Eph-ephrin signaling mainly affects cell shape and motility by regulating cytoskeletal organization and cell adhesion and

also influences cell proliferation and cell-fate determination.38 In our research, we found that EphA4 suppressed cell migration and invasion see more but promoted cell adhesion, which was the inverse of the functions of miR-10a in HCC cells. As described above, EMT is a process that plays important roles in both development and oncogenesis. During EMT, epithelial cells acquire a mesenchymal phenotype that is characterized by the loss of intercellular junctions and increased cell migration. A previous study has also indicated that EphA4 participates in the MET process,20 and the morphology of the QGY-7703 cells changed after alteration of miR-10a or EphA4 expression (Supporting Fig. 11). We speculated that miR-10a and EphA4 played roles

in the EMT process in HCC. Usually, the loss of intercellular junctions and the increased cell migration during EMT are evidenced by increasing expression of vimentin and decreasing expression of E-cadherin.19 To test our hypothesis, we examined the expression of the epithelial marker E-cadherin and the mesenchymal markers vimentin and ICAM-1. As expected, down-regulation of miR-10a or up-regulation of EphA4 suppressed the EMT phenotype. In other words, miR-10a can increase, whereas EphA4 can suppress HCC cell migration and invasion by mediating the EMT process. Furthermore, Xiang et al.39 indicated

that tumor cells with an epithelial phenotype have a growth advantage in the tissue environment when compared with CHIR-99021 ic50 those with a mesenchymal 上海皓元医药股份有限公司 phenotype. When miR-10a is up-regulated, the expression level of EphA4 is accordingly down-regulated, and the blockage of the EMT process is relieved. HCC cells with enhanced miR-10a expression reacquire the mesenchymal phenotype, which may impair the proliferation capacity in the liver, resulting in decreased intrahepatic metastatic nodules. Although EphA4 is the direct target of miR-10a, we further explored the pathway by which miR-10a and EphA4 affected cell adhesion. Bourgin et al.32 reported that EphA4 regulates dendritic spine remodeling by affecting β1-integrin signaling pathways. Davy and Robbins40 also suggested that Ephrin-A5 modulates cell adhesion and morphology in an integrin-dependent manner, and previous studies have indicated that EphA4 can interact with Ephrin-A5 and participate in signal transduction. Integrin is an α/β heterodimeric membrane protein that mediates the adhesion of cells to components of the ECM. The integrin β1 subunit is crucial for adhesion to fibronectin (FN),41 which is one important component of the ECM. We measured the protein level of β1-integrin and found that it was up-regulated by miR-10a inhibition or EphA4 overexpression. These observations suggest that miR-10a and EphA4 regulate cell adhesion by mediating the β1-integrin signaling pathway.

Serum alphafetoprotein (AFP) level over 100 ng/mL during hepatitis flare usually represents more extensive hepatocytolysis or bridging hepatic necrosis (Liver 1986; 6:133-7). Whether higher AFP levels during hepatitis flare are associated with greater reduction in HBsAg level during Nuc therapy is unknown. Patients and methods: The study included 217 chronic hepatitis B patients who had adequate AFP measurement during hepatitis B flare (ALT ≥ 5X ULN). HBsAg level was measured at baseline, 6 month and 12 month of Nuc therapy using Elecsys HBsAg II (Roche Diagnostics, Indianapolis, IN, USA). The

PCI-32765 nmr results were analyzed according to AFP levels (<20, 20-50, 50-100 and ≥ 100 ng/mL) and ALT levels (5-10X, 10-20X, > 20XULN), respectively, and compared with that of 44 CHB patients with ALT < 5X ULN. Results: The results (Table 1) showed the higher the AFP level during hepatitis flare, the greater the reduction in HBsAg level during Nuc therapy. The reduction in HBsAg level was also greater in patients with higher ALT levels. Stepwise multiple linear regression analysis showed that AFP level, not ALT level, was significantly associated with greater reduction in 6th month and 1st year

HBsAg levels. Conclusion: The increase of AFP during hepatitis B flare, reflecting more extensive hepatocytolysis and subsequent regeneration, contributes to greater reduction in HBsAg level during Nuc therapy. Log10 reduction in HBsAg level in patients with VX-809 mouse different AFP and ALT levels Linear trend of HBsAg Log reduction at 6th month by ALT and AFP are P=0.000, respectively. Linear trend of HBsAg Log reduction at 12th month by ALT and AFP are P=0.000, respectively. AFP: alphafetoprotein; ALT: alanine transaminase; ULN: upper limit of normal; HBsAg: hepatitis B surface antigen. Disclosures: Yun -Fan Liaw -

