The average age was

The average age was Selleck Belinostat 50.3 years, ranging from 12 to 69 years. type B was the most commonly observed type of biliary

obstruction after liver transplantation, accounting for 47.3% (44/93), and type A was the least commonly observed type of biliary obstruction after liver transplantation, accounting for 9.7% (9/93). And type C accounted for 23.7% (22/93)and type D accounted for 19.3% (18/93). Conclusion: A new endoscopic classification of biliary obstruction after liver transplantation is proposed that might help in determining the proper candidates for treatment. Key Word(s): 1. Biliary obstruction; 2. Liver; 3. classification; 4. transplantation; Presenting Author: HONG CHANG Additional Authors: YONGHUI HUANG, WEI YAO, LI ZHANG, YUAN LI Corresponding Author: YONGHUI HUANG Affiliations: Peking University Third Hospital Objective: To evaluate

the feasibility and efficacy of Applications of a small -caliber transnasal endoscopy PF 01367338 for percutaneous endoscopic gastrostomy and gastrostomy tube replacement in patients with motor neuron disease (MND) or severe esophageal diseases. Methods: Between June 2005 and March 2012, in Peking University Third Hospital, 118 persom-times underwent percutaneous endoscopic gastrostomy (PEG) with the ‘pull’ method using conventional gastroscopy (69 cases) or a small-caliber transnasal endoscopy (49 cases), 44 persom-times underwent gastrostomy tube replacement using conventional endoscopy (37 cases) or through the abdominal-wall stoma with a small-caliber transnasal endoscopy (7 cases). Indications for PEG included MND, esophageal stricture, esophagotracheal Fistula, and anorexia nervosa. Results: PEG by ‘pull’ method achieved in 47 of 49 cases (95.92%) with small-caliber transnasal endoscopy (one faied becaused of dyspnea, one becaused of puncture failure), which achieved in 66 of 69 cases (95.65%) with traditionary endoscopy (3 patients failed because of dyspnea), There were no significant differences in the average procedure time between the two groups, but Vasopressin Receptor the patients in group of small-caliber transnasal endoscopy reported less discomfort

associated with the procedure. There were no complications of major hemorrhage, perforation or aspiration. Gastrostomy tube replacement achieved in 44 of 44 cases (100%). 7 of these underwent with a small-caliber transnasal endoscopy through the abdominal-wall stoma, and colonoscopy position made the procedure quick and easy, the average procedure time was 7 ± 1.5 min. Conclusion: Small -caliber transnasal endoscope reduces the discomfort of the procedure and is safer than conventional gastroscopy for PEG. Gastrostomy tube replacement through the abdominal-wall stoma with a small-caliber transnasal endoscopy was feasible, safe and simple procedure and reduced the pain and stress of patients. Key Word(s): 1. transnasal endoscopy; 2. PEG; 3.

Note the difference in units for HBV DNA levels In the current G

Note the difference in units for HBV DNA levels. In the current Guidelines and in Japan in general, HBV DNA is expressed as copies/mL, but elsewhere the unit IU/mL is used (IU stands for international units). The AASLD, EASL and APASL guidelines all use IU/mL. Table 10 shows conversion rates between IU/mL and copies/mL. For example, the general treatment cutoff of 2000 IU/mL is equivalent to 4.07 log copies/mL (conversion rate 5.82) using the TaqMan method (Roche). Note that conversion rates may differ between real-time PCR methods; for example,

the same treatment standard would be 3.83 log copies/mL (conversion rate 3.41) using the AccuGene method (Abbott). Further research is required into these discrepancies. TaqMan (Roche) (×5.82) 116 9.9×108 AccuGene (Abbott) (×3.41) 34 3.4×109 Recommendation Real-time PCR is recommended for HBV DNA quantification in the clinical setting. Ixazomib nmr HBsAg is an antigen within the HBV envelope that is present within the blood as the Dane particle as well as empty particles, small spherical particles and tubular particles, all of which are generated from covalently closed FDA approved Drug Library price circular DNA (cccDNA) in the hepatocytes, as shown in Figure 2. Qualitative reagents have traditionally been used for measuring HBsAg and for the diagnosis of hepatitis B. But recent

years have seen the development of a number of new quantitative reagents with considerable

