1013 CD163 IS A MECHANISTIC BIOMARKER IN ACUTE LIVER FAILURE REFLECTING A MACROPHAGE ACTIVATION LIKE SYNDROME

POSTERS In contrast, necessity of RRT was associated with significantly higher mortality rates in patients not listed for transplantation (71% vs. 13%, p < 0.05). Multivariate regression revealed SAPSII score as the best independent predictor of 28d-mortality in these patients (HR = 1.055; 95% CI=1.029; 1.083; P < 0.001). SAPSII score >41 predicted 28d-mortality with a specificity of 99%, and sensitivity of 89.5% (AUROC = 0.924). Conclusion: High SAPSII score and HE 3–4 on ICU admission were independent predictors for RRT in ALF. Although mortality in patients with AKI not eligible for LT was high, RRT should not be withheld in these patients a priori. SAPSII score on admission, but not AKI requiring RRT, was the best independent predictor of mortality in patients not eligible for LT. 1012 SERUM CREATININE AND THE PRESENCE OF ENCEPHALOPATHY AT PRESENTATION MAY PREDICT MORTALITY IN CHILDREN WITH ACUTE LIVER FAILURE A. Stefanescu1 , T. Pop1 , H. Stefanescu2,3 , D. Feier2,3 , A. Bizo1 , N. Miu1 . 1 2nd Pediatric Clinic, 2 3rd Medical Clinic, Iuliu Hatieganu University of Medicine and Pharmacy, 3 Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania E-mail: [email protected] Background and Aims: Acute liver failure (ALF) requires fast and efficient management, based on accurate prognosis factors. Our aim was to identify common clinical and biological parameters of prognostic value in a pediatric population with ALF. Methods: We performed a cross-sectional study on 38 consecutive patients diagnosed with ALF in the 2nd Pediatrics Clinic, ClujNapoca, Romania, between January 2008 and October 2012. The inclusion criteria were: age between 0 and 18 years, no previous cause of encephalopathy, acute hepatic decompensation (including acute-on-chronic liver failure). Commonly available serum biomarkers at presentation were recorded: liver function tests (transaminases, total protein and albumin, coagulation parameters), glycemia, creatinin, sodium, potassium. We also assessed the degree of hepatic encephalopathy and calculated the PELD score in each patient. Overall survival at 45 days was assessed. Non-parametric statistic tests were used for data analysis. Results: We included 38 children with a mean age of 7.43 years, 50% males. The most frequent etiology was mushroom poisoning (73.7%); the other etiologies were acute viral hepatitis (8.7%), drug intoxication (8.7%) and acute-on-chronic liver disease – Wilson’s disease or biliary atresia (8.7%). Fifty percent of the patients died within the follow-up period. In univariate analysis, the following factors were found to positively or negatively correlate with shortterm mortality: total bilirubin, transaminases, total protein and albumin, prothrombin time, INR, creatinin, sodium, PELD score and the presence of encephalopathy (p < 0.05 in all cases). In multivariate analysis, however, only hepatic encephalopathy and serum creatinin were found to independently predict mortality (R2 =0.78, p < 0.001). Conclusion: In our data set, high creatinin level and the presence of encephalopathy seemed to predict mortality in children with ALF. Interestingly, PELD score was not found to independently predict death, maybe because of the heterogeneity of the sets in terms of etiology and age. However, both creatinin and encephalopathy are linked with the severity of liver disease in adults, so the correlation is not circumstantial. Creatinin measurement and encephalopathy assessment are easy to perform in ER, and should always be performed in children with ALF.

1013 CD163 IS A MECHANISTIC BIOMARKER IN ACUTE LIVER FAILURE REFLECTING A MACROPHAGE ACTIVATION LIKE SYNDROME C. Antoniades1,2 , E. Triantafyllou2 , R. Gadhok1 , R. Abeles2 , A. Quaglia2 , W. Khamri1 , R. Tidswell1 , M. McPhail1 , L. Possamai1 , W. Bernal2 , M. Heneghan2 , Y. Ma2 , G. Auzinger2 , N. Heaton2 , M. Thursz1 , J. Wendon2 . 1 Section of Hepatology, Imperial College London, 2 Intitute of Liver Sciences, King’s College London, London, UK E-mail: [email protected] Introduction: CD163 is highly specific marker of macrophage (mf) activation and a biomarker of disease severity in mf-driven diseases such as haemophagocytic syndromes. Mf activation is a key determinant of systemic inflammatory responses and clinical outcome in acute liver failure (ALF). We sought to examine the prognostic utility, source and temporal evolution of CD163 expression in ALF. Methods: In ALF patients, soluble CD163 (sCD163), MCP-1, TNF-a, IL-6 and IL-10 (all pg/ml) were determined on admission (n = 76; acetaminophen-induced ALF [n = 56; AALF]; non-acetaminopheninduced ALF [n = 20; NAALF]) and sequentially (n = 20), 15 patients with chronic liver disease (CLD) and 22 healthy volunteers (HC). Monocyte (CD14+) CD163 expression was determined in 37 AALF and 15 HC using flow cytometry. Regional levels (hepatic vein [HV], portal vein [PV]) of sCD163 were determined in 3 ALF patients at the time of transplantation. Immunohistochemistry was used to determine the mf (CD68+) infiltrate in 10 ALF (5 AALF/5 seronegative) explants. Using laser capture microdissection (LCM), CD163 concentration was determined in necrotic and non-necrotic areas of 3 AALF explants AALF explants and 3 control liver tissue using LC-SRM proteome analysis. Results: AALF (1925 pg/ml), NAALF (2233 pg/ml), CLD (1408 pg/ml) patients had significantly higher sCD163 levels compared to HC (500 pg/ml; all p < 0.01). NAALF patients had significantly higher levels compared to AALF patients (p = 0.02). AALF patients with an adverse outcome (OLT/death) had significantly higher sCD163 levels compared to those who survived on supportive medical care (2180vs1430; p < 0.001). sCD163 reduced following transplantation (2260vs1067 pg/ml; p < 0.01) in AALF patients. Admission sCD163 levels strongly correlated with outcome (AUROC=0.83 [0.69– 0.96; p = 0.0002]), INR (r = 0.6; p < 0.01), lactate (r = 0.6, p < 0.01), pH (r = −0.52; p < 0.01), encephalopathy (r = 0.63; p < 0.01), IL-6 (r = 0.7; p < 0.01), IL-10 (r = 0.47; p = 0.02), MCP-1 (r = 0.5; p < 0.01) and TNF-a (r = 0.46; p = 0.03). % CD14+CD16-CD163+ expression was significantly reduced in AALF compared to HC (62.55% vs 91%; p < 0.001). Analysis of ALF explants reveals a dense mf (CD68+) infiltrate and elevated intrahepatic and regional (HV>PV) concentrations CD163. Conclusion: Our data indicate that sCD163 is released from activated hepatic mf and circulating monocytes in ALF and strongly correlate with disease severity and outcome. Further studies are required to examine whether ALF represents a spectrum of macrophage activation syndrome. 1014 Withdrawn

Journal of Hepatology 2013 vol. 58 | S409–S566

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