23 The percentage of central obesity doubled in men (from 122% t

23 The percentage of central obesity doubled in men (from 12.2% to 26.7%) but remained stable in women in the most recent decade.24 The

local obesity trend may explain the higher local learn more rate of colorectal cancer in males than females. However, this cannot explain the decreasing risk of colorectal cancer in the younger population in Hong Kong. Hormonal replacement was found to decrease colorectal cancer.25,26 The increasing use of hormonal replacement in postmenopausal women may be one of the causes of decreasing risk of colorectal cancer in those females around 60 years of age. Use of oral contraceptives has been shown to be associated with decreased risk of colorectal cancer27 and this may be partly accountable for the decreasing risk of colorectal cancer in young females observed in the present study. A recent study found that colorectal cancer in those aged 40 years and younger were

in general more poorly differentiated and advanced in staging.28 This suggests that the nature of the colorectal cancer in young people may be different from Cell Cycle inhibitor those in older populations, and so may their pathogenesis. If this is the case, the effect of westernization and other causal factors on the risk of colorectal cancer among young people may be different from older populations. Whether this is an explanation of the decrease in incidence from 1983–2006 in the younger males and females, but rising incidence in 上海皓元医药股份有限公司 older populations, requires further study. In conclusion, the rising incidence of colorectal cancer in Hong Kong is confined to the predominantly older and male population rather than the younger age groups. The reason for the declining incidence of colorectal cancer in the younger age groups needs further exploration. “
“Aim:  The factors associated with hepatitis recurrence after discontinuation

of nucleos(t)ide analogs (NAs) in patients with chronic hepatitis B were analyzed to predict the risk of relapse more accurately. Methods:  A total of 126 patients who discontinued NA therapy were recruited retrospectively. The clinical conditions of a successful discontinuation were set as alanine aminotransferase (ALT) below 30 IU/L and serum hepatitis B virus (HBV) DNA below 4.0 log copies/mL. Results:  Relapse of hepatitis B were judged to occur when maximal serum ALT became higher than 79 IU/L or when maximal serum HBV DNA surpassed 5.7 log copies/mL following NA discontinuation since these values corresponded with mean values of ALT (30 IU/L) and HBV DNA (4.0 log copies/mL), respectively. At least 90% of patients with either detectable hepatitis B e antigen or serum HBV DNA higher than 3.0 log copies/mL at the time of NA discontinuation relapsed within one year. In the remaining patients, higher levels of both hepatitis B surface and core-related antigens at the time of discontinuation, as well as a shorter course of NA treatment, were significantly associated with relapse by multivariate analysis.

2 months versus not reached; recurrence, 8750% versus 613%; P =

2 months versus not reached; recurrence, 87.50% versus 61.3%; P = 0.073) and while there was no significant difference

among recurrence rates of groups I and III (P = 0.241) (Fig. 4B). Compared with group IV, patients in the other three groups had significantly shorter TTR and higher recurrence rates (P < 0.001) (Fig. 4B). The most effective therapeutic options for HCC offering a favorable prognosis are hepatectomy and liver transplantation. However, even such presumably curative surgery does not guarantee full recovery, and this failure is due in large part to the high incidence of recurrence (50%-70% at 5 years).2 The most significant reason for the unsatisfactory therapeutic ICG-001 in vivo outcome is residual micrometastases formed prior to resection or dissemination of tumor cells during surgical manipulation.25 Unfortunately, routine diagnostic approaches are thus far unable to identify the HCC patient subpopulation at high risk of developing micrometastases preoperatively,17 as well as the tumor cells that escape or invade into peripheral blood during surgery. Recent clinical studies have provided evidence that CTCs may directly participate in the metastasis cascade in various types of malignancies.26

The prognostic significance of CTCs has been widely reported in metastatic breast, colon, and prostate cancers. However, the presence of CTCs in the circulation is a necessary but insufficient condition for the initiation of metastasis, since only a minority of dispersed cells possessing stem cell–like properties MCE公司 is capable NVP-AUY922 order of reseeding the tissue of origin or metastasizing to distant organs.3, 6 Therefore, identifying the stem cell–like CTC subset with such properties would provide more clinically relevant prognostic

