1315 Cholangiocyte proliferation and Osteopontin secretion is induced by Schistosoma mansoni egg antigens and cor- relates with fibrosis and portal hypertension in human and murine schistosomiasis Thiago A. Pereira 1,2 , Wing-Kin Syn 4 , Steve S. Choi 1 , Izabela Voieta 3 , Vivian Resende 3 , Marcia M. Souza 2 , William E. Secor 5 , Paula V. Vidigal 3 , Rafal P. Witek 7 , Zilton A. Andrade 2 , Fausto E. Pereira 6 , José R. Lambertucci 3 , Anna Mae Diehl 1 ; 1 Division of Gas- troenterology, Duke University Medical Center, Durham, NC; 2 Lab- oratório de Patologia Experimental, Centro de Pesquisas Gonçalo Moniz/FIOCRUZ, Salvador, Brazil; 3 Faculdade de Medicina, Uni- versidade Federal de Minas Gerais, Belo Horizonte, Brazil; 4 Liver Regeneration and Repair Research Group, Institute of Hepatology, Foundation for Liver Research, London, United Kingdom; 5 Centers for Disease Control and Prevention, Atlanta, GA; 6 Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitória, Brazil; 7 Life Technologies, Carlsbad, CA Background: Schistosomiasis is a leading cause of portal fibro- sis and portal hypertension worldwide. Osteopontin (OPN) is a profibrogenic protein associated with hepatic stellate cell acti- vation and correlates with fibrosis stage in chronic liver dis- eases. Our aims were to investigate if Schistosoma mansoni egg antigens could induce cholangiocyte proliferation and secretion of OPN, and if OPN levels correlate with fibrosis stage and/or degree of portal hypertension. Methods: Mouse cholangiocyte line 603B and primary human cholangiocytes (from Life Technologies) were incubated with 10ug/mL of Solu- ble egg antigen (SEA) or 0.0001ug/mL LPS (control) for 2,4,6,12 and 24 hours. Cells were harvested and analyzed for OPN mRNA by qRTPCR. OPN protein in conditioned media was measured by ELISA, and cell proliferation assessed by BrdU. Mice were infected with S. mansoni for 6 weeks (early; n=5) or 16 weeks (advanced; n=8). Uninfected, age and strain matched mice were controls (n=8). At the end of treatment, mice were sacrificed; liver OPN and αSMA expression was assessed by qRTPCR and IHC; serum OPN was measured by ELISA; liver fibrosis evaluated by Sirius Red staining and mor- phometry. Livers from patients with schistosomiasis mansoni (early fibrosis n=6; advanced fibrosis n= 58) or healthy adults (donors, n=8) were stained for OPN and αSMA, and serum col- lected for OPN measurements. Splenic vein pressures were studied in a subgroup of patients with advanced fibrosis at the time of splenectomy. This study was approved by the Ethics Committee of UFMG (204-06). Results: SEA stimulated cholan- giocyte proliferation and upregulated cholangiocyte-associated OPN secretion (p<0.001). In both mice and humans, liver and serum OPN levels correlated with fibrosis stage (mice: r=0.848; human r=0.61, p=0.000) and αSMA expression (mice: r=0.772, p=0.005; human: r=0.74, p=0.001). A posi- tive correlation was also observed between the number of OPN+ bile ducts and the level of splenic vein pressure(r=0.79; r2=0.624; p=0.01). Conclusions: S. mansoni egg antigens stimulate cholangiocyte proliferation and OPN secretion. OPN levels in the liver and blood correlate with fibrosis stage and severity of portal hypertension. Disclosures: Rafal P. Witek - Stock Shareholder: Life Technologies Anna Mae Diehl - Consulting: Bristol Myers Squibb, Synergy, GlaxoSmithKline, Norgine; Grant/Research Support: GlaxoSmithKline The following people have nothing to disclose: Thiago A. Pereira, Wing-Kin Syn, Steve S. Choi, Izabela Voieta, Vivian Resende, Marcia M. Souza, William E. Secor, Paula V. Vidigal, Zilton A. Andrade, Fausto E. Pereira, José R. Lambertucci 1316 Splanchnic hypercoagulability