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Abstract: Oral budesonide is a second‐generation steroid that allows local, selective treatment of the gastrointestinal tract and the liver, minimizing systemic exposure. The results of randomized trials comparing budesonide versus placebo or active comparators have led to expert recommendations that budesonide be used to treat mild or moderate active ileocecal Crohn's disease, microscopic colitis (including both collagenous and lymphocytic colitis), ulcerative colitis, and non‐cirrhotic autoimmune hepatitis. The mechanism of budesonide action obviates the need for dose tapering due to safety reasons after induction therapy. Where low‐dose budesonide is used to maintain remission, usually in microscopic colitis, it does not appear to have adverse safety implications other than slight reductions in cortisol levels on rare occasions. As a gut‐selective and liver‐selective corticosteroid, budesonide offers an appealing alternative to conventional systemic glucocorticoids in diseases of these organs. [ABSTRACT FROM AUTHOR]

Background Liver injury during inflammatory bowel disease (IBD) is primarily diagnosed by liver biopsy, which has a small but serious risk of severe complications. The aim of this study was to assess liver stiffness, and subsequently the prevalence and associations of liver fibrosis in IBD patients with thiopurine therapy and other clinical factors, by using transient elastography (TE). Methods In this prospective, international two-center study, included IBD-patients underwent TE measurements. Laboratory results and medication reports, radiology results and historical liver biopsy results were extracted from the patient charts. Results Transient elastography results of 168 patients were presented. Moderate and severe fibrosis were detected in 4% (7/168) and 1% (1/168) of the cohort, respectively. Factors contributing to lower liver stiffness were female gender and (historical) exposure to azathioprine. Further, there was a statistical trend towards lower liver stiffness in patients using thiopurines overall (4.7 vs. 5.2 kPa, p = 0.07). Liver stiffness correlated positively with waist circumference, liver enzyme tests, hemoglobin and 6-methylmercaptopurine concentration and negatively with platelet count. Conclusion Exposure to thiopurine therapy was not associated with higher liver stiffness, although no clinical difference in severity of fibrosis was detected. Further research should robustly determine the accuracy of TE as an evaluation of liver fibrosis in IBD patients. [ABSTRACT FROM AUTHOR]

Crohn''s disease and ulcerative colitis are chronic idiopathic inflammatory disorders of the gastro-intestinal tract. Although the exact etiology of these inflammatory bowel diseases (IBD) remains elusive, both immunological and genetic determinants have been identified that are involved in disease pathogenesis. Murine models of mucosal inflammation have provided a detailed insight into the immunological processes underlying chronic mucosal inflammation. Here, we highlight some recent findings that have contributed to our understanding of human IBD. [Copyright &y& Elsevier]

The inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis, are chronic inflammatory disorders of the gastrointestinal tract. Enormous progress has been made recently in understanding the pathogenesis of these diseases. Through the study of patients and mouse models, it has emerged that Crohn's disease is driven by the production of interleukin-12 (IL-12) and interferon-? (IFN-?), whereas ulcerative colitis is probably driven by the production of IL-13. A second area of progress is in the identification of specific genetic abnormalities that are responsible for disease. The most important finding is the identification of mutations in the gene that encodes NOD2 (nucleotide-binding oligomerization domain 2) protein in a subgroup of patients with Crohn's disease. Here, we discuss these recent findings and the implications for therapy. [ABSTRACT FROM AUTHOR]

Studies the allele frequencies of the codon 10 and the codon 25 transforming growth factor-β (TGFB) gene polymorphism in a Dutch population of inflammatory bowel disease (IBD) patients. Importance of TGF-&beta in maintaining intestinal immune homeostasis; Likelihood of the anti-inflammatory and immunosuppressive effects of TGF-&beta1 to offer important potential physiological and therapeutic applications; Irrelevance of the codon 10 and codon 15 TGFB1 gene polymorphism in defining the susceptibility to and the nature of the clinical course of IBD.

Background & Aims: Exacerbations of ulcerative colitis (UC) are dominated by massive neutrophil influx in the lamina propria with concomitant mucosal ulceration. The prevalent antibody in this area is immunoglobulin A (IgA). Interestingly, the IgA Fc receptor (FcαRI) potently activates neutrophils. As such, we investigated whether IgA-FcαRI interaction contributes to tissue damage in UC. Methods: Response of neutrophils to bovine serum albumin–, IgG-, or IgA-coated beads and Escherichia coli was investigated with 3-dimensional culture systems, real-time video microscopy, and (fluorescence) microscopy. In vivo studies were performed using human FcαRI transgenic mice or nontransgenic littermates. Microscopic slides of UC patients were stained for IgA, FcαRI, and neutrophils. Results: In vitro and in vivo cross-linking of FcαRI on neutrophils by serum IgA or uptake of IgA-coated E coli led to neutrophil migration. The responsible chemotactic factor was identified as leukotriene B4. Moreover, dimeric IgA (dIgA), which is produced in the lamina propria, but neither secretory IgA nor IgG, was equally capable of inducing neutrophil recruitment. We furthermore showed that FcαRI+-neutrophils in the colon of UC patients had phagocytosed IgA-antigen complexes. Conclusions: Neutrophils are the first cells that arrive at inflammatory sites once pathogens have crossed the epithelial barrier. FcαRI-dIgA interactions therefore may constitute an essential activation step to recruit more neutrophils, hereby eradicating impending infections. However, excessive IgA-antigen complexes can sustain a perpetuating inflammatory loop in UC, hereby seriously aggravating morbidity. Novel therapeutic strategies that block dIgA-FcαRI interactions, and therefore diminish neutrophil migration and activation, may dampen the uncontrolled inflammatory processes in these patients. [Copyright &y& Elsevier]