information than total CTC counts. In the present study, we found that patients with preoperative CTC7.5 levels of ≥2 EpCAM+ CTCs suffered significantly earlier recurrence (within 1 year) than patients with lower levels. A preoperative EpCAM+ CTC7.5 ≥2 was significantly associated with aggressive HCC phenotypes. Moreover, EpCAM+ CTCs displayed stem cell–like traits. Based on these data, we inferred that EpCAM+ CTCs with stem cell–like phenotypes might represent a more aggressive subset of CTCs. These cells were more likely to invade the circulatory system, survive, and finally seed in orthotopic or distant sites, leading to local recurrence or distant metastasis. Thus, the preoperative detection of EpCAM+ CTCs might serve as a novel indicator reflecting the micrometastatic status and recurrence risk of HCC patients in a real-time manner, which in turn could provide a therapeutic window and target before the appearance of bona fide recurrence. According to the CSC hypothesis, a small population of cells possessing stem cell–like traits is the driving force of tumor progression and resistance to classical therapies.

There is good evidence supporting an increasing incidence of Eosi

There is good evidence supporting an increasing incidence of Eosinophilic Oesophagitis (EO). Successful foreign body and food bolus removal may depend on the method used, the choice of device, and the experience level of the endoscopist, as well as patient factors. Aim: We aimed to investigate the clinical characteristics, type of foreign body ingested and presence of underlying pathology in patients presenting to a tertiary hospital

emergency department who then proceeded to Ibrutinib endoscopy. Methods: Retrospective review of patients presenting to the Emergency Department with oesophageal foreign body impaction from 2007 to 2010 was performed. Demographic and clinical information was collected from medical records, endoscopy and laboratory database. Results: Episodes of FB ingestion (n = 101) were identified. Fifty-five percent were unintentional single presentations most commonly OFBI. Recurrent presentations occurred in 47%, of which 53% had underlying psychiatric diagnoses. Underlying pathology in this group included benign strictures in 8.5%, malignant strictures in 8.5% and EO in 27%. The

single most commonly ingested FB were knives in 26%. In the unintentional single presentations underlying pathology was found in 64.8%. Overall success rate for endoscopic removal JNK inhibitor was 58% in the intentional ingestion group, and 97% in the unintentional. Failure was due to location and type of FB and 13.9% proceeded to surgery. Conclusions: There was an increasing trend each year of FB ingestion in both groups with an increasing incidence in diagnosis of EO. While OFBI is most common there is an increasing trend in a relatively small cohort of patients with psychiatric illness to present repeatedly with FB ingestion. M ROBERTSON,1 W CHUNG,1 R TERBAH,1 R BOYAPATI,1 A MAJUMDAR,1 S LONTOS1 1Department

of Gastroenterology and Liver Transplant Unit, Austin Health, Heidelberg, Victoria Introduction: Coffee 上海皓元医药股份有限公司 ground vomiting (CGV) is defined as the passage of black material which is assumed to be blood. Its presence implies that bleeding has ceased or has been relatively modest. It is therefore considered as low to medium risk upper gastrointestinal bleeding (UGIB) compared to frank haematamesis or melaena. There is very little data on whether presentation with CGV correlates with less severe findings at endoscopy or superior clinical outcomes. Aim: To evaluate findings at endoscopy and clinical outcomes in patients presenting with coffee ground vomiting. Methods: ICD-10 codes were used to identify all patients presenting with a primary diagnosis of UGIB requiring endoscopy at the Austin Hospital over a 36-month period from 2010 to 2012.

9% of migraineurs reported opioid use in the past 3 months for co

9% of migraineurs reported opioid use in the past 3 months for control. Of the opioid users, 16.6% met criteria for probable opioid dependence, representing 2.6% of the total sample of migraineurs. The prevalence of anxiety and depression was highest among current opioid users with probable dependence.[19] Recent studies in neuroimaging and pharmacogenetics suggest an overlap MAPK inhibitor between the pathophysiological mechanisms of MOH and substance-related disorders.[53] Functional magnetic resonance imaging data during the execution of a decision-making under risk paradigm found that MOH patients showed

dysfunction in the mesocorticolimbic dopamine circuit – particularly in the ventromedial prefrontal cortex and in the substantia nigra/ventral tegmental complex – when compared with several control groups. The ventromedial prefrontal cortex dysfunctions appear to be reversible based on comparison to a control group of MOH patients 6 months after drug withdrawal. In contrast, the substantia nigra/central tegmental area complete dysfunctions persist even 6 months after withdrawal, based on a comparison to CM and non-migraine controls.[54] Moreover, headache sufferers with personality disorders (PDs), in particular cluster B entities, may act out particular behaviors, such as defiance of limits regarding medication usage, battles of control over treatment, and attitudes of entitlement regarding

