Disclosures: The following people have nothing to disclose: Colleen Flanigan, Rachel Hart-Malloy Background & aims: Hepatitis A (HAV) and hepatitis B (HBV) vaccinations in patients with chronic liver disease are accepted as standard MAPK Inhibitor Library in vivo of care and several professional societies have recently proposed vaccination rates as a quantifiable measure of quality of care. We determined HAV and HBV vaccination recommendation rates

in a tertiary care referral hepatology clinic and the impact of electronic health record (EHR)-based reminders on adherence to vaccination guidelines. Methods: We reviewed the records of 705 patients with chronic liver disease referred to our liver clinic in 2008 with at least two follow-up visits during the subsequent year. Demographics, referral source, etiology, and hepatitis serology were recorded. We determined whether eligible patients were offered vaccination and whether patients received vaccination. Barriers to vaccination were determined by a follow-up telephone interview. We obtained prior approval from the University of Pittsburgh selleck products Medical Center Quality Improvement Committee for this study. Results: In patients with chronic liver disease, HAV and HBV serologic testing

was performed in just 14.5% and 17.7%, respectively, prior to their referral to the liver clinic,. After evaluation in the liver clinic, the overall rates of HAV and HBV testing increased to 76.7% and 74%, respectively. Hepatologists recommended HAV vaccination in 63% and HBV vaccination in 59.7% of eligible patients. Patient demographics or disease etiology did not influence recommendation rates. Significant variability was observed in vaccination recommendation rates amongst individual providers (30–98.6%) within the same practice and no correlation was found with patient volume. A computer-based vaccination reminder for Medicare patients with

hepatitis C infection failed to increase vaccination recommendation rates in that cohort. Most patients that were offered vaccination but failed to get them, gave no specific reason for their noncompliance other than lack of awareness regarding the importance of vaccinations. Insurance coverage was a barrier to vaccination Paclitaxel in only a minority of patients. Conclusions: Hepatitis vaccination rates in patients with chronic liver disease are very low in the community and suboptimal even in an academic, sub-speciality clinic. There is wide-variability in provider adherence to vaccination guidelines and does not correlate with patient volume. As adherence to vaccination guidelines is adopted as a quality metric for gastroenterologists, further research is urgently needed to understand and overcome barriers to hepatitis vaccinations in patients with chronic liver disease.

1D) (migration index, NECA + HGF: 1.45 ± 0.13; 8-PST + NECA + HGF: 2.67 ± 0.3; P < 0.05). Adenosine signals through four receptor subtypes: A1, A2a, A2b, and A3. Adenosine subtype–specific antagonists were used to determine the role of receptor subtypes (DPCPX [10 nM], A1; ZM241385 [1 μM], A2a;

MRS-1706 [10 nM], A2b; and MRS-1523 (5 μM], A3). The ability of adenosine to inhibit MSC chemotaxis to HGF was significantly blocked by the A2a receptor subtype antagonist but not by the A1, A2b, and A3 receptor-selective antagonists (Fig. 1D) (migration index, NECA + HGF: 1.45 ± 0.13; Zm241385 + NECA + HGF: 3.6 ± 0.3; selleck compound P < 0.05). This demonstrates that the A2a receptor subtype is responsible for the inhibition of HGF-induced MSC chemotaxis. Signaling downstream of the A2a receptor is mediated predominantly via adenylate cyclase activation, resulting in elevation in cAMP.20 We found a central role for cAMP downstream of signaling of A2aR in MSCs. The adenosine agonist NECA increased cAMP levels, and this effect was blocked by the A2a receptor antagonist (Fig. 2A). Forskolin, which induces elevations in cAMP independent of adenosine receptor activation, mimics the inhibitory effect of NECA on HGF-induced MSC chemotaxis (Fig. 2B) (migration index, HGF: 2.02 Gefitinib chemical structure ± 0.15; forskolin + HGF 1.08 ± 0.05, P < 0.05). Cyclic AMP mediates downstream

effects through activation of protein kinase A (PKA) in many cells.21 We tested the ability of the PKA inhibitor ST-HT31 Ribonucleotide reductase to reverse forskolin-inhibited chemotaxis and found that forskolin-induced inhibition of MSC migration was antagonized by the PKA inhibitor ST-HT31 (Fig. 2B) (migration index, forskolin + HGF: 1.08 ± 0.05, ST-HT31+ forskolin + HGF: 2.25

