1. Extracorporeal liver assist device to exchange albumin and remove endotoxin in acute liver failure: Results of a pivotal pre-clinical study
- Author
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Giacomo Stanzani, Rajiv Jalan, P Leckie, Rosalind E. Jenkins, Daniel J. Antoine, H I K Alibhai, Luisa A. Baker, Christopher E. Goldring, Paola Giordano, Banwari Agarwal, Fausto Andreola, Carolina Palacios, Karla C. L. Lee, Nathan Davies, B. Kevin Park, Simon L. Priestnall, Yu-Mei Chang, and Rajeshwar P. Mookerjee
- Subjects
HNA-2, irreversibly oxidised human non-mercaptalbumin-2 ,SIRS, systemic inflammatory response syndrome ,Extracorporeal Circulation ,ACLF, acute-on chronic liver failure ,Swine ,medicine.medical_treatment ,DAMP, damage-associated molecular pattern ,Control-CD, group treated with placebo, water and CD ,RR, respiratory rate ,IL-1ra, IL-1 receptor antagonist ,INR, international normalised ratio ,UCL-LDD ,Liver transplantation ,SVI, stroke volume index ,Gastroenterology ,TLR4, toll-like receptor 4 ,PaCO2, partial pressure of carbon dioxide in arterial blood ,APAP-UCL-LDD, group treated with APAP and UCL-LDD ,0302 clinical medicine ,DNA, deoxyribonucleic acid ,Endotoxin ,HNA-1, reversibly oxidised human non-mercaptalbumin-1 ,Medicine ,HMGB1 Protein ,Liver injury ,0303 health sciences ,biology ,HR, heart rate ,Liver dialysis ,Pinsp, inspiratory pressures ,ELISA, enzyme-linked immunosorbent assay ,MAP, mean arterial pressure ,PaO2/FiO2, ratio of partial pressure of oxygen in arterial blood to percentage of oxygen in inspired gases ,3. Good health ,PCWP, pulmonary capillary wedge pressure ,UCL-LDD, University College London-Liver Dialysis Device ,ICP, intracranial pressure ,030211 gastroenterology & hepatology ,Female ,APAP-CD, group treated with APAP and CD ,LVSWI, left ventricular stroke work index ,medicine.drug ,Research Article ,Signal Transduction ,medicine.medical_specialty ,SVRI, systemic vascular resistance index ,HMGB1, high-mobility group box-1 protein ,Serum albumin ,APAP, acetaminophen ,PALF, porcine model of acute liver failure ,Lung injury ,LT, liver transplantation ,03 medical and health sciences ,ALF, acute liver failure ,Internal medicine ,Hemofiltration ,CD, Control Device ,Animals ,CI, cardiac index ,Serum Albumin ,030304 developmental biology ,Acetaminophen ,MARS, Molecular Adsorbent Recirculating System ,Nalp3, nacht, leucine-rich repeat and pyrin domain-containing protein 3 ,Hepatology ,ALP, alkaline phosphatase ,business.industry ,HAS, human serum albumin ,AST, aspartate amino transferase ,Albumin ,Extracorporeal circulation ,Liver Failure, Acute ,medicine.disease ,Toll-like receptor 4 ,CVP, central venous pressure ,Liver, Artificial ,Surgery ,IL, interleukin ,HMA, non-oxidised human mercaptalbumin ,Endotoxins ,PEEP, positive end expiratory pressure ,PaO2, partial pressure of oxygen in arterial blood ,biology.protein ,RVSWI, right ventricular stroke work index ,Sorption Detoxification ,Extracorporeal liver assist device ,business ,NAPQI, N-acetyl-p-benzoquinone imine ,Acute liver failure - Abstract
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.
- Published
- 2015