pain control, resulting in medication overuse.[55] DSM-5 defines a personality disorder as IWR-1 “an enduring pattern of inner experience and behavior that deviates markedly from the expectations of the individual’s 上海皓元医药股份有限公司 culture, is pervasive and inflexible, has an onset in adolescence or early adulthood, is stable over time, and leads to distress or impairment.”[52] PDs continue to be grouped in 3 clusters: A (paranoid, schizoid, and schizotypal), B (antisocial, borderline, histrionic, and narcissistic), and C (avoidant, dependent, and obsessive–compulsive). The cluster B disorders are marked by self-serving traits that often

emerge in the doctor–patient relationship, such as deceit (antisocial), dramatic mood swings from idealizing to intense anger at the physician (borderline), seductiveness and drama (histrionic), and entitlement (narcissistic). Of potential interest is a new PD diagnosis in DSM-5: “personality change due to another medical condition,” which refers to medically related persistent personality changes that deviate significantly from the individual’s previous characteristic personality pattern. In a sample of 267 patients who completed a multidisciplinary inpatient treatment program, MOH was more common in those with a PD diagnosis (62%) than those with no PD (38%).[55] The presence of borderline PD, moderate-severe depression, and MOH may be an unfortunate trifecta associated with poor outcomes from outpatient treatment programs.

6d–f) In addition, significantly increased integrin expression w

6d–f). In addition, significantly increased integrin expression was also detected under subconfluent culture conditions (Fig. 6d–f). IN THE PRESENT study, little or no expression of the β6, β4 and α3 integrins was immunohistochemically shown in CoCC, whereas high expression levels of these integrins were evident in CCC. Integrin mRNA levels were high in most of the CCC cell lines, but they were almost undetectable in most Selleckchem Y27632 of the HCC cell lines, as previously reported for integrin β6.[21] These

results indicated that the expression levels of these integrins, including both the injury-induced type integrin β6 and bile duct-specific integrins β4 and α3 are downregulated in CoCC in contrast to their overexpression in CCC. Furthermore, immunostaining for integrins, PI3K inhibitor particularly integrin β4, revealed high specificity and a highly positive predictive value with regard to differentiation between CoCC and CCC, indicating a diagnostic value of the present immunohistochemical findings. An algorithm for the differential diagnosis of CoCC, CCC and HCC using immunohistochemistry is shown in Figure 7. The high integrin expression frequently encountered in CCC was not related to the gross type and histological differentiation grade of the tumor, even though the peripheral mass-forming type of CCC has been shown to have histological features similar to CoCC.

The aberrant expression of the β6 and β4 integrins, with three different expression patterns, cytoplasmic, cell membrane

上海皓元 and basal lamina types, in CCC was also demonstrated in the present study, though its significance remains to be clarified. The expression of these integrins in CoCC resembled the expression of integrins in HCC. In addition, the CoCC samples in the present study were significantly associated with chronic viral hepatitis and liver cirrhosis, which is well known in HCC. CoCC exhibits a biliary phenotype with CK7 and CK19 positivity, as does CCC, in addition to a microtubular structure resembling cholangioles or canals of Hering, but it also has been shown to have some intermediate features with a trabecular structure and AFP positivity similar to HCC. In addition, CoCC has been reported to show hepatic stem cell/progenitor cell features that are suggestive of hepatic progenitor cell origin.[4, 30, 31] The low expression of integrins in CoCC, similar to that in HCC in the present study, may be associated with intermediate phenotypes of CoCC cells that are possibly derived from hepatic progenitor cells. In fact, the downregulation of integrin expression in CoCC components and HCC components in contrast to the enhanced expression in CCC components was also observed in classical CHC, the histogenesis of which has been suggested to be associated with hepatic progenitor cells.