± 0.38; P < 0.05). We further found that the PKA inhibitor could block the effect of NECA on HGF-induced MSC chemotaxis (Fig. 2C) (migration index, NECA+ HGF: 1.53 ± 0.19, ST-HT31 + NECA + HGF: 4.2 ± 0.69; P < 0.05). These findings demonstrate that adenosine inhibits HGF-induced MSC chemotaxis through a cAMP/PKA-dependent pathway. To elucidate the intracellular signaling pathways responsible for adenosine and HGF interaction, we investigated pathways responsible for HGF-induced chemotaxis in MSCs. HGF signaling via c-met is known to increase cytosolic Ca++ and lead to activation of Rac1.22 To determine whether Rac1 inhibition may be a mechanism by which adenosine inhibits HGF-induced chemotaxis, we tested the ability of a Rac 1 inhibitor (NSC23766) and a Rho kinase inhibitor (Y27632) to inhibit HGF-induced chemotaxis. The Rho kinase inhibitor had no significant effect on HGF-induced migration (Fig. 3A). However, the Rac1 inhibitor significantly blocked HGF-induced MSC migration (Fig. 3A). These findings support a requirement for Rac1 in HGF-induced MSC chemotaxis (migration index, HGF: 2.0 ± 0.2; Rac1 inhibitor + HGF: 1.2 ± 1.2; P < 0.05).

In these cases, whole exome or whole genome sequencing may be beneficial, although at present, the costs associated with performing this routinely in a diagnostic laboratory and the extensive downstream bioinformatic analysis required may be prohibitive. “
“Background and Aims:  Proton pump inhibitors (PPI) have been

rarely used for prevention of upper gastrointestinal bleeding (UGIB) induced by non-steroidal anti-inflammatory drugs (NSAIDs) and/or aspirin in Japan. The increased incidence of UGIB in the aged society is becoming a serious problem. The aim of this study was to retrospectively evaluate whether PPI can prevent UGIB. Methods:  We examined records of 2367 patients (aged 67.9 ± 15.1 years, male 1271) attending the only hospital serving the rural area, with little population movement. We investigated the correlation between the www.selleckchem.com/products/Gefitinib.html frequency of usage of medicine (PPI, NVP-AUY922 histamine 2 receptor antagonists [H2RA], NSAIDs, aspirin) and incidence of UGIB over 12 years. UGIB was defined as cases with hematemesis and/or melena and definite bleeding at upper gastrointestinal endoscopy. The annual incidence of UGIB of inhabitants (16 065 ± 375.3 persons/year) was evaluated. The frequency of usage of medicine

was compared with the total number of patients prescribed any medication (1080 ± 33.2 persons/year). Results:  The frequency of PPI usage has increased significantly 4.6%30.8% (P < 0.05). NSAIDs and aspirin usage increased significantly in the latter half of the survey period (P < 0.05). The annual incidence of UGIB significantly decreased 160.8 23.6/100 000 inhabitants