Advisory Committees or Review Panels: Roche; Grant/Research Support: Roche The following people have nothing to disclose: Rachel Wen-Juei medchemexpress Jeng, Yi-Cheng Chen, Ming-Ling Chang Background and Aim: Liver Stiffness (LS) measured by Fibros-can (transient elastography; TE) has been reported to correlate with fibrosis stages in various liver diseases. The purpose of antiviral treatment for chronic hepatitis B is a suppression of liver fibrosis progression and a reduction of the risk for hepato-cellular carcinoma (HCC). The aim of the present study was to evaluate the effect of antiviral treatment on LS and its correlation to hepatocarcinogenesis in chronic hepatitis B. Methods: LS (kPa) was measured by TE in 372 patients with chronic hepatitis B.

Significant differences in messenger RNA (mRNA) profiles (T stroma versus matched NT fibrous tissue) were evaluated at a protein level using a validating set which consisted of 40 FFPE ICC equally distributed in cases with or without recurrence (Table 1). IHC was done using TMA to reduce experimental noise. Finally, the prognostic value of selected proteins was estimated using clinical records and patient follow-up reports (Fig. 1). LCM was performed to isolate RNA from the stromal compartment of freshly frozen ICC tissues. For each ICC tumor, fibrous tissue from portal areas within the surrounding nontumor

liver was also isolated and used as a reference (Fig. 2A). Following hybridization on microarrays, the statistical Alvelestat purchase analysis focused on identifying genes for which expression was significantly altered selleck chemicals llc in the stroma of ICC. As shown in Fig. 2B, applying stringent criteria (P < 0.001 and fold change FC > 2) resulted in the identification of 1,073 nonredundant genes differentially expressed between the NT fibrous tissue and the T stroma, demonstrating that the stroma of

ICC displayed substantial genomic changes (Supporting Table 3). Thirty-one percent of the stromal signature included genes that were up-regulated relative to NT fibrous tissue. Supporting the gene selection, a hierarchical clustering analysis based on this signature efficiently discriminated the NT fibrous tissue from the T stroma (Fig. 2C). Fully supporting this observation, integrative genomics demonstrated that the LCM-derived stroma signature also discriminated cholangiocarcinoma tumors from surrounding NT livers in an independent

genomic dataset (GSE26566) established from whole MCE tissue sections (Fig. 2D). Further validating the enrichment of the stromal compartment by LCM, both up- and down-regulated genes were categorized into functional modules associated with the extracellular region, including ECM (Supporting Table 4F). Down-regulated genes were enriched in gene sets known to be down-regulated in liver cancers, including genes involved in metabolism (Supporting Table 4, Supporting Fig. 2). Up-regulated genes were related to entry into the cell cycle, ECM organization, and cell signaling pathways, namely, p38, p53, and TGFβ. Accordingly, the stroma signature of ICC coincided with a discrete enrichment of transcription factor (TF)-associated gene sets (Supporting Table 4D). Indeed, up-regulated genes were known to be transcriptionally regulated by E2F(s) and SMAD(s), two families of TF involved notably in the regulation of cell cycle and TGFβ signaling pathway, respectively. Down-regulated genes were regulated by hepatocyte nuclear factors known to control the expression of numerous metabolic genes (Supporting Table 4, Supporting Fig. 2). These results were confirmed by an unsupervised GSEA (Supporting Fig. 2).

Significant differences in messenger RNA (mRNA) profiles (T stroma versus matched NT fibrous tissue) were evaluated at a protein level using a validating set which consisted of 40 FFPE ICC equally distributed in cases with or without recurrence (Table 1). IHC was done using TMA to reduce experimental noise. Finally, the prognostic value of selected proteins was estimated using clinical records and patient follow-up reports (Fig. 1). LCM was performed to isolate RNA from the stromal compartment of freshly frozen ICC tissues. For each ICC tumor, fibrous tissue from portal areas within the surrounding nontumor

liver was also isolated and used as a reference (Fig. 2A). Following hybridization on microarrays, the statistical MLN0128 analysis focused on identifying genes for which expression was significantly altered buy AZD2014 in the stroma of ICC. As shown in Fig. 2B, applying stringent criteria (P < 0.001 and fold change FC > 2) resulted in the identification of 1,073 nonredundant genes differentially expressed between the NT fibrous tissue and the T stroma, demonstrating that the stroma of