potential for prognosis and evaluation of therapeutic effects.[64, Y-27632 nmr 65] Table 11 lists reagents used for measuring HBsAg. Mono (two types) Mono (two types) Mono (various) Mono (two types) Mono (two types) Mono (various) Mono (two types) 0.1∼2000 C.O.I. 0.05∼250 IU/mL (manual/auto dilution) 0.03∼2500 IU/mL (auto dilution) 0.005∼150 IU/mL (auto dilution) Observations generated by qualitative reagents are expressed in terms of a cut-off index (COI), where a value of 1.0 or higher is deemed positive and higher measurements are semiquantitative, used for reference purposes. Common quantitative reagents include Architect (Abbott) and HISCL (Sysmex). Table 11 shows the threshold criteria and measurement ranges in IU/mL. Quantification covers a wide range through dilution. A newly developed quantitative reagent for HBsAg called Lumipulse HBsAg-HQ claims ten times the sensitivity of conventional reagents, and shows considerable potential for clinical settings. HBsAg levels vary in accordance with factors such as age, HBV DNA levels and HBV genotype.[66] HBV DNA is considered unsuitable for evaluating therapeutic effects because the HBV DNA levels often falls below the limit of detection shortly after the commencement of antiviral treatment. Several reports therefore recommend monitoring the HBsAg levels over time instead.

Some of the best evidence of the effects of resource competition

Some of the best evidence of the effects of resource competition on females comes from studies of the effects of increasing group size, which commonly depress fecundity and increase mortality of females and their offspring (Clutton-Brock, Albon & Guinness, 1982, van Schaik et al., 1983; Clutton-Brock, 2009b, 2009b, Silk, 2007a; Clutton-Brock, Hodge & Flower, 2008). Very similar patterns of resource competition occur in males, where breeding activity can also have high energetic

costs (Lane et al., 2010), and individuals compete both for direct access to resources Sunitinib and for access to feeding territories (Clutton-Brock, 2007), and survival is often sensitive to food shortages (Clutton-Brock, Major & Guinness, 1985). As well as competing for access to resources, females, like males, often compete to breed and, as in males, the structure of social groups intensifies conflicts of interest between group members (West-Eberhard, 1983, 1984). In some mammals, females compete to become sexually mature and, in extreme cases, one female suppresses the sexual development of all other females, evicting individuals that attempt BI 6727 clinical trial to breed (Creel & Creel, 2002; Clutton-Brock et al., 2006; Clutton-Brock, 2009b).

In others, females compete for access to mates, even though operational sex ratios (the ratio of males to females that are ready to mate at a given time) are biased towards males. For example, in some ungulates where males defend groups of females during a well-defined mating season, there is often more than one receptive female in a male’s harem on the same day, and females commonly compete for the attentions Progesterone of males (Bro-Jørgensen, 2002, 2011). Female competition may help females to ensure that they are mated by one or more males

within the time frame of their reproductive cycles (Parker & Ball, 2005), for the sperm supplies of successful males can become depleted (Dewsbury, 1982; Preston et al., 2001, Wedell, Gage & Parker 2002) or popular males may strategically conserve sperm for subsequent mating opportunities (Parker et al., 1996, Wedell et al., 2002). As would be expected, the frequency of overt female competition for mating partners increases in populations where adult sex ratios are strongly biased towards females (Milner-Gulland et al., 2003, Cheney, Silk & Seyfarth, 2012), where there is a high degree of reproductive synchrony (Emlen & Oring, 1977; Stockley & Bro-Jorgensen, 2011), or where females mate with multiple partners (Charlat et al., 2007).

001) We could not find any relationships between OLGA gastritis

001). We could not find any relationships between OLGA gastritis stage and sex, smoking as well as a familial history of gastric cancer. The severity of EGA significantly correlated with that of OLGA gastritis stage as presented in Table 2 Tamoxifen in vitro (Spearman correlation coefficient = 0.6, P < 0.001). All of the patients with high-stage OLGA gastritis had moderate-to-severe EGA (Fisher's exact test, P < 0.001). Using moderate-to-severe EGA as the diagnostic criterion for high-stage gastritis, the sensitivity, specificity, positive predictive value and negative predictive value were 100% (95% CI 75.3–100%),

