Yirga Falcone

A mechanistic multicentre, parallel group, randomised placebo-controlled trial of mesalazine for the treatment of IBS with diarrhoea (IBS-D)

Introduction Immune activation has been reported in the mucosa of IBS patients with diarrhoea (IBS-D), and some small studies have suggested that mesalazine may reduce symptoms. We performed a double-blind, randomised placebo-controlled trial of 2 g mesalazine twice daily versus placebo for 3 months in patients with Rome III criteria IBS-D. Primary outcome was daily average stool frequency during weeks 11–12; secondary outcomes were abdominal pain, stool consistency, urgency and satisfactory relief of IBS symptoms. Methods Participants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of ‘satisfactory relief of IBS symptoms’. Results 136 patients with IBS-D (82 women, 54 men) were randomised, 10 patients withdrew from each group. Analysis by intention to treat showed the daily average stool frequency during weeks 11 and 12 were mean (SD), 2.8 (1.2) in mesalazine and 2.7 (1.9) in the placebo group with no significant group difference, (95% CI) 0.1 (−0.33 to 0.53), p=0.66. Mesalazine did not improve abdominal pain, stool consistency nor percentage with satisfactory relief compared with placebo during the last two-weeks follow-up. Conclusions This study does not support any clinically meaningful benefit or harm of mesalazine compared with placebo in unselected patients with IBS-D. More precise subtyping based on underlying disease mechanisms is needed to allow more effective targeting of treatment in IBS. Trial registration number NCT01316718.

A mechanistic multi-centre, parallel group, randomised placebo controlled trial of Mesalazine for treatment of irritable bowel syndrome with diarrhoea (IBS-D)

Introduction Immune activation has been reported in the mucosa of IBS patients with diarrhoea (IBS-D), and some small studies have suggested that mesalazine may reduce symptoms. We performed a double-blind, randomised placebo-controlled trial of 2 g mesalazine twice daily versus placebo for 3 months in patients with Rome III criteria IBS-D. Primary outcome was daily average stool frequency during weeks 11–12; secondary outcomes were abdominal pain, stool consistency, urgency and satisfactory relief of IBS symptoms. Methods Participants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of ‘satisfactory relief of IBS symptoms’. Results 136 patients with IBS-D (82 women, 54 men) were randomised, 10 patients withdrew from each group. Analysis by intention to treat showed the daily average stool frequency during weeks 11 and 12 were mean (SD), 2.8 (1.2) in mesalazine and 2.7 (1.9) in the placebo group with no significant group difference, (95% CI) 0.1 (−0.33 to 0.53), p=0.66. Mesalazine did not improve abdominal pain, stool consistency nor percentage with satisfactory relief compared with placebo during the last two-weeks follow-up. Conclusions This study does not support any clinically meaningful benefit or harm of mesalazine compared with placebo in unselected patients with IBS-D. More precise subtyping based on underlying disease mechanisms is needed to allow more effective targeting of treatment in IBS. Trial registration number NCT01316718.

PTU-047 High prevalence of clostridium difficile ribotype 078 in IBD outpatients

Background and Objectives Point prevalence studies have reported higher carriage rates of C. difficile in IBD patients compared with the general population, but longitudinal prospective data are lacking. The objectives of this observational study were to investigate and molecularly characterise isolates of C. difficile, collected prospectively on a monthly basis over a one-year period among IBD outpatients and healthy controls (HC). Methods At enrolment, recruited participants had established diagnoses of UC (n=16) and Crohn’s disease (n=6) and reported no recent hospitalisation or exposure to antibiotics. PCR ribotype and toxin status (cytotoxigenic culture) were determined for all +ive stool cultures. All participants underwent a monthly telephone interview to identify potential risk factors for C. difficile acquisition (changes in medications, exposure to antibiotics, clinic attendances, hospitalisation) and to assess for disease activity (Harvey-Bradshaw Index and Simple Clinical Activity Colitis Index). Results Two patients underwent physician-initiated laboratory testing of C. difficile during the sample collection phase, although no participants developed or were treated for C. difficile infection. C. difficile was cultured from 29/223 samples (13%) representing 16/22 patients and 1 of 5 HC with concurrent antibiotic exposure in 6/29 visits (20%). Of the toxin +ive isolates (n=25; 078, 005, 302 and 015), 72% (n=21) were PCR ribotype 078. Toxigenic negative ribotypes included 023, 026 and 656. Of those toxin +ive isolates, 9 samples (36%) were associated with relapsing IBD of which 7/9 were ribotype 078. Multiple stool specimens also tested +ive for different ribotypes in 3 patients with UC, all of whom were taking regular immunosuppressants. WGS studies of the 078 isolates revealed marked genetic similarity, with only 3 of the 21 isolates varying by 1 or more nucleotides when compared to the 078 reference genome, suggesting there may have been a common source for cross-transmission. Conclusions The high prevalence of PCR ribotype 078 in this IBD outpatient cohort is consistent with the recent emergence of this strain in the community. These results reinforce the importance of testing all in-and outpatients with an apparent flare or relapsing IBD for carriage of toxigenic C. difficile to inform optimal management strategies. Future research is needed to understand the predominance of 078 isolates in IBD, particularly in the context of clinical relapse.

