthesizing coagulation factors without signs of rejection. However, on day 38 post-transplant, the patient experienced a complication called xenotransplantation-associated thrombotic microangiopathy (xTMA), linked to immune and coagulation issues. Treatment with the complement inhibitor eculizumab and plasma exchange successfully managed the complication, but the graft was eventually removed after 38 days.

Despite the graft's removal, the patient survived for 171 days, providing valuable insights into the potential and challenges of pig-to-human liver transplants. The case underscores that genetically engineered pig livers can support critical liver functions temporarily and highlights the hurdles, particularly with coagulation regulation and immune response management, that remain before this approach can be widely adopted.

This pioneering trial underscores the urgent need for alternatives to meet the severe organ shortage. Globally, thousands die annually awaiting organ transplants, with millions in China alone suffering from liver failure but only a fraction receiving transplants. Xenotransplantation could serve as a vital solution to bridge the gap between organ demand and supply.

Lead researcher Dr. Beicheng Sun emphasized that this case is a proof-of-concept that genetically modified pig livers have the capacity to function within humans over extended periods, though further research is essential to overcome existing obstacles. Industry experts believe this development marks the beginning of a new era in transplant medicine, potentially offering hope to patients with acute or chronic liver failure, hepatocellular carcinoma, and other conditions requiring transplantation.

This research signifies a major step toward translating xenotransplantation into clinical reality, paving the way for advances in transplant hepatology and organ bioengineering. The study and related editorial highlight both the promise and ethical considerations inherent in this innovative field.