A non-human primate model of acute liver failure suitable for testing liver support systems

Ranjeet S. Kalsi, Alina Ostrowska, Adam Olson, Mubina Quader, Melvin Deutsch, Norma J. Arbujas-Silva, Jen Symmonds, Alejandro Soto-Gutierrez, John J. Crowley, Miguel Reyes-Mugica, Giselle Sanchez-Guerrero, Hartmut Jaeschke, Bruce P. Amiot, Marilia Cascalho, Scott L. Nyberg, Jeffrey L. Platt, Edgar N. Tafaleng, Ira J. Fox

Research output: Contribution to journalArticlepeer-review


Acute hepatic failure is associated with high morbidity and mortality for which the only definitive therapy is liver transplantation. Some fraction of those who undergo emergency transplantation have been shown to recover native liver function when transplanted with an auxiliary hepatic graft that leaves part of the native liver intact. Thus, transplantation could have been averted with the development and use of some form of hepatic support. The costs of developing and testing liver support systems could be dramatically reduced by the availability of a reliable large animal model of hepatic failure with a large therapeutic window that allows the assessment of efficacy and timing of intervention. Non-lethal forms of hepatic injury were examined in combination with liver-directed radiation in non-human primates (NHPs) to develop a model of acute hepatic failure that mimics the human condition. Porcine hepatocyte transplantation was then tested as a potential therapy for acute hepatic failure. After liver-directed radiation therapy, delivery of a non-lethal hepatic ischemia-reperfusion injury reliably and rapidly generated liver failure providing conditions that can enable pre-clinical testing of liver support or replacement therapies. Unfortunately, in preliminary studies, low hepatocyte engraftment and over-immune suppression interfered with the ability to assess the efficacy of transplanted porcine hepatocytes in the model. A model of acute liver failure in NHPs was created that recapitulates the pathophysiology and pathology of the clinical condition, does so with reasonably predictable kinetics, and results in 100% mortality. The model allowed preliminary testing of xenogeneic hepatocyte transplantation as a potential therapy.

Original languageEnglish (US)
Article number964448
JournalFrontiers in Medicine
StatePublished - Sep 30 2022


  • acute liver failure (ALF)
  • hepatic ischemia-reperfusion injury
  • liver-directed radiation therapy
  • non-human primates (NHPs)
  • xenogeneic hepatocyte transplantation

ASJC Scopus subject areas

  • Medicine(all)


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