6d–f) In addition, significantly increased integrin expression w

6d–f). In addition, significantly increased integrin expression was also detected under subconfluent culture conditions (Fig. 6d–f). IN THE PRESENT study, little or no expression of the β6, β4 and α3 integrins was immunohistochemically shown in CoCC, whereas high expression levels of these integrins were evident in CCC. Integrin mRNA levels were high in most of the CCC cell lines, but they were almost undetectable in most Trichostatin A datasheet of the HCC cell lines, as previously reported for integrin β6.[21] These

results indicated that the expression levels of these integrins, including both the injury-induced type integrin β6 and bile duct-specific integrins β4 and α3 are downregulated in CoCC in contrast to their overexpression in CCC. Furthermore, immunostaining for integrins, Metformin clinical trial particularly integrin β4, revealed high specificity and a highly positive predictive value with regard to differentiation between CoCC and CCC, indicating a diagnostic value of the present immunohistochemical findings. An algorithm for the differential diagnosis of CoCC, CCC and HCC using immunohistochemistry is shown in Figure 7. The high integrin expression frequently encountered in CCC was not related to the gross type and histological differentiation grade of the tumor, even though the peripheral mass-forming type of CCC has been shown to have histological features similar to CoCC.

The aberrant expression of the β6 and β4 integrins, with three different expression patterns, cytoplasmic, cell membrane

MCE公司 and basal lamina types, in CCC was also demonstrated in the present study, though its significance remains to be clarified. The expression of these integrins in CoCC resembled the expression of integrins in HCC. In addition, the CoCC samples in the present study were significantly associated with chronic viral hepatitis and liver cirrhosis, which is well known in HCC. CoCC exhibits a biliary phenotype with CK7 and CK19 positivity, as does CCC, in addition to a microtubular structure resembling cholangioles or canals of Hering, but it also has been shown to have some intermediate features with a trabecular structure and AFP positivity similar to HCC. In addition, CoCC has been reported to show hepatic stem cell/progenitor cell features that are suggestive of hepatic progenitor cell origin.[4, 30, 31] The low expression of integrins in CoCC, similar to that in HCC in the present study, may be associated with intermediate phenotypes of CoCC cells that are possibly derived from hepatic progenitor cells. In fact, the downregulation of integrin expression in CoCC components and HCC components in contrast to the enhanced expression in CCC components was also observed in classical CHC, the histogenesis of which has been suggested to be associated with hepatic progenitor cells.

04), lower degree of fibrosis (37% × 56% p 0,05) and a trend to a

04), lower degree of fibrosis (37% × 56% p 0,05) and a trend to a higher frequency of associated autoimmune diseases (39% × 23% p 0,06 Paclitaxel mw ). Anti-SLA was related to lower frequency of biochemical response (48% × 74% p 0,014 ). Anti-LC1 patients presented more frequently with liver failure at presentation (67% × 29% p 0,07) and a trend to higher gammaglobulin levels

(3,9 ±1,4 × 2,8 ±1,2 p 0,06). Comparative analysis of patients with positivity or negativity to anti-Sp100 and anti-gp210 revealed that both were related to older age (45±18 × 32±17 p 0,04 to Sp100 and 42±18 × 32±17 p 0,04 to gp210) and to the diagnosis of OS (56% × 10% p 0,002 to anti-Sp100 and 40% × 9% p 0,005 to anti-gp210). Conclusion: NCAs are promising markers for the evaluation of AIH and OS patients. Besides having a diagnostic role in some cases, they can help in planning strategies for monitoring treatment, contributing for the early identification of more difficult cases and optimization of treatment. Disclosures: check details The following people have nothing to disclose: Elze M. Oliveira, Patricia M.

Oliveira, Ana Cristina A. Feldner, Valéria P. Lanzoni, Renata M. Perez, Ales-sandra Dellavance, Luis Eduardo C. Andrade, Antonio Eduardo B. Silva, Maria Lucia Ferraz INTRODUCTION: Autoimmune hepatitis (AIH) is a disease of unknown aetiology, characterized by a loss of tolerance toward liver antigens resulting in the progressive destruction of the hepatic parenchyma. It is known as a disease mediated by T-cells, with an important

contribution from CD4+ Th1 cells. However, recent studies from small cohorts MCE公司 of AIH patients refractory to conventional treatment have reported successful rescue therapy through B cells depletion with Rituximab, an anti-CD20 monoclonal antibody. AIM: To study the outcome of B-cell depletion in an animal model of AIH and understand the mechanisms underlying the remission.METHODS: A model of AIH in female C57BL/6 mice xenoimmunized with DNA coding for human liver antigens was used. AIH mice were treated with 1 injection of an anti-CD20 monoclonal antibody (Genentech) at the peak of liver inflammation. Serum amino-transferase levels, IP10 expression, circulating B cell levels, autoantibody levels, and total IgG levels were monitored. Liver inflammation and spleen architecture were evaluated. Spleen and liver cell phenotypes were characterized by flow cytometry. B cell function as APCs was analyzed in a lymphoproliferative assay against liver antigens.RESULTS: In the AIH mouse model, B cells were found in liver infiltrates, secreted IFN-γ and TNF-α and proliferated to autoantigen. A single dose of anti-CD20 resulted in more than 95% decrease in circulating B cells (CD45+CD19+) followed by a progressive reconstitution 40 days after injection. A drastic reduction of liver inflammation was observed (p<0.0001), accompanied by a significant reduction of ALT levels (p=0.

