Extracorporeal liver assist device to exchange albumin and remove endotoxin in acute liver failure: Results of a pivotal pre-clinical study

Karla C L Lee, Luisa A Baker, Giacomo Stanzani, Hatim Alibhai, Yu Mei Chang, Carolina Jimenez Palacios, Pamela J Leckie, Paola Giordano, Simon L Priestnall, Daniel J Antoine, Rosalind E Jenkins, Christopher E Goldring, B Kevin Park, Fausto Andreola, Banwari Agarwal, Rajeshwar P Mookerjee, Nathan A Davies, Rajiv Jalan

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

BACKGROUND & AIMS: In acute liver failure, severity of liver injury and clinical progression of disease are in part consequent upon activation of the innate immune system. Endotoxaemia contributes to innate immune system activation and the detoxifying function of albumin, critical to recovery from liver injury, is irreversibly destroyed in acute liver failure. University College London-Liver Dialysis Device is a novel artificial extracorporeal liver assist device, which is used with albumin infusion, to achieve removal and replacement of dysfunctional albumin and reduction in endotoxaemia. We aimed to test the effect of this device on survival in a pig model of acetaminophen-induced acute liver failure.

METHODS: Pigs were randomised to three groups: Acetaminophen plus University College London-Liver Dialysis Device (n=9); Acetaminophen plus Control Device (n=7); and Control plus Control Device (n=4). Device treatment was initiated two h after onset of irreversible acute liver failure.

RESULTS: The Liver Dialysis Device resulted in 67% reduced risk of death in acetaminophen-induced acute liver failure compared to Control Device (hazard ratio=0.33, p=0.0439). This was associated with 27% decrease in circulating irreversibly oxidised human non-mercaptalbumin-2 throughout treatment (p=0.046); 54% reduction in overall severity of endotoxaemia (p=0.024); delay in development of vasoplegia and acute lung injury; and delay in systemic activation of the TLR4 signalling pathway. Liver Dialysis Device-associated adverse clinical effects were not seen.

CONCLUSIONS: The survival benefit and lack of adverse effects would support clinical trials of University College London-Liver Dialysis Device in acute liver failure patients.

Original languageEnglish
Pages (from-to)634-42
Number of pages9
JournalJournal of Hepatology
Issue number3
Publication statusPublished - Sept 2015

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Endotoxins
  • Extracorporeal Circulation
  • Female
  • HMGB1 Protein
  • Liver Failure, Acute
  • Liver, Artificial
  • Serum Albumin
  • Signal Transduction
  • Sorption Detoxification
  • Swine
  • Toll-Like Receptor 4
  • Journal Article
  • Research Support, Non-U.S. Gov't


Dive into the research topics of 'Extracorporeal liver assist device to exchange albumin and remove endotoxin in acute liver failure: Results of a pivotal pre-clinical study'. Together they form a unique fingerprint.

Cite this