592 CARDIAC CIRRHOSIS CONTRIBUTES TO THE WATER RETENTION IN PATIENTS WITH HEART FAILURE

POSTERS 591 BACTERIAL DNA MEASUREMENTS IN PATIENTS WITH CIRRHOSIS UNDERGOING TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT (TIPS) INSERTION C. Mortensen1,2,3 , S. Karlsen4 , H. Grønbæk4 , D.T. Nielsen5 , S. Frevert6 , O. Clemmesen7 , S. Møller2,3 , J.S. Jensen8 , F. Bendtsen1,3 . 1 Department of Gastroenterology, 2 Centre of Functional Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, Hvidovre University Hospital, 3 Faculty of Health Sciences, University of Copenhagen, Copenhagen, 4 Department of Medicine V, 5 Department of Radiology, Aarhus University Hospital, Aarhus, 6 Department of Radiology, 7 Department of Hepatology, Rigshospitalet, 8 Mycoplasma Laboratory, Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark E-mail: [email protected] Background and Aims: Bacterial translocation may be associated with abnormal immune activation leading to haemodynamic alterations and a poor outcome in patients with cirrhosis. Presence of bacteria in lymph nodes, bacterial products, and bacterial DNA (bDNA) have been proposed as markers of bacterial translocation. In this study, we investigated bDNA and its relation to markers of inflammation in the portal and hepatic venous circulations in patients with cirrhosis undergoing TIPS insertion. Methods: In 28 cirrhotic patients undergoing TIPS insertion, we analysed blood samples for bDNA and markers of inflammation. The majority of patients had advanced cirrhosis (Child–Pugh Class (A/B/C): 1/14/13), most often caused by alcohol (n = 20). The main indications for TIPS insertion were refractory ascites (19 patients) and recurrent variceal bleeding (9 patients). Presence of bDNA was assessed by quantitative broad-range PCR. Soluble urokinasetype plasminogen activator receptor (SUPAR), tumor necrosis factoralpha, lipopolysaccharide-binding protein and C-reactive protein were measured by ELISA, and interleukin 6, interleukin 8, vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha were analysed by luminex multiplex technology. Results: bDNA-levels were similar in the hepatic and portal vein (median 6.07 (3.06–10.61) versus 6.51 gene copies (3.15–11.52), p = 0.80). bDNA levels in hepatic and portal veins correlated significantly (r = 0.62, p = 0.002). In patients receiving antibiotics, bDNA tended to be lower, reaching significance in the hepatic vein (p = 0.025). Dividing patients into groups according to bDNA, we found no significant difference with respect to markers of inflammation. Markers of inflammation in general did not differ between the hepatic and portal veins. However, SUPAR and VEGF were higher in the hepatic vein (p = 0.031, and 0.003, respectively). Conclusions: Bacterial DNA was measurable in the hepatic and portal vein blood and the levels correlated significantly but without a significant transhepatic gradient. bDNA tended to be lower in patients treated by antibiotics compared to untreated patients. The absence of a transhepatic gradient suggests that in patients with advanced liver disease, no major hepatic elimination of bDNA occurs. In contrast previous reports, bDNA was not related to markers of inflammation. 592 CARDIAC CIRRHOSIS CONTRIBUTES TO THE WATER RETENTION IN PATIENTS WITH HEART FAILURE C. Dietrich1 , E. Yagmur2 , H.K. Seitz1 , C. Viedt-Suelmann1 , S. Mueller1 . 1 Department of Internal Medicine, Salem Medical Center and Center for Alcohol Research, University of Heidelberg, Heidelberg, 2 Institute for Laboratory Medicine Aachen, Aachen, Germany E-mail: [email protected] Objectives: Liver cirrhosis in heart failure patients is considered a bystander and water accumulation is thought to mainly originate from forward failure, arterial underfilling with activation of the renin angiotensin system (RAAS). We here assess cardiac fibrosis S242