per annum (P ≤ 0.05) due to widespread use of PPI. No patients died due to UGIB after 2006. The incidence of UGIB and the prevalence of PPI usage were found to have a negative correlation (r = −0.804, P = 0.0016). Conclusions:  By widespread use of PPI, UGIB and related death has declined significantly. This survey showed that continuous PPI treatment decreases UGIB and related death in community medicine. “
“Viral infections are often linked to altered drug metabolism in patients; however, the underlying molecular mechanisms remain Bacterial neuraminidase unclear. Here we describe a mechanism by which activation of antiviral responses by the synthetic double-stranded RNA ligand, polyinosinic-polycytidylic acid (polyI:C), leads to decreased acetaminophen (APAP) metabolism and hepatotoxicity. PolyI:C administration down-regulates expression of retinoic X receptor-α (RXRα) as well as its heterodimeric partner pregnane X receptor (PXR) in mice. This down-regulation results in suppression of downstream cytochrome P450 enzymes involved in conversion of APAP to its toxic metabolite. Although the effects of polyI:C on drug metabolism are often attributed to interferon production, we report that polyI:C can decrease APAP metabolism in the absence of the type I interferon receptor.

28 The major strengths

of the present study are as follows: (1) its population, which includes both males and females; (2) its careful and homogeneous acquisition of the anthropometric parameter of interest; and (3) most importantly, its long follow-up period (15 years). Its limitations are as follows: (1) its lack of intermediate data points for the parameters of interest during the 15-year observation period; (2) its lack of data about dietary habits and habitual physical activity, which have a well-recognized impact on insulin sensitivity RGFP966 manufacturer and a fatty liver; and (3) the inferiority of the homeostasis model assessment versus the glucose clamp technique, which is the gold CDK and cancer standard for the assessment of insulin sensitivity. Nevertheless, it has been suggested that the homeostasis model assessment is specifically suited for large-scale epidemiological studies when only fasting glucose and insulin concentrations are available.23 In conclusion, FLI as a surrogate marker of NAFLD is associated with hepatic-related, CVD, and cancer mortality rates regardless of the diabetic status, fasting glucose concentration, or metabolic syndrome. This provides epidemiological support for the hypothesis that NAFLD is an important and independent factor affecting not only the hepatic prognosis but also the nonhepatic prognosis

of affected people. The tight association of FLI with HOMA-IR makes it difficult for us at this stage to understand the primacy of NAFLD versus systemic insulin resistance in explaining the strong Adenylyl cyclase association of fatty livers with all-cause mortality. “
“Immunosuppression

(IS) withdrawal from calcineurin inhibitors is only possible in ∼20% of liver transplant recipients. However, mammalian target of rapamycin inhibitors (e.g., sirolimus; SRL) appear to be more immunoregulatory and might promote a tolerant state for withdrawal. Our aim was to determine whether systemic (i.e., blood, marrow, and allograft) signatures of immunoregulation are promoted by conversion from tacrolimus (TAC) to SRL. We therefore performed the following serial assays before and after SRL conversion in liver transplant recipients to test for enhanced markers of immunoregulation: (1) flow-cytometry immunophenotyping of peripheral blood mononuclear cells (PBMCs) and bone marrow aspirates for regulatory T cells (Tregs) (e.g., CD4+CD25+++FOXP3+) and regulatory dendritic cells (DCregs) (immunoglobulin-like transcript 3+/4+); (2) liver biopsy immunohistochemical staining (e.g., FOXP3:CD3 and CD4:CD8 ratios) and immunophenotyping of biopsy-derived Tregs after growth in culture; (3) effects of pre- versus postconversion sera on Treg generation in mixed lymphocyte reactions; (4) peripheral blood nonspecific CD4 responses; and (5) peripheral blood gene transcripts and proteomic profiles.

