Pathogenesis of Helicobacter Pylori Infection: Colonization, Virulence Factors of the Bacterium and Immune and Non-immune Host Response

Helicobacter pylori (Hp), a gram-negative, spiral-shaped bacterium is one of the most widely spread pathogens in humans, as it concerns half of the world population. Mechanisms that allow Hp to cause a life-long infection involve modulation of the immune response and host cellular processes which include activation of the innate immune response, resistance to phagocytosis, modulation of dendritic cell activity and regulatory T cells, and production of proinflammatory cytokines. This is accomplished via virulence factors such as colonization factors (a variety of adhesins), factors that allow it to evade host defence (flagella and motility, urease system, induction of hypochlorhydria) and factors that are responsible for tissue injury (heat shock proteins A and B, vacuolating cytotoxin A, neutrophil activating protein of Hp, and cytotoxin-associated gene A). The interaction between bacterial effectors, environmental factors (genetic susceptibility to infection) and factors that modulate the host's response, such as polymorphisms in genes encoding cytokines or cytokine receptors, have been shown to influence the clinical outcome of Hp infection either towards peptic ulcer and/or cancer. Future studies, directed toward understanding interactions between Hp and immune cells in vivo, may lead to the development of novel therapeutic approaches for eradication of Hp

A multicentre study of nutrition risk assessment in adult patients with inflammatory bowel disease attending outpatient clinics

Background: Overnutrition and undernutrition can affect patients with inflammatory bowel disease (IBD). Although all IBD outpatients should be screened for nutrition risk, screening is not routinely performed, potentially leading to reduced identification and treatment. This study aimed to estimate the prevalence of nutrition risk in adult IBD outpatients and the proportion of cases who discussed diet and/or nutrition during their routine clinical appointment. Methods: Adults with IBD attending outpatient clinics at four hospitals in Greece and in UK were recruited. Demographic and anthropometric data were collected using face-to-face patient interviews and clinical records. Patients were classified as high (i.e. BMI <18.5kg/m2 or 18.5-54 20kg/m2 and weight loss >5%), moderate (i.e. BMI 20-25 kg/m2 and weight loss >5%) or low risk of undernutrition and high risk of obesity (i.e. BMI 25-30% and weight gain >5%). The proportion of patients who discussed diet and/or nutrition during their clinical appointment was calculated. Results: In total, 390 IBD patients participated. Sixteen (4%) patients were underweight, 113 (29%) were overweight and 71 (18%) were obese. Twenty-one (5%) patients were at high risk of undernutrition; of these four (19%) were under dietetic care. Of those at high risk of undernutrition, 11 (52%) had discussed diet and/or nutrition during their routine clinical appointment. Fifty-six (14%) patients had gained more than 5% weight since their last recorded/reported weight and 19 (5%) were at high risk of obesity. Conclusions: Few patients were identified to be at high risk of undernutrition and less than a fifth of these were under dietetic care. Overnutrition is a growing problem in IBD with almost half of adult patients being overweight or obese. Diet and/or nutrition were not routinely discussed in this group of IBD outpatients

Factors Associated With Short- and Long-Term Outcomes of Therapy for Crohn’s Disease

Background & AimsOur post hoc analysis assessed the association of early (at weeks 26–30) clinical, endoscopic, biologic, and pharmacokinetic outcomes with corticosteroid-free remission at week 50 (CSFR50); CSFR50 was observed in 55.2% and 65.4% of patients treated with infliximab, alone or in combination with azathioprine, respectively.MethodsWe analyzed data from 203 patients: 96 received infliximab monotherapy and 107 received combination therapy. Receiver operating characteristic analysis was used to set cut-off points for the week 30 trough serum infliximab concentration (SIC30) and percentage change, from baseline, in the C-reactive protein (CRP) level at week 26, to predict CSFR50. Univariate and multivariate procedures analyzed predictive parameters of CSFR50 (odds ratio [OR] and 95% confidence interval [CI]). Mucosal healing (MH, zero ulcers) and CRP normalization (<8.0 mg/L) also were assessed.ResultsTrough SIC30 was higher in patients with than without CSFR50. Patients given combination therapy had higher trough SIC30s than those given monotherapy. Median trough SIC30 was significantly higher in patients with than without CSFR50 among those on infliximab monotherapy (2.14 vs 0.80 μg/mL; P = .006), but not for those on combination therapy (3.56 vs 3.54 μg/mL; P=.31). In patients with increased baseline levels of CRP (n = 120), corticosteroid-free remission at week 26 (CSFR26) (OR, 4.09; 95% CI, 1.65–10.11), and trough SIC30s of 3.0 μg/mL or greater (OR, 3.20; 95% CI, 1.38–7.42) were associated significantly with CSFR50. In patients evaluable for MH (n = 123), trough SIC30s of 3.0 μg/mL or greater (OR, 3.34; 95% CI, 1.53–7.28) and CRP normalization (OR, 2.69; 95% CI, 1.10–6.54) were associated significantly with MH at week 26 (MH26). Furthermore, CSFR26 (OR, 4.43; 95% CI, 1.81–10.82) and MH26 (OR, 3.01; 95% CI, 1.33–6.81) were associated significantly with CSFR50.ConclusionsTrough SIC30 is associated positively with MH26; CSFR26 and MH26 are independent predictors of CSFR50. Trough SIC30 of 3.0 μg/mL or greater early during maintenance treatment is an important determinant of clinical and endoscopic Crohn’s disease outcomes. ClinicalTrials.gov number, NCT00094458

