Mohammed Nabil Quraishi

The gut microbiota and host health: a new clinical frontier

Over the last 10–15u2005years, our understanding of the composition and functions of the human gut microbiota has increased exponentially. To a large extent, this has been due to new ‘omic’ technologies that have facilitated large-scale analysis of the genetic and metabolic profile of this microbial community, revealing it to be comparable in influence to a new organ in the body and offering the possibility of a new route for therapeutic intervention. Moreover, it might be more accurate to think of it like an immune system: a collection of cells that work in unison with the host and that can promote health but sometimes initiate disease. This review gives an update on the current knowledge in the area of gut disorders, in particular metabolic syndrome and obesity-related disease, liver disease, IBD and colorectal cancer. The potential of manipulating the gut microbiota in these disorders is assessed, with an examination of the latest and most relevant evidence relating to antibiotics, probiotics, prebiotics, polyphenols and faecal microbiota transplantation.

National survey of practice of faecal microbiota transplantation for Clostridium difficile infection in the UK

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Long term outcomes of initial infliximab therapy for inflammatory pouch pathology: a multi-Centre retrospective study

Abstract Background: Restorative proctocolectomy with ileal pouch-anal anastomosis is considered the procedure of choice in patients with ulcerative colitis refractory to medical therapy. Subsequent inflammation of the pouch is a common complication and in some cases, pouchitis fails to respond to antibiotics, the mainstay of treatment. In such cases, corticosteroids, immunomodulatory or biologic treatments are options. However, our understanding of the efficacy of anti-tumour necrosis factor medications in both chronic pouchitis and Crohn’s-like inflammation is based on studies that include relatively small numbers of patients. Methods: This was an observational, retrospective, multi-centre study to assess the long-term effectiveness and safety of infliximab (IFX) for inflammatory disorders related to the ileoanal pouch. The primary outcome was the development of IFX failure defined by early failure to IFX or secondary loss of response to IFX. Results: Thirty-four patients met the inclusion criteria; 18/34 (53%) who were initiated on IFX for inflammatory disorders of the pouch had IFX failure, 3/34 (8%) had early failure and 15/34 (44%) had secondary loss of response with a median follow-up of 280 days (range 3–47 months). In total, 24/34 (71%) avoided an ileostomy by switching to other medical therapies at a median follow-up of 366 days (1–130 months). Conclusions: Initial IFX therapy for pouch inflammatory conditions is associated with IFX failure in just over half of all patients. Despite a high failure rate, an ileostomy can be avoided in almost three-quarters of patients at four years by using other medical therapies.

The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines

Citation for published version (Harvard): Mullish, B, Quraishi, MN, Segal, J, McCune, V, Baxter, M, Marsden, GL, Moore, D, Colville, A, Bhala, N, Iqbal, TH, Settle, C, Kontkowski, G, Hart, AL, Hawkey, P, Goldenberg, SD & Williams, HRT 2018, The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines, Gut. https://doi.org/10.1016/j.jhin.2018.07.037

The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

Interest in the therapeutic potential of faecal microbiota transplant (FMT) has been increasing globally in recent years, particularly as a result of randomised studies in which it has been used as an intervention. The main focus of these studies has been the treatment of recurrent or refractory Clostridium difficile infection (CDI), but there is also an emerging evidence base regarding potential applications in non-CDI settings. The key clinical stakeholders for the provision and governance of FMT services in the UK have tended to be in two major specialty areas: gastroenterology and microbiology/infectious diseases. While the National Institute for Health and Care Excellence (NICE) guidance (2014) for use of FMT for recurrent or refractory CDI has become accepted in the UK, clear evidence-based UK guidelines for FMT have been lacking. This resulted in discussions between the British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS), and a joint BSG/HIS FMT working group was established. This guideline document is the culmination of that joint dialogue.

The Paddington International Virtual Chromoendoscopy Score in ulcerative colitis exhibits very good inter-rater agreement after computerized module training: a multicenter study across academic and community practice (with video)

BACKGROUND AND AIMSnElectronic virtual chromoendoscopy (EVC) can demonstrate ongoing disease activity in ulcerative colitis (UC), even when Mayo subscores suggest healing. However, applicability of EVC technology outside the expert setting has yet to be determined.nnnMETHODSnFifteen participants across 5 centers reviewed a computerized training module outlining high-definition and EVC (iScan) colonoscopy modes. Interobserver agreement was then tested (Mayo score, Ulcerative Colitis Endoscopic Index of Severity [UCEIS], and the Paddington International Virtual Chromoendoscopy Score [PICaSSO] for UC), using a colonoscopy video library (30 cases reviewed pretraining and 30 post-training). Knowledge sustainability was retested in a second round (42 cases; 9/15 participants), 6 months after training provision.nnnRESULTSnPretraining intraclass correlation coefficients (ICC) were good for the Mayo endoscopic subscore (ICC, .775), UCEIS scoring erosions/ulcers (ICC, .770), and UCEIS overall (ICC, .786) and for mucosal (ICC, .754) and vascular components of PICaSSO (ICC, .622). For the vascular components of UCEIS, agreement was only moderate (ICC, .429) and did not enhance post-training (ICC, .417); conversely, use of PICaSSO improved post-training (mucosal ICC, .848; vascular, .746). Histologic correlation using the New York Mt. Sinai System was strong for both PICaSSO components (Spearmans ρ for mucosal: .925; vascular, .873; Pxa0< .001 for both). Moreover, accuracy in specifically discriminating quiescent from mild histologic strata was strongest for PICaSSO (area under the receiver operating characteristic curve [AUROC] for mucosal, .781; vascular, .715) compared with Mayo (AUROC, .708) and UCEIS (AUROC for UCEIS overall, .705; vascular, .562; bleeding, .645; erosions/ulcers, .696). Inter-rater reliability for PICaSSO was sustained by round 2 participants (round 1 and 2 ICC for mucosal, .873 and .869, respectively; vascular, .715 and .783, respectively), together with histologic correlation (ρ mucosal, .934; vascular, .938; Pxa0< .001 for both).nnnCONCLUSIONSnPICaSSO demonstrates good interobserver agreement across all levels of experience, providing excellent correlation with histology. Given the ability to discriminate subtle endoscopic features, PICaSSO may be applied to refine stratified treatment paradigms for UC patients.