28 The major strengths

of the present study are as follows: (1) its population, which includes both males and females; (2) its careful and homogeneous acquisition of the anthropometric parameter of interest; and (3) most importantly, its long follow-up period (15 years). Its limitations are as follows: (1) its lack of intermediate data points for the parameters of interest during the 15-year observation period; (2) its lack of data about dietary habits and habitual physical activity, which have a well-recognized impact on insulin sensitivity buy Tanespimycin and a fatty liver; and (3) the inferiority of the homeostasis model assessment versus the glucose clamp technique, which is the gold Ku-0059436 ic50 standard for the assessment of insulin sensitivity. Nevertheless, it has been suggested that the homeostasis model assessment is specifically suited for large-scale epidemiological studies when only fasting glucose and insulin concentrations are available.23 In conclusion, FLI as a surrogate marker of NAFLD is associated with hepatic-related, CVD, and cancer mortality rates regardless of the diabetic status, fasting glucose concentration, or metabolic syndrome. This provides epidemiological support for the hypothesis that NAFLD is an important and independent factor affecting not only the hepatic prognosis but also the nonhepatic prognosis

of affected people. The tight association of FLI with HOMA-IR makes it difficult for us at this stage to understand the primacy of NAFLD versus systemic insulin resistance in explaining the strong cAMP association of fatty livers with all-cause mortality. “
“Immunosuppression

(IS) withdrawal from calcineurin inhibitors is only possible in ∼20% of liver transplant recipients. However, mammalian target of rapamycin inhibitors (e.g., sirolimus; SRL) appear to be more immunoregulatory and might promote a tolerant state for withdrawal. Our aim was to determine whether systemic (i.e., blood, marrow, and allograft) signatures of immunoregulation are promoted by conversion from tacrolimus (TAC) to SRL. We therefore performed the following serial assays before and after SRL conversion in liver transplant recipients to test for enhanced markers of immunoregulation: (1) flow-cytometry immunophenotyping of peripheral blood mononuclear cells (PBMCs) and bone marrow aspirates for regulatory T cells (Tregs) (e.g., CD4+CD25+++FOXP3+) and regulatory dendritic cells (DCregs) (immunoglobulin-like transcript 3+/4+); (2) liver biopsy immunohistochemical staining (e.g., FOXP3:CD3 and CD4:CD8 ratios) and immunophenotyping of biopsy-derived Tregs after growth in culture; (3) effects of pre- versus postconversion sera on Treg generation in mixed lymphocyte reactions; (4) peripheral blood nonspecific CD4 responses; and (5) peripheral blood gene transcripts and proteomic profiles.

Pettersson score was higher in mono-infected than in the other two groups (P < 0.001) (Fig. 1) and was also found to be higher in all pts treated with secondary prophylaxis than in pts treated on demand, without any difference in the three groups. The F BMD and L BMD were reduced in all three groups (Table 2). There were no statistically significant differences

between the three groups Dorsomorphin molecular weight on the measured BMD at the F DXA. The measured BMD values at the L DXA were significantly lower in the co-infected group (all values <−1) than in the other two groups (normal values) (P < 0.05). The b-ALP level was higher in co-infected (P < 0.001) and mono-infected (P < 0.001) than in uninfected pts (Fig. 2). The NTx levels were also higher in co-infected (P < 0.01) and mono-infected (P < 0.02) than in uninfected pts (Fig. 3). To investigate if statistically significant correlations exist between different groups and all the collected data, we performed a multivariate regression analysis. Because the sample size was insufficient to investigate differences in results between the three groups, Ruxolitinib cost we redefine the group classes by means of the

following binary schemes: Infected/Uninfected HIV positive/HIV negative The results of multivariate binomial regression analysis for the aforementioned groups as dependent variables and clinical, radiological and laboratory data as independent variables are reported in Table 4. Analysis (a) shows that the presence