57.7% (95% CI 51.5–63.7%), 10.3% (95% CI 5.6–17%), and 100% (95% CI 97.6–100%), respectively. There were 95 patients who were older than 40 years-of-age and had H. pylori infection in the present study (28 with mild EGA and 67 with moderate-to-severe EGA). In this subgroup of

patients, the positive predictive value increased to 19.4% (95% CI 10.8–30.9%). There were seven patients (2.5%) with low-grade CP-868596 in vitro dysplasia (3 in stage I, 3 in stage III and 1 in stage IV according to the OLGA gastritis system). All the dysplastic lesions were not endoscopically visible and were detected by systemic map biopsies according to the updated Sydney system. Dysplastic lesions were frequently detected in patients with high-stage gastritis: 4/13 (30.7%) patients with high-stage gastritis versus 3/267 (1.1%) patients with low-stage gastritis (i.e. stage 0–II; Fisher’s exact test P = 0.0001; OR = 39.1; 95% CI 6.1–270.8). Dysplastic lesions were also clustered in patients with moderate-to-severe EGA: 6/126 (4.76%) with moderate-to-severe EGA versus 1/154 (0.65%) with mild EGA (Fisher’s exact test P = 0.048; OR = 7.7; 95% CI 0.9–170.9). The southern area of Vietnam, where this study was carried out, Verteporfin has

a moderate incidence of gastric cancer. The age-standardized rate per 100 000 is 16.5 in males.16 The gastritis stage of patients in the present study who were under 40 years-of-age was almost between those in the low-risk and high-risk regions.7 Therefore, the result of the present study suggests that OLGA gastritis staging parallels the gastric cancer risk in our population. However, there was a difference between our result and those from other moderate-risk regions; we found a higher proportion of patients with gastritis stage I–II and no patients with high-stage gastritis, whereas Rugge et al. reported a lower proportion of patients with stage I–II, and a few patients with high-stage gastritis in Hong Kong and Taiwan. Gastric atrophy is more severe among patients with H. pylori infection and tends to increase when the infection is prolonged.17 The present study confirmed that high-stage gastritis is significantly associated with H. pylori infection and advanced age as reported in previous studies and in other populations.8,9 It has been reported that the atrophic progression is not invariable and only appeared in a subgroup of patients with H. pylori.

group Both groups showed marked thrombocytopenia Overall, IFN t

group. Both groups showed marked thrombocytopenia. Overall, IFN therapies tended

to be used more frequently in the Lap-sp. group compared with the PSE group. The operation time for Lap-sp. ranged 200–400 min (average, 237.7 ± 43.5 min). The blood loss ranged 10–1500 mL (average, 138.2 ± 190.6 mL). The mass of the spleen ranged 500–850 g (average, 346.3 ± 108.5 g). None of the patients experienced uncontrolled intraoperative bleeding. None of the patients required a conversion to open surgery. However, four out of 21 patients (19%) underwent hand-assisted laparoscopic surgery with an extension of the skin incision to 4 cm at the upper midline. There were no other major intraoperative complications. All of the patients in both groups tolerated the operations well. All PSE procedures were completed successfully with no intraoperative difficulty and no intraoperative complication. All patients tolerated the operations well. The actual Autophagy Compound Library clinical trial amount of devascularized parenchyma ranged 45–80% (average, 65.1%). Table 2 shows the post-intervention outcomes for both groups. The occurrence of continuing fever over 37°C and the use of anti-inflammatory analgesic drugs

were significantly lower in the Lap-sp. group than in the PSE group (P < 0.05). No major complication occurred in any patient in this study. Portal vein thrombosis occurred in two patients, pancreatic fistula in one patient and wound Decitabine manufacturer infection in one patient in the Lap-sp. group. However, these minor complications were successfully overcome using adequate treatments, including

Selleck Panobinostat administration of anticoagulation drugs, drainage and lavage. An intrasplenic abscess was found in one patient in the PSE group, which was successfully treated using puncture and drainage. There were no episodes of increased ascites or hepatic encephalopathy, which indicates severe liver dysfunction, in either group. The WBC count at 1 week after the interventions had increased significantly in both groups compared with the count prior to the interventions (Lap-sp. 5706 ± 1169 vs 2961 ± 1051/µL; PSE 4986 ± 1311 vs 3447 ± 1576/µL; both P < 0.05), and there was no statistically significant difference in the WBC count at 1 week after the interventions between the two groups. The average duration of hospital stay was shorter in the Lap-sp. group compared with the PSE group, although not statistically significantly. No cases of overwhelming post-splenectomy sepsis were observed in the Lap-sp. group throughout the duration of this study. Figure 1 shows the changes in platelet counts after each intervention. The platelet count 1 week after the interventions had increased significantly in both groups compared with the count prior to the interventions (Lap-sp. 22.0 ± 3.5 vs 6.2 ± 2.5 × 104/µL; PSE 12.9 ± 5.6 vs 5.2 ± 2.4 × 104/µL; both P < 0.05). The platelet count in the Lap-sp.