Background & Aims: Non-invasive biomarkers are gaining interest for monitoring disease activity in patients with inflammatory bowel diseases (IBD). Fecal calprotectin is a reliable biomarker but patients often report the collection of feces being unpleasant and cumbersome. In this study, we aimed to assess if salivary calprotectin could be used as a non-invasive biomarker to determine disease activity instead of fecal calprotectin. Methods: In this cross-sectional explorative cohort study, stimulated saliva was collected from patients with an established IBD diagnosis and healthy controls. The concentration of calprotectin in saliva was determined by a particle-enhanced turbidimetric immunoassay. Intestinal disease activity was assessed with fecal calprotectin levels and the Harvey-Bradshaw Index (HBI) or Simple Clinical Colitis Activity Index (SCCAI). Missing data were handled using multiple imputation. Results: Sixty-three patients (41 Crohn's disease and 22 ulcerative colitis) and 11 controls were included. Patients had a mean fecal calprotectin of 138.78 µg/g and a median salivary calprotectin of 1.87 mg/L. No significant correlation was found between salivary calprotectin and fecal calprotectin levels (p=0.495). When patients were stratified in two subgroups based on a fecal calprotectin cut-off value of 250 µg/g, there were no significant differences in salivary calprotectin levels between both patient groups (p=0.641) and between patients and healthy controls (p=0.248). Also, salivary, and fecal calprotectin levels were not significantly different when stratifying patients in two subgroups, active disease and remission, using HBI/SCCAI scores. Conclusions: Salivary calprotectin does not correlate to fecal calprotectin and disease activity scores in patients, making it unreliable for assessing IBD activity. [ABSTRACT FROM AUTHOR]

Background & Aims: In most cases celiac disease (CD) is successfully treated with a gluten-free diet (GFD). However, some patients become refractory to the GFD. Refractory CD (RCD) patients have an increased risk for developing enteropathy associated T-cell lymphoma and early diagnosis is therefore of importance. Currently, RCD diagnosis relies on endoscopy and adequate serological markers are lacking. Antibodies against glycoprotein-2 (GP2A) were described in Crohn's disease (CrD) and active CD but not in ulcerative colitis (UC), suggesting this is a specific marker for small intestinal lesions. Methods: Sera obtained from patients visiting our outpatient clinic for routine serological tests for diagnosis and/or follow-up of inflammatory bowel disease (n=78), active CD (n=45), GFD (n=34) and RCD (n=15) were analysed for GP2A titres. Results: Increased GP2A-IgA levels in CrD and active CD as compared to controls (p<0.001) and lack thereof in UC was confirmed. However, we could not confirm the association with small bowel localization within the CrD patient group. Within CD patients, we demonstrated a significant decrease of GP2A-IgA titres upon a GFD and increased levels in RCD patients as compared to patients on a GFD. Although GP2A-IgA was not associated with the degree of villous atrophy, GP2A-IgA levels were able to distinguish RCD patients from GFD patients (ROC AUC=0.79, p=0.002). Conclusion: Follow-up of GP2A-IgA titres in CD patients on a GFD may help to identify patients at risk for developing RCD. [ABSTRACT FROM AUTHOR]

IL-23R gene variants have been identified as risk factors for two major inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis, but how they contribute to disease is poorly understood. In this study, we show that the rs10889677 variant in the 3′-untranslated region of the IL-23R gene displays enhanced levels of both mRNA and protein production of IL-23R. This can be attributed to a loss of binding capacity for the microRNAs (miRNAs) Let-7e and Let-7f by the variant allele. Indeed, inhibition and overexpression of these miRNAs influenced the expression of the wild type but not the variant allele. Our data clearly demonstrate a role for miRNA-mediated dysregulation of IL-23R signaling, correlated with a single nucleotide polymorphism in the IL-23R strongly associated with IBD susceptibility. This implies that this mutation, in combination with other genetic risk factors, can lead to disease through sustained IL-23R signaling, contributing to the chronicity of IBD. [ABSTRACT FROM AUTHOR]