The patients included 45 men and 155 women, and the median age wa

The patients included 45 men and 155 women, and the median age was 63 years. Two hundred and eighty-one treatments were performed for these patients, PS341 as follows: cyst aspiration sclerotherapy (AS) in 152 cases, cyst fenestration (FN) in 53, liver

resection (LR) in 44, liver transplantation (LT) in 13 and other treatments in 19. For cases of type I PLD (mild form) according to Gigot’s classification, the therapeutic effects of AS, FN and LR were similar. For type II (moderate form), LT demonstrated the best therapeutic effects, followed by LR and FN. For type III (severe form), the effects of LT were the best. The incidences of complications were 23.0% in AS, 28.4% in FN, 31.8% in LR and 61.5% in LT. Considering the therapeutic effects and complications, AS, LR and LT showed good results for type I, type II and type III PLD,

respectively. However, LT for PLD was performed in a small number of patients. In Japan, the transplantation therapy is expected to be common in the future. “
“Only humans and chimpanzees are susceptible to chronic infection by hepatitis C virus (HCV). MK-1775 chemical structure The restricted species tropism of HCV is determined by distinct host factor requirements at different steps of the viral life cycle. In addition, effective innate immune targeting precludes efficient propagation of HCV in nonhuman cells. Species-specificity of HCV host factor usage for cell entry and virus release has been explored. However, the reason for inefficient HCV RNA replication efficiency in mouse liver cells remains elusive. To address this, we generated novel mouse liver-derived cell lines with specific lesions in mitochondrial antiviral signaling protein (MAVS), interferon regulatory factor 3 (IRF3), or Interferon-α/β receptor (IFNAR) by in vivo immortalization. Blunted innate immune responses in these cells modestly increased HCV RNA replication. However, ectopic expression of liver-specific human

microRNA 122 (miR-122) further boosted RNA replication in all knockout cell lines. Remarkably, MAVS−/−miR-122 cells sustained vigorous HCV RNA replication, attaining levels comparable to the highly permissive human hepatoma cell line Huh-7.5. RNA replication was dependent on mouse 上海皓元医药股份有限公司 cyclophilin and phosphatidylinositol-4 kinase III alpha (PI4KIIIα) and was also observed after transfection of full-length viral RNA. Additionally, ectopic expression of either human or mouse apolipoprotein E (ApoE) was sufficient to permit release of infectious particles. Finally, expression of human entry cofactors rendered these cells permissive to HCV infection, thus confirming that all steps of the HCV replication cycle can be reconstituted in mouse liver-derived cells. Conclusion: Blunted innate immunity, abundant miR-122, and HCV entry factor expression permits propagation of HCV in mouse liver-derived cell lines.

The identified receptor tyrosine kinases (RTKs) mediate HCV

The identified receptor tyrosine kinases (RTKs) mediate HCV this website entry by regulating CD81-claudin-1 coreceptor associations and viral glycoprotein-dependent membrane fusion. These results identify RTKs as previously unknown HCV entry cofactors and show that tyrosine kinase inhibitors have substantial antiviral activity. Inhibition of RTK function may constitute a new approach for prevention and treatment of HCV infection. The current standard of care for chronic hepatitis C virus (HCV) is a combination therapy of pegylated interferon alpha (PEG-IFN-α) and ribavirin. However, treatment success is highly genotype dependent, and, at best, only 50% of infected individuals show

a sustained virological

response. Dabrafenib solubility dmso The recent approval of direct antivirals targeting the HCV NS3/4A protease [e.g., telaprevir (Vertex Pharmaceuticals, Cambridge, MA) and boceprevir (Merck, Whitehouse Station, NJ)] will significantly change the landscape of treatment for HCV. However, the low genetic barrier to resistance of these compounds suggests that the generation of drug-resistant mutants will be significant, and, therefore, direct acting antivirals will need to be used in combination with PEG-IFN-α/ribavirin therapy. Thus, the race continues to develop safer, cheaper therapeutic strategies. Entry into the host cell is a critical event in the viral life cycle, and, as such, it represents a promising target for antiviral therapy. Indeed, this strategy has recently been approved for the treatment of