ICC displayed substantial genomic changes (Supporting Table 3). Thirty-one percent of the stromal signature included genes that were up-regulated relative to NT fibrous tissue. Supporting the gene selection, a hierarchical clustering analysis based on this signature efficiently discriminated the NT fibrous tissue from the T stroma (Fig. 2C). Fully supporting this observation, integrative genomics demonstrated that the LCM-derived stroma signature also discriminated cholangiocarcinoma tumors from surrounding NT livers in an independent

genomic dataset (GSE26566) established from whole 上海皓元医药股份有限公司 tissue sections (Fig. 2D). Further validating the enrichment of the stromal compartment by LCM, both up- and down-regulated genes were categorized into functional modules associated with the extracellular region, including ECM (Supporting Table 4F). Down-regulated genes were enriched in gene sets known to be down-regulated in liver cancers, including genes involved in metabolism (Supporting Table 4, Supporting Fig. 2). Up-regulated genes were related to entry into the cell cycle, ECM organization, and cell signaling pathways, namely, p38, p53, and TGFβ. Accordingly, the stroma signature of ICC coincided with a discrete enrichment of transcription factor (TF)-associated gene sets (Supporting Table 4D). Indeed, up-regulated genes were known to be transcriptionally regulated by E2F(s) and SMAD(s), two families of TF involved notably in the regulation of cell cycle and TGFβ signaling pathway, respectively. Down-regulated genes were regulated by hepatocyte nuclear factors known to control the expression of numerous metabolic genes (Supporting Table 4, Supporting Fig. 2). These results were confirmed by an unsupervised GSEA (Supporting Fig. 2).

15 Silencing of the MAT2A gene reduces HSC activation and suppresses cellular proliferation,15 thereby indicating that regulation of this gene may be important in

determining HSC phenotype. The aim of this study was to examine the molecular mechanisms responsible for the transcriptional regulation of the MAT2A gene in quiescent and activated HSCs. We demonstrate for the first time that the PPARγ transcription factor exerts a strong, negative regulatory control on MAT2A transcription in quiescent HSCs, and loss of PPARγ activity allows positive regulators such as PPARβ to induce MAT2A during HSC activation. α-SMA, α-smooth muscle actin; Adv, adenoviral; b2A, PD-0332991 ic50 basal MAT2A promoter; BDL, bile duct ligation; C/EBP, CCAAT/enhancer-binding protein; ChIP, chromatin immunoprecipitation; EMSA, electrophoretic mobility-shift assay; GFP, green fluorescent protein; HSC, hepatic HCS assay stellate cell; MAT, methionine adenosyltransferase; mRNA, messenger RNA; PCR, polymerase chain reaction; PPAR, peroxisome proliferator-activated receptor; PPRE, PPAR

response element; RSG, rosiglitazone; RT-PCR, reverse-transcription polymerase chain reaction; SAM, S-adenosyl methionine; siRNA, small interfering RNA. The use of animals in this study was approved by the Institutional Animal Care and Use Committee of the University of Southern California. HSCs were isolated from normal male Wistar rats or Wistar rats undergoing sham operation or BDL for 10 days by the Non-Parenchymal Liver Cell Core of the Southern California Research Center for Alcoholic Liver and Pancreatic Diseases and Cirrhosis medchemexpress as described.16 The viability (trypan blue exclusion) and the purity

of isolated HSCs (ultraviolet-excited fluorescence microscopy), exceeded 95%. Normal HSCs were culture-activated on plastic dishes until day 5. Sham and BDL HSCs were plated in 2% fetal bovine serum containing low-glucose Dulbecco’s modified Eagle’s medium on plastic dishes for 16 hours.15 The activated rat HSC cell line, BSC,17 was kindly provided by Dr. Hidekazu Tsukamoto at the University of Southern California. Rat BSC cells (0.4 × 104 per cm2) or day 5 culture-activated primary rat HSCs (5 × 104 per cm2) were treated with 50 μM or 10 μM of RSG,18 respectively (Cayman Chemical, Ann Arbor, MI) or dimethyl sulfoxide (control) for 48 hours. Plasmid or small interfering RNA (siRNA) transfections were performed during the last 24 hours of RSG treatment. In experiments involving a combination of plasmid and siRNA transfections, cells were maintained in RSG-containing medium for 72 hours during which siRNA and plasmid were sequentially transfected for the last 48 and 24 hours, respectively. The MAT2A promoter fragment (accession ID AB000717.2)19 was cloned into pGL3-Basic luciferase vector (Promega, Madison, WI).