Although WNT proteins are predominantly associated with embryogen

Although WNT proteins are predominantly associated with embryogenesis, they are also important in disease progression. Previous studies described regulation of WNT-5A by the fibrogenic growth factor TGFβ. This interaction warrants further studies into the role of WNT-5A in liver fibrosis. Although gene-array studies identified increased WNT5 in fibrotic livers, the functional role of WNT-5A in this liver disease is not described yet. Therefore, our aim was to elucidate its role in liver

fibrosis. We studied the expression of WNT-5A in mouse and human livers in more detail and examined the relation between WNT-5A and various fibrosis-associated growth factors, cytokines and extracellular matrix proteins. WNT-5A and collagen I expression in normal and fibrotic mouse and human livers were analyzed with RT-PCR, ubiquitin-Proteasome pathway Western blot, and immuno-histochemistry.

The effects of cytokines/growth factors on WNT-5A and collagen I expression in LX2 cells were analyzed with RT-PCR and Western blot. The effects of WNT-5A on the expression of matrix proteins were determined after incubation of LX2 cells with WNT-5A siRNA in the absence and presence of TGFβ. WNT-5A gene and protein expression was significantly higher in fibrotic mouse and human livers compared to normal. Immunohistochemical analysis showed PD0325901 that WNT-5A expression was found in fibrotic collagen-rich areas of mouse and human livers. WNT-5A staining co-localized with desmin staining in these areas. In vitro studies with myofibroblasts showed that WNT-5A expression was significantly increased after incubation with TGF-β while PDGF-BB and pro-inflammatory cytokines (IL1β and TNFα) did not change WNT-5A expression. After silencing

of WNT-5A in myofibroblasts, using WNT-5A siRNA, reduced levels of collagen I, vimentin, and fibronectin in TGF-β-stimulated LX2 cells were found as compared to transfection controls. Interestingly, the antifibrotic cytokine IFNγ suppressed WNT-5A and collagen type I expressions in vitro. In addition, hepatic WNT-5A and collagen Ievels were significantly Urocanase reduced in CCL4 exposed (8 weeks) mice treated with (targeted) IFNγ as compared to untreated fibrotic mice. In conclusion, WNT-5A is significantly upregulated in fibrotic livers in particular in myofibroblasts in fibrotic bands. WNT-5A expression in myofibroblasts is induced by TGFβ and is involved in the regulation of various fibrotic matrix proteins. Targeted IFNγ therapy reduces hepatic WNT-5A expression and ameliorates liver fibrosis. These results identify WNT-5A as a potential new antifibrotic drug target.

The urease B subunit was recently shown to lead to Th17


The urease B subunit was recently shown to lead to Th17

responses in the mouse model of H. pylori infection [35]. When recombinant urease B was incubated directly with mouse splenic lymphocytes, IL-17-producing cells were increased, and when macrophages were incubated with recombinant urease B, IL-6 and IL-23 were produced to support Th17 development. H. pylori LPS has been shown to induce weaker immune responses than LPS from other bacteria. Particularly, LPS from H. pylori did not induce strong IL-1β, IL-6, or IL-8 responses [36] as other bacterial LPS does. H. pylori LPS was also shown click here to induce little NF-κB activation through TLR-4, but was shown in this study to induce IL-12 and IL-18 responses, which are thought to be pro-inflammatory. This is in contrast to another study that showed a lack of IL-12 and IL-2 induction by lymphocytes incubated with H. pylori LPS, which was accompanied by decreased cytotoxic PI3K inhibitor activity by lymphocytes incubated with H. pylori LPS compared to that of E. coli [37]. The beginning of 2011 was marked by a promising publication in the field of H. pylori vaccine development made by Moss et al. [38]. They used a computational method to predict novel T-cell epitopes. The multi-epitope vaccine was administered intranasally or intramuscularly to H. pylori-infected

mice, followed by a boost with the peptides themselves formulated in liposomes with CpG oligonucleotides and heat-labile enterotoxin. The vaccine induced a broad immune response, as determined Ponatinib mw by IFN-γ production, and led to a sterilizing immunity 32 weeks after challenge in 5 of 19 mice. Another promising vector platform for the

expression of H. pylori antigens was published in the beginning of 2011 by Iankov, et al. [39]. They produced a measles virus (MV) vaccine strain encoding the H. pylori neutrophil-activating protein (NAP). Nine months post vaccination, all animals immunized with MV strains expressing the secretory NAP antigen developed a strong humoral immunity against NAP within 2-4 weeks. By using IFN-γ ELISpot assay, they also confirmed effective NAP-specific cell-mediated immunity. Their experiments importantly demonstrated that immunization with a live replication competent vaccine expressing H. pylori molecules (NAP or potentially CagA, VacA, etc.) induced not only robust antibody production but also distinctive cell-mediated response against H. pylori antigens. Improved efficacy of vaccines may be achieved in new trials of vaccine formulations that include multiple antigens and use methods to optimize cellular immunity. An approach made by Chen et al. [40] used a H. pylori oipA gene-encoded construct co-delivered by IL-2 gene-encoded construct and B subunit heat-labile toxin of Escherichia coli gene-encoded construct.

