OC-023 Extracorporeal liver support using UCL-arsenel reduces inflammation, improves haemodynamic function and increase survival time in a porcine paracetamol-induced acute liver failure model. (28th May 2012)

• Record Type: Journal Article
• Authors: Leckie, P; Proven, A; Thiel, C; Thiel, K; Schenk, M; Flieg, R; Storr, M; Jalan, R; Davies, N
• Is Part Of: Gut. Volume 61(2012)Supplement 2
• Page Start: A10
• Page End: A10
• Publication Date: 2012-05-28
• Subjects: Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2012-302514a.23
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Introduction: Though the incidence of liver disease continues to increase, an effective liver support device remains an unmet clinical need. We have demonstrated that in liver failure, albumin function is irreversibly damaged, preventing detoxification processes, and that bacterial endotoxins induce systemic inflammation and neutrophil dysfunction. To date, toxin removal devices have failed to demonstrate clinical efficacy, which may be due to an inability to address albumin damage and/or inflammation. An albumin replacement system with a novel endotoxin ligation (ARSeNEL) component was developed to selectively to adsorb endotoxin and replace damaged albumin in patients' plasma. Methods: We tested the device in an acetominophen model of acute liver failure (ALF). 16 female landrace pigs (eight ALF, five ALF + UCL-ARSeNEL) were studied. Irreversible ALF was induced by acetaminophen administration via a jejunel catheter, confirmed by deranged clotting function (PT >30% normal). Treatment was with UCL-ARSeNEL or CVVH control within 2 h of ALF confirmation. The ARSeNEL device consists of three components; plasmapheresis, endotoxin and high cut-off (100 kDa) filters; with fresh frozen plasma replacing ultrafiltered plasma. Endpoints were: survival; ICP; heamodynamic parameters, standard biochemistry; cytokines; albumin damage; and plasma endotoxin levels. Results: UCL-ARSeNEL significantly increased survival post ALF (ALF 15.8±2.4 h vs UCL-ARSeNEL 23.8±1.9 h; p=0.02). Endotoxin reduced by a quarter (1.99±0.18 Eu/ml vs 1.42±0.21 Eu/ml) in the device group at 16 h. The changes in ICP index (1.7±0.07 vs 1.4±1.58), INR (16.6±6.6 vs 6.8±0.5), ischaemia-modified albumin ratio (0.45±0.166 vs 0.35±0.108), noradrenaline requirement (61.11±15.4 vs 28.7±15.2 μg/Kg), and mean arterial pressure (71±7.6 vs 87±6.0 mm Hg) showed marked improvement in the UCL-ARSeNEL group. Measured inflammatory cytokines IL8, IL6, IL1b, TNFa and neutrophil activation (spontaneous burst p=0.03) were all found to be reduced in the ARSeNEL treated group compared with ALF control. Conclusion: These results confirm that UCL-ARSeNEL improves survival in ALF by addressing key pathophysiological derangements such as albumin dysfunction and endotoxinaemia; which impact upon systemic inflammation and end-organ function. The reduction in inflammation is associated with improved vascular function and reduced inotropic support requirements. Competing interests: None declared.