POSTERS P339 PON1 DIRECTED RECALIBRATION OF MACROPHAGE LIPID HOMEOSTASIS LEADS TO REVERSAL OF CIRCULATING FOAMY PHENOTYPE AND PREDICTS OUTCOME IN ACUTE ON CHRONIC LIVER FAILURE (ACLF) PATIENTS J.S. Maras 1 , S. Das 2 , S.S. Jaswal 2 , R. Mahiwal 3 , C. Kumar 3 , D. Kumar 2 , H.H.C. Gawda 4 , A. Rastogi 5 , N.T. Pati 2 , S. Sharma 2 , A. Pandey 4,6 , S.K. Sarin 3 . 1 Institute of Liver & Biliary Sciences, 2 Department of Research, 3 Hepatology, Institute of Liver & Biliary Sciences, New Delhi, 4 Institute of Bioinformatics, Bangalore, 5 Department of Pathology, Institute of Liver & Biliary Sciences, New Delhi, India; 6 Departments of Biological Chemistry, Pathology, Oncology, and Surgery, McKusick-Nathans Institute of Genetic Medicine, Institute of Basic Biomedical Sciences, Section of Hepatology and Liver Transplantation, Johns Hopkins University School of Medicine, Baltimore, MD, United States E-mail: jassi2param@gmail.com Background and Aims: Acute on chronic liver failure is a rapidly progressive severe illness with a potential of reversibility. Lipid metabolism and transport is dysregulated in ACLF and foamy degeneration in severe alcoholics is correlated with mortality. Whether circulating proteins in ACLF potentiate alteration in macrophage lipid-homeostasis, phenotype or functional characteristics is not known. Aim: To determine the mechanism involved in dysregulation of lipid-homeostasis in macrophages in patients with ACLF due to alcohol. Methods: Quantitative protein expression profiling was validated using ELISA, on ACLF (n = 40), compensated cirrhosis (n = 20) and healthy-controls (n = 20). Combinatorial recombinant protein treatment [CRPT] on rat-BMDM/THP1 cells with conditional media (ACLF/CLD/HC-plasma) was assessed for lipid-homeostasis by qPCR/immuno-fluorescence/histochemistry for phenotypic/ functional characterization. Results: 120 proteins (>2 folds) were identified. ELISA-validation documented significant reduction of proteins involved in lipid- homeostasis (Pon1, ApoB, ApoA1, ApoA2, ApoC1, ApoC3 and ApoD) in ACLF [p≤0.05]. Significantly reduced levels of Pon1, ApoB and concomitant increase of ox-LDL was correlated with ACLF-non- survivors. BMDM/THP1 on ACLF condition-media documented increased nile-red-staining and altered expression of CD36, SRB1, FAS, SREBP1, TNF-alpha, IL-6, ABCA1,G1, LDLR, LXR b , EPO as compared to CLD and HC condition-media [>2 folds]. CRPT of [PON1, HDL, and ApoA1] on BMDM/THP1 reversed nile red staining and gene expression profile of macrophages. Circulating Pon1 (<12.3 ng/ml) correlated with severity (p < 0.05) and 28-day survival (p < 0.027, HR 0.12 [0.021–0.712]) in ACLF. Conclusions: Low Pon1 level results in an altered lipid- homeostasis in ACLF macrophages. Exogenous PON1 treatment recalibrates macrophage lipid-homeostasis, decreases foamy phenotype. Resubstituion or augmentation of Pon1 may have prognostics/therapeutic implications in alcohol associated ACLF. P340 ALBUMIN EXCHANGE AND ENDOTOXIN REMOVAL USING THE NOVEL UCL-LIVER DIALYSIS DEVICE (UCL-LDD) PROLONGS SURVIVAL IN ACETAMINOPHEN-INDUCED ACUTE LIVER FAILURE (ALF) K.C.L. Lee 1 , L. Baker 1 , G. Stanzani 1 , H. Alibhai 1 , Y.M. Chang 1 , P. Leckie 2 , C. Palacios Jimenez 1 , P. Giordano 1 , B. Agarwal 3 , R. Mookerjee 2 , R. Jalan 2 , N. Davies 2 . 1 Royal Veterinary College, Hertfordshire, 2 Liver Failure Group, University College London (UCL), Institute of Liver and Digestive Health, 3 Royal Free London NHS Foundation Trust, London, United Kingdom E-mail: klee@rvc.ac.uk Background and Aims: In liver failure endotoxaemia contributes to infection risk and albumin function is irreversibly destroyed. UCL- LDD is a novel extracorporeal support device incorporating a high cut-off filter for albumin exchange and an endotoxin adsorption filter. We aimed to test whether UCL-LDD treatment improved survival in a pig model of acetaminophen-induced acute liver failure (PALF). Methods: Pigs were randomised to 3 groups: PALF+UCL-LDD (n = 9); PALF+renal replacement therapy (RRT) (n = 7); and PALF- control+RRT (n = 4). UCL-LDD or RRT was started 2h after onset of ALF, defined by INR ≥ 3. Thereafter, pigs were supported until death or terminated at 20h. Human albumin infusion was started at 1.6g/h. Survival, clinical progression, endotoxaemia and redox state of human albumin were assessed. Results: UCL-LDD resulted in 75% reduced risk of death compared to RRT (hazard ratio=0.253, p = 0.0233). All PALF+RRT pigs died: median survival 12.2h (range: 10–15h). Three PALF+UCL-LDD pigs survived: median survival 16h (range: 9–20h). Figure: UCL-LDD improves survival in PALF. During first 6h of treatment, UCL-LDD resulted in a more stable cardiovascular status with delayed development of high cardiac output failure (lower fluid volume requirement, p = 0.018; cardiac index, p = 0.023; stroke volume, p = 0.044; and right ventricular stroke work, p = 0.003) and ventilator profile (lower inspiratory pressures, p = 0.028 and respiratory rate, p < 0.001). Increase in endotoxaemia was lower with UCL-LDD (31±0.2%) than with RRT (77±0.1%), p = 0.042 and percentage irreversibly oxidised human non-mercaptalbumin-2 was lower with UCL-LDD (11±1%) than with CD (15±1%), p = 0.043. Conclusions: Treatment of ALF pigs with UCL-LDD prolonged survival of ALF pigs by impacting on albumin function and endotoxaemia. A clinical trial of UCL-LDD is justified. P341 NON-INVASIVE IMAGING OF KUPFFER CELL STATUS USING RADIOLABELLED MANNOSYLATED ALBUMIN V. Mahajan 1 , S. Hartimath 1 , R. Comley 2 , M. Stefan-Gueldner 2 , A. Roth 2 , K. Poelstra 3 , C. Reker-Smit 3 , J. Kamps 1 , R. Dierckx 1 , E. de Vries 1 . 1 University Medical Center Groningen, Groningen, Netherlands; 2 Hoffman La Roche, Basel, Switzerland; 3 University of Groningen/RUG, Groningen, Netherlands E-mail: v.mahajan@umcg.nl Background and Aims: Kupffer cells are responsible for maintaining liver homeostasis and have a vital role in chronic hepatotoxicity and various liver diseases. Positron Imaging Tomography (PET) is a non-invasive imaging technique that S180 Journal of Hepatology 2014 vol. 60 | S67–S214