Stravitz, R. T. & Lee, W. M. Acute liver failure. Lancet 394, 869–881 (2019).
Moreau, R. et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 144, 1426–1437 (2013).
Bernal, W. Liver transplantation for critically ill patients with acute on chronic liver failure: a prospective national programme of waitlist prioritisation. Lancet Reg. Health Eur. 46, 101067 (2024).
Bañares, R. et al. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial. Hepatology 57, 1153–1162 (2013).
Kribben, A. et al. Effects of fractionated plasma separation and adsorption on survival in patients with acute-on-chronic liver failure. Gastroenterology 142, 782–789.e783 (2012).
Agarwal, B. et al. Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on- chronic liver failure. J. Hepatol. 79, 79–92 (2023).
Burke, L. et al. Plasma exchange does not improve overall survival in patients with acute liver failure in a real-world cohort. J. Hepatol. 82, 615–621 (2025).
Thompson, J. et al. Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: a multinational, prospective, controlled, randomized trial. Liver Transpl. 24, 380–393 (2018).
Demetriou, A. A. et al. Prospective, randomized, multicenter, controlled trial of a bioartificial liver in treating acute liver failure. Ann. Surg. 239, 660–670 (2004).
Anand, R. P. et al. Design and testing of a humanized porcine donor for xenotransplantation. Nature 622, 393–401 (2023).
Kim, S. C. et al. Long-term survival of pig-to-rhesus macaque renal xenografts is dependent on CD4 T cell depletion. Am. J. Transplant. 19, 2174–2185 (2019).
Längin, M. et al. Consistent success in life-supporting porcine cardiac xenotransplantation. Nature 564, 430–433 (2018).
Montgomery, R. A. et al. Results of two cases of pig-to-human kidney xenotransplantation. N. Engl. J. Med. 386, 1889–1898 (2022).
Moazami, N. et al. Pig-to-human heart xenotransplantation in two recently deceased human recipients. Nat. Med. 29, 1989–1997 (2023).
Porrett, P. M. et al. First clinical-grade porcine kidney xenotransplant using a human decedent model. Am. J. Transplant. 22, 1037–1053 (2022).
Griffith, B. P. et al. Genetically modified porcine-to-human cardiac xenotransplantation. N. Engl. J. Med. 387, 35–44 (2022).
Kawai, T. et al. Xenotransplantation of a porcine kidney for end-stage kidney disease. N. Engl. J. Med. 392, 1933–1940 (2025).
Shah, J. A. et al. Prolonged survival following pig-to-primate liver xenotransplantation utilizing exogenous coagulation factors and costimulation blockade. Am. J. Transplant. 17, 2178–2185 (2017).
Cross-Najafi, A. A. et al. Current barriers to clinical liver xenotransplantation. Front. Immunol. 13, 827535 (2022).
Navarro-Alvarez, N. et al. The effects of exogenous administration of human coagulation factors following pig-to-baboon liver xenotransplantation. Am. J. Transplant. 16, 1715–1725 (2016).
Yeh, H. et al. Increased transfusion-free survival following auxiliary pig liver xenotransplantation. Xenotransplantation 21, 454–464 (2014).
Kim, K. et al. Up to 9-day survival and control of thrombocytopenia following alpha1,3-galactosyl transferase knockout swine liver xenotransplantation in baboons. Xenotransplantation 19, 256–264 (2012).
Ekser, B. et al. Impact of thrombocytopenia on survival of baboons with genetically modified pig liver transplants: clinical relevance. Am. J. Transplant. 10, 273–285 (2010).
Tao, K.-S. et al. Gene-modified pig-to-human liver xenotransplantation. Nature 641, 1029–1036 (2025).
Montgomery, R. A., Griesemer, A. D., Segev, D. L. & Sommer, P. The decedent model: a new paradigm for de-risking high stakes clinical trials like xenotransplantation. Am. J. Transplant. 24, 526–532 (2024).
McRae, M. P., Helmke, S. M., Burton, J. R. Jr. & Everson, G. T. Compartmental model describing the physiological basis for the HepQuant SHUNT test. Transl. Res. 252, 53–63 (2023).
Hillmen, P. et al. Pegcetacoplan versus eculizumab in paroxysmal nocturnal hemoglobinuria. N. Engl. J. Med. 384, 1028–1037 (2021).
Connolly, M. R. et al. Humanized von Willebrand factor reduces platelet sequestration in ex vivo and in vivo xenotransplant models. Xenotransplantation 28, e12712 (2021).