of viral infection is significantly correlated to an increased b-ALP (P < 0.002) whereas analysis (b) shows an increase of NTx in HIV positive pts Fossariinae (P < 0.05). The WFH and radiological scores result is significantly correlated to the HIV infection (P < 0.05 and P < 0.006 respectively). We also evaluated which measured data represent risk factors for osteoporosis. To this end we performed multivariate binomial regression analysis for osteoporotic/non-osteoporotic pts as dependent variable and clinical and laboratory data as independent variables (analysis c): WFH score (P < 0.001) results as significant predictor of low BMD; our analysis suggests a possible role for 25-OH Vit D level (P < 0.08). Osteoporosis has been recently recognized as an important co-morbidity in haemophilia. The pathogenesis of reduced BMD in adult pts with haemophilia is most likely multi-factorial and the presence of HIV and/or HCV infections may play an important role. High prevalence of hypovitaminosis D has been reported in haemophilia [12]; similar data have already been reported in HIV populations [19, 20, 21, 22 and 23]. In our cohort a high prevalence of hypovitaminosis D was confirmed, independently from the presence of infections (Table 3). The low vitamin D level was not related to an impaired renal function (with a consequent decrease of alpha-1-hydroxylase), as shown by the creatinine and creatinine clearance normal values.

ER stress–associated steatosis and steatohepatitis has been one of the most extensively studied consequences of ER stress response. The ER plays an important part in fatty acid synthesis and cholesterol metabolism. The relationship between ER stress and fatty liver is a bilateral one. Steatosis has been shown to promote ER stress; conversely, ER stress response leads to steatosis (Fig. 3). Despite many uncertainties, current evidence strongly

supports an important role for ER stress response in nonalcoholic fatty liver disease (NAFLD). Multiple mechanisms for ER stress–induced steatosis have been proposed: (1) ER stress induces TRB3 via ATF4 and CHOP. TRB3 inhibits the activity of Akt, an insulin-sensitizing kinase which mediates insulin signaling in hepatocytes.

Interestingly, TRB3 expression Alvelestat mouse is increased in the liver of diabetic mice, and knockdown of hepatic TRB3 expression leads to improved glucose tolerance.26, 27 (2) ER stress response activates JNK-mediated inhibition of insulin NVP-AUY922 chemical structure receptor substrate-1 (IRS-1), leading to insulin resistance which can promote hepatic steatosis; insulin resistance due to TRB3 and JNK leads to hyperinsulinemia and increased hepatic lipogenesis; (3) Phosphorylation of eIF2α results in induction of c/EBP proteins and increased expression of genes that regulate lipogenesis (peroxisome proliferator-activated receptor γ)28; (4) When hepatocytes are stressed, PERK-mediated shutdown of protein synthesis can lead to decreased Insig-1 protein, a negative regulator of lipid synthesis which retains sterol regulatory element binding protein (SREBP)–SREBP cleavage activating protein (SCAP) complex in the ER. Insig-1 protein has a very short half-life and falls rapidly upon ER stress response–induced translational arrest; the subsequent translocation of SREBPs to the Golgi leads to cleavage and Morin Hydrate enhanced lipogenesis29, 30; (5) PERK-mediated global protein translational arrest along with increased ERAD mediated by IRE1/JNK can result in decreased apolipoprotein B (apoB) levels promoting steatosis31; and (6) GRP78 may directly interact with

SREBP so that displacement of GRP78 may allow SREBPs to translocate to the Golgi and undergo RIP.32 Thus, a combination of enhanced lipogenesis via SREBP activation (including insulin resistance) and impaired very low density lipoprotein secretion via decreased apoB contribute to ER stress–induced fatty liver. A variety of supportive evidence suggests that prolonged UPR/ER stress response leads to steatosis: SREBPs are a family of ER resident proteins which function as transcription factors in the control of fatty acid, TG, and cholesterol synthesis.33, 34 They are synthesized as inactive precursors bound to the ER in a complex with SCAP. Once released from Insig, SREBPs are escorted to the Golgi by SCAP where they undergo RIP and promote lipogenesis.