in patients with heart failure by sequential assessment of liver stiffness (LS) and analyse the cardiac and hepatic determinants of water retention. Methods and Patients: 100 patients with acute decompensated heart failure were retrospectively analysed. In an additional prospective validation cohort, various serum hormones of water status, liver tests, echocardiography and LS were sequentially measured in 39 patients with acute heart failure at the days of admission and release. Results: 44% of patients in the prospective cohort showed morphological signs of liver cirrhosis. In confirmation, LS exceeded 8 kPa in ca. 70% of the retro- and prospective cohort (66.6% vs 70.8%). LS was the best predictor of liver cirrhosis (AUROC 0.998) although it decreased during diuretic therapy in 88% with a mean of 5.38 kPa. Weight loss correlated best with the decrease of LS (r = 0.759, p < 0.0001), signs of cirrhosis or right heart failure (e.g. TDI’s) but not forward failure (ejection fraction). Likewise, presence of cirrhosis correlated significantly with LS (r = 0.844, p < 10−6 ), size of right ventricule and atrium (r = 0.796, p < 2x10−6 and r = 0.635, p < 0.005) and GGT (r = 0.622, p < 0.005) but no forward failure. Major discriminating factors between cirrhotic and non-cirrhotics were LS, right atrium size, presence of ascites and GGT. Hormones of water regulation such as copeptin and aldosterone were all higher in cirrhotics (28.7 vs. 11.6 pmol/l and 103.4 vs. 24.0 pmol/l) despite the intake of aldosterone antagonists. Interestingly, water retention and LS were significantly correlated with the C1q/TNF related protein (CTRP)-1 (r = 0.692, p < 0.005 and r = −0.603, p < 0.01) a novel and important upstream regulator of aldosterone. Conclusion: Cardiac cirrhosis/congestion seems to be a major factor for the water accumulation in patients with heart failure leading to further increase of the RAAS. Our data provide novel mechanistic rationale for the treatment of patients with heart failure with aldosterone antagonists and the effective surveillance via LS measurements. 593 LENALIDOMIDE AMELIORATES THE PORTAL HYPERTENSIVE SYNDROME IN NON-CIRRHOTIC AND CIRRHOTIC PORTAL HYPERTENSIVE ANIMALS B. Payer1 , T. Reiberger1 , P. Schwabl1 , T. Horvatits1 , V. Fuhrmann1 , B. Angermayr2 , M. Peck-Radosavljevic1 , Hepatic Experimental Hemodynamic Laboratory of Vienna. 1 Gastroenterology & Hepatology, Medical University Vienna, Vienna, 2 LHK St.P¨ olten, 2. Med. Abteilung, St. P¨ olten, Austria E-mail: [email protected] Introduction: We aimed to investigate the influence of lenalidomide, a immunomodulatory and anti-angiogenic derivative of thalidomide, on portal hemodynamics, angiogenesis and inflammation in cirrhotic and non-cirrhotic portal hypertensive rats. Methods: Male Sprague Dawley rats underwent either partial portal vein ligation (PPVL; isolated portal hypertension), bile duct ligation (BDL; cirrhotic portal hypertension), or sham-operation (SO). Treatment with lenalidomide (250 mg/kg) or vehicle (VEH) was given via gavage for seven days prior to hemodynamic measurements. In PPVL hemodynamic studies were performed after seven days, in BDL 28 days after surgery measuring portal pressure (PP), mean arterial pressure (MAP), and portosystemic collateral blood flow (PSCBF). Splanchnic and hepatic tissues were analyzed for mRNA (RT-PCR) and protein expression (western blot) of angiogenic and inflammatory markers. Results: In PPVL portal pressure was significantly reduced by LENA treatment (15.2±0.9 vs. 12.7±0.5 vs. mmHg; p = 0.02), while in BDL animals no significant effect of lenalidomide on portal pressure (13.9±2 vs. 12.4±2 mmHg; p = 0.128) was observed. Comparing VEH- to LENA-treated animals, PSCBF was significantly decreased both in the PPVL (86±7% vs. 27±7%; p < 0.001) and in the BDL

Journal of Hepatology 2013 vol. 58 | S229–S407