human immunodeficiency virus (HIV) infection, in which binding of the HIV gp120 to the cellular coreceptor, CCR5, is antagonized by maraviroc (Pfizer, New York, NY), resulting in a block of viral entry. However, the development of such strategies requires an in-depth knowledge of the viral-host interactions, leading to viral entry. Considerable progress of late has been made in defining how HCV enters human hepatocytes. HCV entry is a multistep process and involves the viral envelope glycoproteins and at least four critical host cell receptors that are essential for efficient HCV entry (see below), although the sequence of events and cellular signals involved 上海皓元医药股份有限公司 in the entry process remain unresolved. Exciting new work published in Nature Medicine by Lupberger et al. has identified receptor tyrosine kinases (RTKs) as playing a pivotal role in assisting HCV entry. This work adds significantly to our understanding of the HCV entry process. As a number of RTK inhibitors are approved for clinical use, this discovery may translate into novel therapeutic strategies to combat HCV infection. In recent years, there has been extensive investigation into elucidating the precise mechanisms of HCV entry into hepatocytes.

e, boceprevir and telaprevir) is still conditioned by IFN respon

e., boceprevir and telaprevir) is still conditioned by IFN responsiveness. “
“Study purpose: The farnesoid-X-receptor (FXR) is a nuclear bile acid receptor involved in bile acid homeostasis, Talazoparib mouse hepatic and intestinal inflammation, liver fibrosis and cardiovascular disease. We studied the effect of short-term treatment with obeticholic acid (INT-747), a potent selective FXR agonist, on intrahepatic hemodynamic dysfunction and signaling pathways in different rat models of cirrhotic portal hypertension. Methods: Thioacetamide (TAA)-intoxicated and bile duct ligated (BDL) rats were used as models. After gavage of 2 doses of 30mg/kg INT-747 or vehicle within 24 hours,

in vivo hemodynamics were assessed. Additionally, we evaluated the direct effect of INT-747 on total intrahepatic www.selleckchem.com/products/MK-1775.html vascular resistance (IHVR) and intrahepatic vascular tone (endothelial dysfunction and hyperresponsiveness to methoxamine) by means of an in-situ liver perfusion system and on hepatic stellate cell contraction in vitro. FXR-expression and involved intrahepatic vasoactive pathways (e. g. endothelial nitric oxide synthase: eNOS, Rho-kinase, dimethylarginine dimethylaminohydrolase: DDAH) were analyzed by immunohistochemistry, RT-PCR or Western Blot. Results: In both cirrhotic models, FXR expression was heavily decreased. Immunohistochemically,

this coincided with a disappearance of the typical FXR hepatocytic medchemexpress nuclear staining pattern seen in healthy livers. Treatment with INT-747 in TAA and BDL reactivated the FXR downstream signaling pathway and decreased portal pressure without deleterious systemic hypotension (portal pressure decreased from 13.8 ± 0, 6 mm Hg to 11.6 ± 0, 8 mm Hg in TAA, P=0.045, n=14 and from 12.3 ± 0, 8 mm Hg to 10.1 ± 0, 6 mm Hg in BDL, P=0.037, n=15). This was related to a decrease in total intrahepatic vascular resistance during liver perfusion (relative decrease in IHVR after INT747 treatment in TAA: −8.06 ± 0.69%, P<0.001,

n=10 and in BDL: −21.8 ± 2.50%, P<0.001, n=10). In the perfused TAA and BDL cirrhotic liver, INT-747 improved endothelial vasorelaxation capacity but not hyperresponsiveness. In both groups, this was associated with an increased eNOS-activity which in TAA related to down-regulation of the Rho-kinase pathway and in BDL to up-regulation of DDAH-2.Furthermore, INT-747 induced a dose-dependent relaxation of cultured rat primary hepatic stellate cells in vitro. Conclusion: FXR-agonist INT-747 improves portal hypertension in 2 different rat models of cirrhosis by decreasing the IHVR. This hemodynamic effect relates to restoration of endothelial dysfunction by increased intrahep-atic eNOS-activity. The mechanisms of eNOS activity increase differ depending on the etiology of cirrhosis. Disclosures: Frederik Nevens – Grant/Research Support: Ipsen, Roche, MSD, Astellas, CAF The following people have nothing to disclose: Len D.