Scully, M., Howells, L. & Lester, W. A. Impact of new medications on the treatment of immune TTP. Blood 145, 1353–1357 (2025).
Lee, K. W. et al. Auxiliary liver xenotransplantation technique in a transgenic pig-to-non-human primate model: a surgical approach to prolong survival. Xenotransplantation 30, e12814 (2023).
Shirini, K. & Meier, R. P. H. Systematic review and comparative outcomes analysis of NHP liver allotransplants and xenotransplants. Xenotransplantation 32, e70017 (2025).
Calne, R. Y. et al. Hepatic allografts and xenografts in primates. Lancet 1, 103–106 (1970).
Ramirez, P. et al. Life-supporting human complement regulator decay accelerating factor transgenic pig liver xenograft maintains the metabolic function and coagulation in the nonhuman primate for up to 8 days. Transplantation 70, 989–998 (2000).
Ramirez, P. et al. Prevention of hyperacute rejection in a model of orthotopic liver xenotransplantation from pig to baboon using polytransgenic pig livers (CD55, CD59, and H-transferase). Transplant. Proc. 37, 4103–4106 (2005).
Zhang, Z. et al. Cytokine profiles in Tibetan macaques following alpha-1,3-galactosyltransferase-knockout pig liver xenotransplantation. Xenotransplantation 24, e12321 (2017).
LaMattina, J. C. et al. Pig-to-baboon liver xenoperfusion utilizing GalTKO.hCD46 pigs and glycoprotein Ib blockade. Xenotransplantation 21, 274–286 (2014).
Hara, H., Gridelli, B., Lin, Y. J., Marcos, A. & Cooper, D. K. Liver xenografts for the treatment of acute liver failure: clinical and experimental experience and remaining immunologic barriers. Liver Transpl. 14, 425–434 (2008).
Starzl, T. E., Marchioro, T. L., Faris, T. D., McCardle, R. J. & Iwaski, Y. Avenues of future research in homotransplantation of the liver with particular reference to hepatic supportive procedures, antilymphocyte serum, and tissue typing. Am. J. Surg. 112, 391–400 (1966).
Czigany, Z. et al. Bridging therapies-ex vivo liver xenoperfusion and the role of machine perfusion: an update. Xenotransplantation 32, e70011 (2025).
Pascher, A., Sauer, I. M., Hammer, C., Gerlach, J. C. & Neuhaus, P. Extracorporeal liver perfusion as hepatic assist in acute liver failure: a review of world experience. Xenotransplantation 9, 309–324 (2002).
Nasralla, D. et al. A randomized trial of normothermic preservation in liver transplantation. Nature 557, 50–56 (2018).
Dahm, F., Georgiev, P. & Clavien, P. A. Small-for-size syndrome after partial liver transplantation: definition, mechanisms of disease and clinical implications. Am. J. Transplant. 5, 2605–2610 (2005).
Fernandes, M. R. et al. Small-for-size syndrome: systemic review in a porcine experimental model. Transplant. Proc. 54, 1352–1356 (2022).
Du, X., Chang, Y. & Song, J. Use of brain death recipients in xenotransplantation: a double-edged sword. Xenotransplantation 32, e70010 (2025).
Kolev, M., Barbour, T., Baver, S., Francois, C. & Deschatelets, P. With complements: C3 inhibition in the clinic. Immunol. Rev. 313, 358–375 (2023).
Musto, J. et al. Recovery and outcomes of patients denied early liver transplantation for severe alcohol-associated hepatitis. Hepatology 75, 104–114 (2022).
Fosbury, E., Drebes, A., Riddell, A. & Chowdary, P. Review of recombinant anti-haemophilic porcine sequence factor VIII in adults with acquired haemophilia A. Ther. Adv. Hematol. 8, 263–272 (2017).
Chihara, R. K. et al. Primary porcine Kupffer cell phagocytosis of human platelets involves the CD18 receptor. Transplantation 92, 739–744 (2011).
Paris, L. L., Chihara, R. K., Sidner, R. A., Tector, A. J. & Burlak, C. Differences in human and porcine platelet oligosaccharides may influence phagocytosis by liver sinusoidal cells in vitro. Xenotransplantation 19, 31–39 (2012).
Peng, Q. et al. Mechanisms of xenogeneic baboon platelet aggregation and phagocytosis by porcine liver sinusoidal endothelial cells. PLoS ONE 7, e47273 (2012).
Schulte Am Esch, J. et al. O-linked glycosylation and functional incompatibility of porcine von Willebrand factor for human platelet GPIb receptors. Xenotransplantation 12, 30–37 (2005).