In another experiment performed in WD-fed hApoE2 KI/PPAR-α KO mic

In another experiment performed in WD-fed hApoE2 KI/PPAR-α KO mice, the pure PPAR-γ agonist, rosiglitazone,

had no effect on inflammatory and fibrosis gene expression, whereas the pure PPAR-δ agonist, GW501516, showed a similar profile to GFT505 (Supporting Table 2). These results further suggest that, in hApoE2 KI/PPAR-α KO mice, GFT505 likely acts through activation of PPAR-δ in the liver. Olaparib To evaluate the effect of GFT505 on later stages of fatty liver disease, we next studied a model of advanced steatosis with strong inflammation induced by an MCD diet. In two independent experiments, insulin-resistant db/db mice were fed the MCD diet for 7 weeks and concomitantly treated with vehicle or 1, 3, 10 (experiment 1), or 30 mg/kg/day (experiment 2) of GFT505. The MCD diet provoked a significant increase of plasma ALT levels, associated with intrahepatic accumulation of cholesterol and TGs (Fig. 3A-C). Upon histological examination, a marked macrovesicular steatosis induced by MCD diet feeding was accompanied by increased buy Quizartinib inflammation and weak fibrosis (Fig. 4A-D). In mice concomitantly treated with GFT505, intrahepatic cholesterol and TG

content were significantly reduced in a dose-dependent manner to reach levels comparable to those in mice fed the control diet (Fig. 3B,C). Microscopic Immune system examination showed that GFT505 administration at 10 mg/kg/day completely prevented MCD diet-induced macrovesicular steatosis and inflammation (Fig. 4B,C). The weak hepatic fibrosis observed in

MCD diet-fed mice was not significantly reduced by GFT505 treatment (Fig. 4D). Consistent with liver protection by GFT505, plasma ALT activity was reduced to levels comparable to the control diet group (Fig. 3A), and liver weight was also significantly reduced (Fig. 3D). In a study performed at 30 mg/kg/day of GFT505 and giving similar results, transcriptomic analyses showed that the MCD diet-induced increased expression of hepatic inflammatory and profibrosis genes (IL-1β, TNF-α, TGF-β, and collagens) was blocked by GFT505 (Supporting Table 3). Moreover, hepatic expression of macrophage markers CD11b and F4/80 was significantly decreased by GFT505 treatment (Supporting Table 3). The effect of GFT505 on liver fibrosis was studied in a rat model induced by repeated IP injections of CCl4. Rats were injected with CCl4 or vehicle twice-weekly for 7 weeks, with parallel oral treatment with 30 mg/kg/day of GFT505 or vehicle. CCl4 administration induced a strong liver fibrosis with the formation of collagen bridges between veins (Fig. 5A), associated with an increased number of macrophages (KCs; Fig. 5B) and activated hepatic stellate cells (HSCs) expressing alpha smooth muscle actin (αSMA; Fig. 5C).

80 95% CI 4 31–405 1, P = 0 001) Among 14 patients who received

80 95% CI 4.31–405.1, P = 0.001). Among 14 patients who received operation initially, six (42%) patients had recurrence. One patient received radiofrequency

ablation; three (50%) patients received TAE combined with percutaneous ethanol injection (PEI) and one patient received chemotherapy due to lung metastasis and one patient received traditional herb therapy. Of the nine (75%) out of 12 patients who received percutaneous local ablation and had recurrence, six (66.6%) patients received TAE combined with PEI, one patient received TAE alone, one patient received PEI alone and one patient received BGB324 traditional herb therapy. Of the 34 (77%) out of 44 patients who received TAE and had recurrence, 20 patients received TAE, seven (20%) patients received TAE combined with PEI, five patients received percutaneous local ablation therapy and two patients received radiation therapy. In the current, large-scale study, a total of 61 318 adults aged 40 years or more were screened for HCC, and 97 cases were detected. This prevalence of HCC (158/105) is three to five times higher than the reported annual incidence in Taiwan, and may be associated with an earlier detection of more asymptomatic or subclinical HCC cases. More than half of the cases (n = 51, 52.6%) detected were in the very early or early stage of HCC, and thus