15 Therefore, we also studied fibrogenesis by measuring mRNA expression of collagen and metalloprotease inhibitor (Timp 1), which decreased in p38α KO after they underwent BDL (Fig. 4D), showing that these KO mice exhibited a lower profibrotic stage. Moreover, collagen deposition in the liver by the Sirius Red staining method showed that p38α KO mice did not exhibit more fibrosis than WT mice in chronic cholestasis (Fig. 4E,F). Consequently, liver fibrosis does not seem to account for the reduced life span of p38α KO BDL mice. Albumin is considered a marker of hepatic function, and hence a decrease in its synthesis

could indicate impairment of the liver capacity for protein synthesis. p38α KO sham mice already showed decreased albumin mRNA levels before inducing the illness (Fig.

5A). In WT mice, the decrease in albumin mRNA expression began when BDL Selleck JNK inhibitor was performed, so the reduction in the albumin mRNA levels was seen at 12 days of cholestasis, and kept on descending until 28 days (Fig. 5A). In the p38α KO group, mRNA expression of albumin check details remained at the same low level during evolution of the illness, showing also no significant differences with the p38α sham group at 12 and 28 days (Fig. 5A). Albumin immunohistochemical staining showed the same profile (Fig. 5B). Since activation of p70 S6 kinase and subsequent phosphorylation of S6 ribosomal protein are involved in protein synthesis MCE and are downstream MAPK, we assessed activation of this pathway. Figure 6 and Supporting Fig. S6 show significantly reduced phosphorylation of p70 S6 kinase and S6 only in p38-deficient mice after BDL. Since endoplasmic reticulum stress might also contribute to the reduced

albumin synthesis, we measured GADD 153 and phosphorylation of eIF2a. Supporting Fig. S7 shows that liver-specific p38-deficient mice did not exhibit more endoplasmic reticulum stress than WT mice. On the other hand, looking for cellular structure alterations we investigated HSP27, a phosphorylation target of MK2, and found a significant increase (P < 0.01) in phospho-HSP27 by western blotting only in BDL WT mice but not in p38α KO mice (Fig. 5C; Supporting Fig. S3). Interestingly, p38α KO BDL mice had higher expression of HSP27 in comparison with WT BDL mice (Fig. 5C). This result was confirmed by confocal image analysis (Fig. 5D,E). At this point, considering all the parameters that were indicating that p38α KO BDL mice exhibited worse liver conditions and could suffer from the illness more than the WT BDL mice, we decided to study the evolution of hepatomegaly and cell size in the progress of the illness. Comparing the hepatocyte size at the very beginning, we found differences between WT sham and p38α KO sham (Fig. 6A). In addition, when mice underwent BDL a different phenomenon was observed. In a WT liver, cell growth tried to compensate for liver injury and loss of function.

Further studies are needed 1, in regions with different JQ1 ic50 patterns and frequencies of resistance to confirm these findings, and 2, to examine whether Grade A success is maintained with hybrid therapy shorter than 14 days. “
“Previous studies reported an epidemiological association between CagA-positive H. pylori

strains and pre-eclampsia. As antibodies anti-CagA cross-react with endothelial cells and trophoblast cells show an endothelial phenotypic profile, we hypothesized that anti-CagA antibodies may recognize antigens of cytotrophoblast cells, thus impairing their function. Placenta samples were obtained from healthy women. Cytotrophoblast cells were cultured in a medium containing increasing concentration of polyclonal anti-CagA antibodies. Binding of anti-CagA antibodies to cytotrophoblast cells was evaluated by cell ELISA and immunofluorescence assay. Invasive potential of those cells was assessed by an invasion culture system and by measuring of MMP-2. Protein sequencing was performed on antigens precipitated by anti-CagA antibodies. Measurement of phosphorylated ERK expression and NF-kB DNA-binding activity in trophoblast cells incubated with anti-CagA or irrelevant antibodies