T2-weighted STN contrast did not show appreciable changes with age for both the groups (Spearman correlation ≈ −.1). STN, a common stimulation target, shows an age dependent trend for normalized FSTIR MRI contrast. Although larger patient pools are needed, our work points to tissue relaxation-based changes in STN that may provide insight in early stages of brain pathology involving DBS targets in medically refractory Parkinson’s disease. “
“We performed a longitudinal analysis based on magnetic resonance (MR) imaging to investigate the brain structural and perfusion changes caused by insulin therapy in patients with type II diabetes. High resolution DZNeP solubility dmso three-dimensional T1-weighted fast spoiled gradient

recalled echo images and flow-sensitive alternating inversion recovery (FAIR) images were obtained from 11 patients

with type II diabetes before and 1 year after initiation of insulin therapy and 11 normal controls. Brain volume changes were investigated by a longitudinal voxel-based morphometry (VBM), and perfusion changes were evaluated by FAIR imaging between baseline and follow-up data. Significant regional gray matter (GM) expansion located in bilateral frontal, parietal, and left occipital lobes, and regional white matter (WM) expansion was shown in left precentral subcortical WM and right angular subcortical selleck WM after insulin therapy (P < .05 with FDR correction). Brain hyperperfusion was detected in bilateral frontal cortex, left occipital cortex, and right temporal cortex after insulin therapy (P < .05). In patients with type II diabetes, brain expansion and hyperperfusion were demonstrated 1 year after initiation of insulin therapy, and insulin therapy could contribute to the brain volume gainment in the patients with type II diabetes.

“
“We assess the feasibility of using the newly designed suboccipital probe fixation device (SPFD) as a convenient and reliable tool for simultaneous measurement of vasomotor reactivity (VMR) in the middle cerebral artery (MCA) Sitaxentan and basilar artery (BA). We analyzed 30 healthy volunteers’ VMR values by using both SPFD and conventional handheld method. The VMR values were measured as percentage increase of the mean flow velocity on transcranial Doppler (TCD) in response to hypercapnia induced by the rebreathing method. The VMR tests were performed three times: (1) for both MCAs, (2) for the index MCA (the better signal window) and the BA by using the SPFD, and (3) for the index MCA and the BA by using the handheld technique. The VMR values of the right and left MCAs were similar (P > .05). Although the VMR values of the index MCA and the BA obtained by SPFD application and the handheld technique were similar (P > .05), the correlation coefficient of VMR values obtained by using the SPFD was higher (r= .827, P < .001 vs. r= .568, P= .001).

40; intermediate differentiation, n = 15, AFC = 3.25; P = 0.0081). Finally, we determined a possible association of ABC expression with tumor size. Up-regulation of ABCB6 and ABCC2 was significantly higher in patients with tumors <30 mm than in patients with tumors >31 mm (<30 mm, n = 4; >31 mm, n = 15), with AFC

values of respectively 4.6 and 2.3 for ABCB6 (P = 0.0144) and 4.2 and 1.5 for ABCC2 (P = 0.0022). MI-503 nmr We hypothesized that ABC gene expression might be regulated by cellular miRNAs, i.e., ABC genes up-regulation in HCC would be the consequence of the down-regulation of cellular miRNAs. In order to obtain miRNA expression signatures, RNA was isolated from 10 HCC and three HL samples. To minimize variation in the miRNA profile, only 10 HCC with alcohol etiology were selected from the 19 available (FR01, FR03, FR05, FR06, FR07, FR08, FR10, FR11, FR14, and FR18). miRNA expression was determined by Taqman 384-well microfluidic array including 378 cellular miRNAs and six control wells and data find more were normalized to mammalian