A Lyophilized Form of Saccharomyces Boulardii Enhances the Helicobacter pylori Eradication Rates of Omeprazole-Triple Therapy in Patients With Peptic Ulcer Disease or Functional Dyspepsia

Background: Saccharomyces boulardii prevents antibiotic-induced diarrhea and exerts anti-H.pylori effects in vitro and in vivo. Aim: To assess whether S. boulardii enhances the efficacy of classic triple therapy in eradicating H. pylori. Methods: Seventy patients with peptic ulcer or functional dyspepsia according to Rome III criteria and H. pylori infection were treated with omeprazole 20 mg bid, clarithromycin 500 mg bid and amoxicillin 1 g bid for 14 days. A total of 36 out of 70 (51%) patients were randomized to S. boulardii [Ultralevure®, two capsules tid for 14 days (group A) and 34 (49%) on no intervention (group B). H. pylori eradication was assessed by a 13C-Urea Breath Test. Results: At baseline there were no significant differences between the two groups in any patient or disease characteristics. H. pylori was eradicated in 30/36 (83.4%) patients in group A vs 20/34 (58.8%) in group B (P=0.034, 95% CI 4.4% to 43.6%). Seven patients in group B (20.6%) and 1 patient in group A stopped treatment because of diarrhea (95% CI 3.3% to 32.7%, P=0.026). Multi-factorial analysis did not reveal any patient or disease related parameter linked to treatment outcome except for the use of the probiotic. Conclusion: S. boulardii enhanced the effect of classic triple therapy mainly by preventing antibiotic- and/or proton pump inhibitor-induced diarrhea

The management of iron deficiency in inflammatory bowel disease

__Background__ Iron deficiency is a common and undertreated problem in inflammatory bowel disease (IBD). __Aim__ To develop an online tool to support treatment choice at the patient-specific level. __Methods__ Using the RAND/UCLA Appropriateness Method (RUAM), a European expert panel assessed the appropriateness of treatment regimens for a variety of clinical scenarios in patients with non-anaemic iron deficiency (NAID) and iron deficiency anaemia (IDA). Treatment options included adjustment of IBD medication only, oral iron supplementation, high-/low-dose intravenous (IV) regimens, IV iron plus erythropoietin-stimulating agent (ESA), and blood transfusion. The panel process consisted of two individual rating rounds and three plenary discussion meetings. __Results__ The panel reached agreement on 71% of treatment indications. 'No treatment' was never considered appropriate, and repeat treatment after previous failure was generally discouraged. For 98% of scenarios, at least one treatment was appropriate. Adjustment of IBD medication was deemed appropriate in all patients with active disease. Use of oral iron was mainly considered an option in NAID and mildly anaemic patients without disease activity. IV regimens were often judged appropriate, with high-dose IV iron being the preferred option in 77% of IDA scenarios. Blood transfusion and IV+ESA were indicated in exceptional cases only. __Conclusions__ The RUAM revealed high agreement amongst experts on the management of iron deficiency in patients with IBD. High-dose IV iron was more often considered appropriate than other options. To facilitate dissemination of the recommendations, panel outcomes were embedded in an online tool, accessible via http://ferroscope.com/

ECCO Position statement on the use of biosimilars for inflammatory bowel disease – An update

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Celiac Disease in Adult Patients: Specific Autoantibodies in the Diagnosis, Monitoring, and Screening

The increasing prevalence of celiac disease (CD), especially in adults, its atypical clinical presentation, and the strict, lifelong adherence to gluten-free diet (GFD) as the only option for healthy state create an imperative need for noninvasive methods that can effectively diagnose CD and monitor GFD. Aim. Evaluation of anti-endomysium (EmA) and anti-tissue transglutaminase IgA (tTG-A) antibodies in CD diagnosis, GFD monitoring, and first degree relatives screening in CD adult patients. Methods. 70 newly diagnosed Greek adult patients, 70 controls, and 47 first degree relatives were tested for the presence of EmA and tTG-A. The CD patients were monitored during a 3-year period. Results. EmA predictive ability for CD diagnosis was slightly better compared to tTG-A (P=0.043). EmA could assess compliance with GFD already from the beginning of the diet, while both EmA and tTG-A had an equal ability to discriminate between strictly and partially compliant patients after the first semester and so on. Screening of first degree relatives resulted in the identification of 2 undiagnosed CD cases. Conclusions. Both EmA and tTG-A are suitable markers in the CD diagnosis, in the screening of CD among first degree relatives, having also an equal performance in the long term monitoring