was also performed. Anti-CagA antibodies recognized β-actin of cytotrophoblast cells, showing a dose-dependent binding. this website Incubation of cytotrophoblast cells with increasing doses of anti-CagA antibodies significantly reduced their invasiveness and determined 上海皓元 a significant decrease in phosphorylated ERK expression and a reduced NF-kB translocation activity. This study shows that anti-CagA antibodies recognize β-actin of cytotrophoblast cells, reducing their invasiveness ability, possibly giving a biological explanation for the epidemiological association. “
“Background:  Growth of Helicobacter pyloriin vitro depends on supplementation of the medium with blood or serum. However, these supplements often require frozen storage and can show batch-to-batch variation, resulting in differences

in bacterial growth. In this study, we introduce the use of a commercially available, lipid-rich supplement called AlbuMAX II® (Gibco BRL, Grand Island, NY, USA) for use as a serum/blood replacement for H. pylori culture. Materials and Methods:  The growth of H. pylori on solid and liquid media was examined by comparing growth after supplementation with horse blood, fetal calf serum, β-cyclodextrin or AlbuMAX II® (Gibco BRL). Human gastric adenocarcinoma (AGS) cellular responses to H. pylori were measured by NF-κB luciferase assays and IL-8 ELISA. Results:  We show that the growth of H. pylori on both solid and liquid media containing AlbuMAX II® (Gibco BRL) were comparable to levels obtained on blood agar or liquid media supplemented with serum. Growth was consistently higher in media supplemented with AlbuMAX II® (Gibco BRL) than media containing β-cyclodextrin.

Regarding products already

authorized, but with added changes in the manufacturing process, the main requirement was that the previous product had to be used as a control in the pharmacokinetic trial. All in all, these early guidelines appear to us still valid and are able to guarantee with good likelihood full efficacy and safety of new FVIII products. Until the early 1990s, general knowledge see more on the natural history of the development of FVIII inhibitory alloantibodies was that this complication develops afresh in up to 35% of newly diagnosed patients (PUPs) at an early age of 2 to 3 years, more frequently after 10 to 20 days of exposure to FVIII, less frequently between selleck inhibitor 20 and 50 exposures and seldom in multiply treated patients3. PTPs with severe haemophilia who had multiple exposures to FVIII (usually

defined 100–150 lifetime or more) develop inhibitors at a small rate throughout life (less than 10 inhibitors per 1000 treatment years) [3-5]. This widely accepted knowledge on the natural history of FVIII inhibitors was challenged in the early 1990s, when an outbreak of inhibitors occurred in Belgium and the Netherlands in PTPs who had changed their routinely used plasma-derived FVIII for a newly manufactured product. A higher than expected incidence of clinically relevant FVIII inhibitors was independently detected in Belgian and Dutch patients, who previously had at least 200 days of FVIII exposure. In the Belgian cohort of 109 patients, the incidence was 66 per 1000 patient-years of observation, in the Dutch cohort of 144 patients 20 per 1000 patient-years. These incidences compare unfavourably with the historical incidences observed MCE公司 in PTPs,

always smaller than 10 per 1000 [3-5]. This outbreak in PTPs remained isolated and was shown to be caused by that product with peculiar physicochemical features related to methods used for fractionation and viral inactivation, and inhibitors disappeared spontaneously or after immune tolerance induction when patients stopped the incriminated product [6, 7]. Yet, this observation marked a milestone in the history of development of clinical guidelines, because it did turn from pathogen to inhibitor-risk the focus of regulatory agencies, which became newly concerned that new fractionation and viral inactivation methods would trigger the development of FVIII inhibitors in tolerant patients previously treated multiple times. The Belgian–Dutch epidemics led to the decision that PTPs were the most appropriate patient population to assess the immunogenicity of new FVIII products, and hence to a revision of the CPMP/BPWG/198/95, approved in October 2000.

Regarding products already

authorized, but with added changes in the manufacturing process, the main requirement was that the previous product had to be used as a control in the pharmacokinetic trial. All in all, these early guidelines appear to us still valid and are able to guarantee with good likelihood full efficacy and safety of new FVIII products. Until the early 1990s, general knowledge PF-02341066 order on the natural history of the development of FVIII inhibitory alloantibodies was that this complication develops afresh in up to 35% of newly diagnosed patients (PUPs) at an early age of 2 to 3 years, more frequently after 10 to 20 days of exposure to FVIII, less frequently between selleck products 20 and 50 exposures and seldom in multiply treated patients3. PTPs with severe haemophilia who had multiple exposures to FVIII (usually