U6 RNA. In total, 361 out of 378 miRNAs were detectable. Changes in miRNA expression between 2-and 40-fold were considered up-regulation and changes between 0- and 0.5-fold were considered down-regulation. Average miRNA expression was compared in HCC and HL groups by two-tailed t test. miRNA expression in HCC compared with HL control was significantly higher for 11 cellular miRNAs and lower for 79 miRNAs, which accounted for respectively 3% and 22% of the detectable miRNAs (Fig. 2; Fig. S2). Analysis of the conservation of the 90 dysregulated miRNAs revealed that 87 were conserved up to the mouse, and 25 up to the chicken (Table S6). Next a subset of miRNAs quantified with the microfluidic array was cross-examined on all samples: 19 paired HCC and AHL, and three HL. Six miRNAs were selected: miR-135b, miR-145, miR-199a-3p/a/b, and miR-296 because they were consistently down-regulated in the 10 HCC patient samples (low standard deviation). Expression of these six miRNAs was quantified using single miRNA Taqman assays (Fig. 3). First, miRNA expression

in HL from pancreatic Dimethyl sulfoxide cancer patients and AHL from liver cancer patients was similar (Fig. 3). This indicated that the miRNA profile is not affected in HL tissues despite the different background of these samples. Second, differences in miRNA expression observed between paired AHL and HCC samples were significant for miR-145, miR-199a-3p, miR-199a-5p, and miR-199b, hence confirming the miRNA signature in HCC from the microfluidic array. These differences were also significant for miR-135b when the two patients presenting the highest variation in each group are excluded (Fig. 3; miR-135b; FR01; FR12, FR13, and FR19; P = 0.0070). miR-296 presented a down-regulated profile but the differences were not statistically significant.

1, p<0.0005). In terms of extreme symptom load, 27% of <50 year old patients with poor QoL had between 8 and 10 (the maximum possible) significant symptom domain scores compared with 16% of the over 60s with poor QoL. In contrast to symptom load, UDCA non-response did not predict poor QoL in either age

group (>60 years: CS 2.4, OR 1.68 (0.9-3.2), p=0.12; <50 years: CS 1.1, OR 1.3 (0.7-2.1), p=0.3). Social dysfunction symptoms were a particularly discriminating feature in young patients with poor QoL compared to Trichostatin A clinical trial good QoL (OR for association between QoL status and social symptom status 423 [95% CI 58-3078], p<0.0001). Amongst younger patients with poor QoL, social dysfunction symptoms correlated find more particularly strongly with depression, fatigue and cognitive symptoms (r=0.67, 0.56, and 0.8 respectively, all p<0.0001). Discussion The UK-PBC Study has shown that there are marked phenotypic differences in PBC patients presenting at a younger age with worse perceived QoL and significantly increased symptom burden. Social

dysfunction symptoms are a specific feature of younger patients and associate strongly with depression, fatigue and cognitive symptoms. Offering psychological support and targeting specific symptoms in young PBC patients offer a potential approach to life quality improvement. Disclosures: Richard N. Sandford – Advisory Committees or Review Panels: Otsuka; Grant/ Research Support: Intercept David Jones – Consulting: Intercept The following people have nothing to disclose: Jessica K. Dyson, Laura Griffiths, Samantha J. Ducker, George F. Mells Background: The pathophysiology of PSC remains unclear, but a close association with IBD is overt. We sought to document changes in the gut microbiota in PSC and IBD by characterising gut adherent bacteria in patients with PSC and IBD, IBD alone and healthy controls. Methods: We collected pan-co-lonic biopsy samples from 9 controls, 10 IBD and 11 PSC-IBD patients, undergoing colonoscopy. Gut microbiota

were characterised using 16s rRNA based analysis of the V3 – V4 region (Illumina MiSeq). The sequences were clustered into operational taxonomic units using Uparse and analysed using Qiime and Nitroxoline the Vegan package in R. Results: We identified little difference in richness and complexity (Simpson’s index) of the microbiota between conditions. However an analysis of variance showed a significant difference in the composition of the microbiota between conditions, irrespective of biopsy site (p = 0.001). This was confirmed by constrained ordination, which resulted in clear separation between the three groups (Fig 1). However there was no difference in microbiota between sites. Indeed sites from the same patient were highly similar and clustered together. PSC-IBD and IBD showed reduced levels of Prevotella and Roseburia (a butyrate producer).