Xenotransplantation: The Next Surgical Revolution for Acute Liver Failure?

To review the current state of liver xenotransplantation and evaluate emerging strategies using genetically modified porcine organs for the management of acute liver failure.

The shortage of donor organs continues to limit transplantation, with substantial waitlist mortality, especially in acute liver failure. Progress in the last decades has been driven by advances in gene editing and immunomodulation, allowing for clinical solid-organ xenotransplantation trials since 2021, with early kidney and heart experiences demonstrating feasibility. Liver xenotransplantation might be more challenging because of the liver's metabolic, synthetic, and hemodynamic roles.

This review summarizes the development of liver xenotransplantation and focuses on modern approaches using genetically modified pigs. We discuss 2 main liver-directed strategies: extracorporeal liver support using ex vivo perfusion of whole porcine livers and the transplantation of genetically engineered porcine liver for patients with acute liver failure. Practical aspects of organ preservation, transportation, and application of long-term machine perfusion are also discussed.

Recent first clinical applications of genetically modified porcine liver as auxiliary transplants or associated with extracorporeal circulation systems demonstrated preserved function for several days to weeks without evidence of acute rejection, both in deceased and living recipients. These trials suggest technical feasibility and short-term physiological efficacy, while exposing unresolved challenges related to coagulopathy and immunologic injury.

Liver xenotransplantation using genetically modified porcine organs has progressed from experimental concept to early clinical application. Current evidence supports its potential role as a bridging strategy for acute liver failure, although further refinement is needed for broader clinical adoption.