defined 100–150 lifetime or more) develop inhibitors at a small rate throughout life (less than 10 inhibitors per 1000 treatment years) [3-5]. This widely accepted knowledge on the natural history of FVIII inhibitors was challenged in the early 1990s, when an outbreak of inhibitors occurred in Belgium and the Netherlands in PTPs who had changed their routinely used plasma-derived FVIII for a newly manufactured product. A higher than expected incidence of clinically relevant FVIII inhibitors was independently detected in Belgian and Dutch patients, who previously had at least 200 days of FVIII exposure. In the Belgian cohort of 109 patients, the incidence was 66 per 1000 patient-years of observation, in the Dutch cohort of 144 patients 20 per 1000 patient-years. These incidences compare unfavourably with the historical incidences observed MCE公司 in PTPs,

always smaller than 10 per 1000 [3-5]. This outbreak in PTPs remained isolated and was shown to be caused by that product with peculiar physicochemical features related to methods used for fractionation and viral inactivation, and inhibitors disappeared spontaneously or after immune tolerance induction when patients stopped the incriminated product [6, 7]. Yet, this observation marked a milestone in the history of development of clinical guidelines, because it did turn from pathogen to inhibitor-risk the focus of regulatory agencies, which became newly concerned that new fractionation and viral inactivation methods would trigger the development of FVIII inhibitors in tolerant patients previously treated multiple times. The Belgian–Dutch epidemics led to the decision that PTPs were the most appropriate patient population to assess the immunogenicity of new FVIII products, and hence to a revision of the CPMP/BPWG/198/95, approved in October 2000.

85-0.98) for TE, 0.91 (95% Cl: 0.83-1.00) for PQE and 0.91 (95% Cl: 0.84-0.99) for TE and 0.88 (95% CI: 0.80-0.96) for PQE and 0.85 (95% Cl: 0.73-0.97) for TE when comparing F0 versus F1-F4, F0-F1 versus F2- F4, F0-F2 versus F3-F4 and F0-F3 versus F4, respectively. Differences among PQE and TE AUCs were not statistically significant. CONCLUSIONS: This study shows that PQE is a reliable noninvasive method to assess LF, with a diagnostic performance not significantly different

Selleckchem BTK inhibitor from TE. Compared to TE, PQE has the advantage of compute measurements visualizing in real-time the explored area. Disclosures: Pietro Andreone – Advisory Committees or Review Panels: Roche, Janssen-Cilag, Gilead, MSD/Schering-Plough; Grant/Research Support: Roche, Gilead; Speaking and Teaching: Roche, MSD/Schering-Plough The following people have nothing to disclose: Erica Fiorini, Fabio Conti, Elena Mazzotta, Chiara De Molo, Silvia Righi, Gabriella Verucchi, Antonietta D’Errico, Marco Lenzi, Claudia Sama, Carla Serra Background & Aim: Acoustic NSC 683864 price radiation force impulse (ARFI) imaging is a novel non-invasive ultrasound-based method for the evaluation of liver fibrosis and cirrhosis. The relevance of ARFI imaging for outcome of patients with liver cirrhosis has not been established

so far. Methods: In this prospective study, consecutive patients with established liver cirrhosis from different etiologies underwent ARFI imaging of the liver and spleen and transient elastography (TE) of the liver. Liver and spleen stiffness measurements were compared with overall survival time or time to transplantation using Cox regression analyses. Results: 158 patients (mean age: 54± 11; male gender: 66.5%; Child-Pugh score B/C: 46%) were included in the study. The median liver and spleen stiffness measured by ARFI was 3.0 m/s and 3.7 m/s, respectively. 上海皓元 The median liver stiffness measured by TE was 36.3 kPa. The mean duration of follow-up was 629±390 days. During the follow-up

period 44/158 patients died and 25/158 underwent liver transplantation. There was a significant association between stiffness values obtained with all three methods and survival, i. e. patients with higher stiffness values showed shorter survival times. However, in a multivariate Cox regression analysis that included all three modalities, only spleen stiffness measured by ARFI was independently associated with survival (p=0.008; HR: 2.1, 95% Cl: 1.2-3.6). The AUROC of spleen stiffness measurements by ARFI for the prediction of survival was 0.64 (p=0.003). Conclusions: Spleen stiffness measured by ARFI predicts survival in patients with liver cirrhosis. Disclosures: Christoph Sarrazin – Advisory Committees or Review Panels: Boehringer Ingelheim, Vertex, Janssen, Merck/MSD, Gilead, Roche, Boehringer Ingelheim, Achillion, JaPharmaceuticals, Merck & Co.