were detected early enough to have a chance of treatment being effective. As based on the practice guidelines of the American Association for the Study of Liver Disease (AASLD), cases of either very early or early stage HCC should receive

curative treatment, cases of intermediate stage click here be treated with transcatheter arterial chemoembolization, and cases beyond the intermediate stage should DNA Methyltransferas inhibitor undergo either experimental or conservative treatment.26 In the current study, 70 of the 88 treatable cases (79.5%) received heterogeneous treatment in one of nine hospitals with various facilities because a national consensus or practice guidelines do not exist, the selection of treatment modalities varied from doctor to doctor. In addition, 18 treatable cases resisted our suggestions and chose either alternative medicine or no active treatment, which suggests that post-screening education and consultation services should be augmented. In order to demonstrate the survival benefit in the screening cases, a randomized controlled study provided the best evidence. However, ethical problems are a major concern in carrying out this kind of study. According to the randomized controlled study of Zhang et al.,11 3-year and 4-year survival rates were 7.2% and 0% in the control group who did not receive the screening program. In the current study, 3-year and 4-year overall survival rate was 56.8% and 46.8%, respectively, in patients that received community screening, which was higher than the historical control.

In the secondary analysis

In the secondary analysis

Kinase Inhibitor Library supplier increased levels of genera Parabacteroides and Collinsella were observed comparing PSC-UC with UC samples. Conclusions: This is the first study, to our knowledge, to characterise the intestinal microbiota of patients with UC with and without PSC. The genus level analysis revealed differences comparing PSC-UC and UC subjects which may reflect microbial representatives of PSC pathogenesis. Increased levels of genus Collinsella observed in primary and secondary analyses are of interest due to the role of these organisms in bile acid metabolism. Functional annotations of the genus level findings and replication in independent panels are presently ongoing. Disclosures: David Kevans – Speaking and Teaching: Abbvie The following people have nothing to disclose: Andrea D. Tyler, Kristian Holm, Kristin K. Jørgensen, Morten H. Vatn, Tom H. Karlsen, Dirk Gevers, Johannes R. Hov, Mark S. Silverberg Background/aims: Vascular adhesion protein (VAP)−1 is an adhesion molecule which possesses potent amine oxidase activity, and deaminates dietary amines resulting in the production of H2O2.Through this function, VAP-1 leads to activation of NFқB in hepatic sinusoidal endothelium (HSEC) resulting in expression of mucosal-vascular cell-adhesion

molecule-1 (MAdCAM-1); a mechanism proposed to contribute to the homing of gut-tropic lymphocytes expressing α4β7 to the liver. Given the putative role this pathway has in hepatic diseases complicating inflammatory bowel disease PLX3397 cost (IBD), we set out to quantify circulating/soluble (sVAP-1) and intrahepatic VAP-1 enzyme activity in primary sclerosing cholangitis (PSC), and evaluate the functional consequence of its inhibition on MAdCAM-1 dependent lymphocyte recruitment to HSEC. Methods: Total VAP-1 concentration was measured by ELISA. VAP-1 amine oxidase activity was

quantified in human serum and explanted liver tissue using the amplex red assay. Flow-based adhesion assays were performed using human HSEC isolated from almost liver explants, activated with TNFα and methylamine (VAP-1 substrate), and treated with VAP-1 antibody or semicarbazide (VAP-1 enzyme inhibitor). FAC-sorted peripheral blood leucocytes expressing α4β7 were perfused over HSEC under flow rates simulating physiological shear (0.05Pa) and adhesion and transmigration quantified. Results: Patients with PSC had significantly higher circulating median VAP-1 enzyme activity (114.5pmol H2〇 2 produced/min/ml serum, IQR 100.6-134.7) than patients with IBD (60.3, IQR 38.5-73.0; P=0.006), normal controls (84.0, IQR 77.7-105.7; P=0.020) and individuals with PBC (53.9, IQR 33.0-90.9; P=0.006), and trended higher than AIH (77.6, IQR 51.0-124.5; P=0.200) (Mann-Whitney). Total sVAP-1 concentration correlated well with sVAP-1 enzyme activity (R2=0.75). Intrahepatic median VAP-1 activity was also significantly higher in PSC (97.