OC-019 Iron Deficiency Anaemia and Hepcidin Levels in H. Pylori Infected Patients

Introduction IDA affects up to 5% of the adult population in the developing world. There is an association between H. pylori (Hp) infection and incidence of unexplained IDA, but the mechanisms remain unclear. In children it has been suggested that Hp disturbs the iron regulatory mechanism via hepicidin. This peptide hormone induces internalisation and degradation of the iron transporter protein ferroportin thus limiting iron absorption and release. Hepcidin expression is induced by inflammation, but how this relates to Hp and IDA has not been fully elucidated, particularly in adults. This pilot study aimed to characterise local and systemic iron transporter expression in IDA patients with and without Hp infection, in comparison to Hp negative dyspepsia controls. Methods Patients undergoing routine endoscopy for IDA (HpIDA and IDA groups, n = 18 and 40 respectively) or without IDA (control group, n = 18) donated blood and biopsy samples with informed consent and ethical approval. Hp status was assessed by three biopsy based tests and by serology. Duodenal and gastric biopsies were evaluated by immunohistochemistry for ferroportin and hepcidin, in addition to H&E staining for inflammation and atrophy grading. All scoring was carried out by experienced blinded histopathologists. A commercial ELISA assay was used to quantify serum Hepcidin-25. Results As expected, anaemia parameters were significantly lower in the HpIDA and IDA groups compared to the controls (P < 0.0001). Surprisingly, serum hepcidin concentrations were significantly reduced in the HpIDA and IDA groups compared to the controls (9 fold, P = 0.009 and 5 fold, P < 0.0001 respectively). Hp infection was associated with gastric expression of hepcidin, particularly in the corpus when compared to controls. This corresponded with the cytoplasmic relocalisation of ferroportin (n = 12; 67%) in the duodenal enterocytes of patients with HpIDA compared to controls, where the ferroportin was actively expressed. Hepcidin was also found to be expressed in the duodenum of both controls and HpIDA. Significant atrophy was observed in both IDA groups. Conclusion IDA was associated with significantly lower levels of serum hepcidin in contrast to previous studies. Local or systemic factors such as inflammatory mediators could be driving this response as more severe atrophy was observed in both IDA groups. We now aim to perform quantitative analysis of hepcidin in the gastric specimens using RT-qPCR to further evaluate whether local Hp transcriptionally upregulated hepcidin expression might cause these effects on iron transport. Disclosure of Interest None Declared

PTU-257 Correlation of adipokines and intestinal inflammation with mesenteric adipose tissue volumes in symptomatic and asymptomatic diverticulosis

Introduction Colonic diverticulosis affects up to 66% of those > 65 years in the UK. Obesity is a risk factor for developing symptomatic diverticular disease (DD) including abscess formation and perforation. These inflammatory complications may relate to the known pro-inflammatory secretions (adipokines and cytokines) of visceral adipose tissue (VAT). This study looks at correlations between abdominal adipose tissue and adipokines and symptoms in DD by comparing asymptomatic (ASYMP) and symptomatic patients (SYMPDD). Method 55 patients, BMI 20.5–39.5 kg m-2comprising 17 ASYMP and 38 SYMPDD with chronic abdominal pain (29 with somatization score (PHQ12-SS) ≥7 and 9 <7). All were scanned with a 1.5T MRI scanner after an overnight fast. Blood and stool samples were collected and concentrations of adiponectin, leptin and faecal calprotectin were determined. Results SYMPDD patients had more fat, leptin and calprotectin than ASYMP but these differences were not significant (Table 1). However overall (n = 55) adiponectin was found to correlate negatively with VAT (r = -0.344, p = 0.01), abdominal volume (r = -0.510, p = 0.0002), and BMI (r = -0.425, p = 0.002). Leptin in contrast correlated strongly with SAT (r = 0.762, p < 0.0001) and TAT (r = 0.698, p < 0.0001), while the correlation with VAT was weaker (r = 0.384, p = 0.004). Stool calprotectin correlated negatively with adiponectin (r = -0.353, p = 0.009) and weakly with stool frequency in SYMPDD patients but this was not significant (Spearman r = 0.3, P = 0.057). Stool form correlated positively with BMI (Spearman r = 0.4, P = 0.005). SS were significantly higher in SYMPDD versus ASYMP patients (P < 0.001). Conclusion MR imaging demonstrates that VAT, SAT and TAT correlated with both adipokine concentrations and faecal calprotectin in DD patients. The study confirms the known link between leptin, adiponectin and obesity, and shows that abdominal VAT is related to intestinal inflammation. Whether this link is primary or secondary due to differences in diet or microbiota or both remains to be established. Disclosure of interest None Declared.Abstract PTU-257 Table 1 Asymptomatic Symptomatic PHQ12SS ≥7 Symptomatic PHQ12SS <7 n 17 29 9 PHQ12 SS 5 ± 5 11 ± 4 5 ± 1 Days of pain 0 8.8 ± 4.0 6.5 ± 5.3 BMI (kgm-2) 28.3 ± 4.9 28.5 ± 4.7 29 ± 4.5 VAT (mL) 1050 ± 634 1014 ± 581 1306 ± 1014 Stool frequency (stools/day) 2.1 ± 1.5 2.0 ± 1.1 1.7 ± 1.0 Calprotectin (ug mL-1) 56.9 ± 43.2 89.4 ± 71.5 60.5 ± 86.0 Adiponectin (µg ml-1) 4.5 ± 2.4 5.0 ± 2.8 4.4 ± 2.6 Leptin (ng mL-1) 15.3 ± 13.8 18.8 ± 15.1 24.8 ± 19.2