in cirrhosis correlates with portal hypertension and is exacerbated by bacter- ial infections Sebastian Raffa 1,3 , Juan Carlos Reverter 2 , Susana Seijo 3,4 , Juan G. Abraldes 3,4 , Dolors Tassies 2 , Annalisa Berzigotti 3,4 , Juan Carlos Garcia-Pagan 3,4 , Jaime Bosch 3,4 ; 1 Liver transplantation unit, Fun- dación Favaloro, Buenos Aires, Argentina; 2 Hemotherapy and Hemostasis Department, Hospital Clinic, Barcelona, Spain; 3 Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, Barcelona, Spain; 4 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain Background and aims: Cirrhosis has been recently shown to be a pro-thrombotic condition. This may be due to a relative unbal- ance between endogenous pro- and anti-coagulants and pro- and anti-fibrinolytic factors. This may explain the high incidence of portal vein thrombosis in cirrhosis. We hypothesized that this would be particularly evident in the hepato-splanchnic vascular bed and that it might be favored by bacterial infections. Patients and methods: Sixty-nine patients (pts) with cirrhosis were prospectively studied at the time of HVPG measurements. Six- teen pts were infected and 53 were not. All pts had simultane- ous measurements in hepatic venous and peripheral blood of: Procoagulant factors (I, II, V, VII, VIII, IX, X, XI, XII), von Wille- brand antigen (vWF-Ag), anticoagulant factors: Antithrombin (AT), protein C and S, Markers of coagulation activation: D- dimer, plasmin-antiplasmin complex (PAP), plasminogen activa- tor inhibitor (PAI), prothrombin fragment F1+2 (F1+2), factor VIIa (F-VIIa), activated Factor XII (F.XIIa) and endogenous throm- bin potential (ETP) with/without thrombomodulin, Microparti- cles, tissue factor and platelet-activating factors: Soluble P-selectin and soluble CD40 ligand (CD40Ls). These measure- ments were also done in portal venous blood in 13 pts under- going TIPS. To compare continuous variables, Mann–Whitney U or Wicoxon tests were used. Correlation between continuous variables was done with Spearman rank test. The level of sta- tistical significance was set at a P < 0.05. Results: Patients had a median age of 54.3 years old, 61% were males and cirrho- sis was due to HCV (45%), alcohol (33%) and others (22%). Markers of coagulation activation (PAI, F-VIIa, F1+2, XIIa), vWF-Ag and Microparticles in non-infected cirrhotic patients were significantly and linearly correlated with HVPG, MELD and Child-Pugh score. Microparticles (31.6 vs. 25.9 nM/Eq, P=0.001) and CD40Ls (144 vs. 115 pg/ml, P= 0.002) were higher in hepatic venous blood than in peripheral blood. Levels of F1+2 (1.7 vs. 1.6 nmol/L; P= 0.03), Microparticles (47 vs. 28.8 nM/Eq; P= 0.03) and ETP with thrombomodulin (272 vs. 258 nM; P= 0.02) were significantly higher in portal venous blood than in peripheral blood. Coagulation activation markers and platelet activation markers (CD40Ls and P selectin) were significantly higher in infected cirrhotics, despite a similar Child- Pugh and HVPG. Conclusions: Markers of coagulation activa- tion, and thus the procoagulant state of cirrhosis, increase in correlation with the degree of liver failure and portal hyperten- sion. This is more evident in the splanchnic territory and is fur- ther exacerbated during bacterial infections. Disclosures: Juan Carlos Garcia-Pagan - Grant/Research Support: GORE Jaime Bosch - Advisory Committees or Review Panels: Intercept pharma; Consult- ing: Chiasma, Gilead Science, Norgine, ONO-USA; Grant/Research Support: Gore The following people have nothing to disclose: Sebastian Raffa, Juan Carlos Reverter, Susana Seijo, Juan G. Abraldes, Dolors Tassies, Annalisa Berzigotti HEPATOLOGY, VOLUME 58, NUMBER 4 (SUPPL) AASLD ABSTRACTS 847A