PWE-048 The virtual electronic chromoendoscopy score in ulcerative colitis exhibits very good inter-rater agreement in scoring mucosal and vascular changes after computerised module training: a study across academic and community practice

Introduction Mucosal healing is the desired therapeutic endpoint for clinical trials in ulcerative colitis (UC). However, conventional white light endoscopy may fall short of capturing the full spectrum of inflammatory change; and virtual electronic chromoendoscopy (VEC) can show ongoing disease activity even when Mayo scores suggest healing (Iacucci et al. Endoscopy 2015 and 2017). Applicability of VEC scoring requires determination outside the expert setting; thus, our aim was to provide external validation among trainees, consultant gastroenterologists and colorectal surgeons, practicing across six general and specialist centres. Method 15 participants reviewed a computerised training module outlining HD and i-Scan modes. Anchor points for the VEC score indicated mucosal changes (crypt distortion, 0 [A–C]; microerosions, I [1–3]; erosions, II [1–3]; and ulceration, III [1–3]) and vascular alterations (non-dilated vessels, 0 [A–C]; dilated/crowded vessels, I [1–3]; mucosal bleeding, II [1–3]; and intraluminal bleeding, III [1–3]). Performance accuracy was tested using a video library pre-/post-training (n=30). Agreement between raters was tested for the Mayo score, UCEIS and VEC score, and results correlated with histology (New York Mount Sinai system). Results The inter-rater agreement was very good for the Mayo score, UCEIS scoring erosions/ulcers and overall, and for VEC scoring mucosal patterns in both modules (Table 1). For the vascular components of UCEIS agreement was only moderate, and did not improve post-training; unlike the agreement for VEC vascular patterns which improved significantly to very good. Correlation between histology and VEC score was highly significant for mucosal and vascular scoring (Spearman’s ρ: 0.910, p<0.001; and 0.907, p<0.001; respectively, Figure 1). This was superior to the Mayo score (0.876, p<0.001) and UCEIS (0.887, p<0.001). Conclusion The VEC score demonstrates very good inter-observer agreement across all levels of experience and provides excellent correlation with histology. Unlike UCEIS, the VEC score does not have subjective elements (e.g. mucosal erythema, incidental/contact friability) and may better delineate vascular changes due to filter technology. Given the ability to define subtle endoscopic features, VEC may be applied to further stratify treatment paradigms for patients with UC. Disclosure of Interest P. Trivedi Conflict with: Received funding from the National Institute for Health Research (NIHR), Conflict with: This article presents independent research funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health, S Ghosh: None Declared, M Iacucci: None Declared Abstract PWE-048 Table 1 Abstract PWE-048 Figure 1

OC-040 National Survey of Practice of Faecal Microbiota Transplantation for Clostridium Difficile Infection in the United Kingdom

Introduction The National Institute of Health and Care Excellence recommend the use of faecal microbiota transplantation (FMT) for recurrent or refractory Clostridium difficile infection (CDI), as studies have shown it to be a highly effective therapy with a primary cure rate of over 90%.1 We aimed to conduct a National survey to explore current practice of FMT and the challenges faced by hospitals in setting up this novel treatment strategy. Methods UK gastroenterologists, microbiologists and infectious disease physicians were invited to take part in a National survey by completing an online questionnaire over a five month period from October 2015. Results A total of 255 responses were obtained, of which 219 were evaluable. These came from 124 microbiologists/infectious disease clinicians and 95 gastroenterologists. The survey covered 130 independent sites: 112 acute NHS Trusts in England, 9 hospitals in Scotland and 9 hospitals in Wales. Only 28% (36/130) had performed FMT for refractory or recurrent CDI, of which 58% (21/36) of sites had experience of performing FMT for over 1 year, but only 19% (7/36) had treated at least 10 patients. 67% (24/36) made FMT on site while 33% (12/36) obtained FMT from elsewhere to administer at their hospital. Apart from one site that used FMT for refractory ulcerative colitis there were no other indications for its use. Of the 94 independent sites that did not perform FMT for refractory or recurrent CDI, 45% (42/94) believed that they were unable to do it due to lack of facilities, 38% (36/94) did not know where to start, however only 5% (5/94) felt reluctant to do it because of its perceived unpleasantness. Of those sites not performing the procedure, 70% (66/94) suggested that they would be keen to have support in setting up an FMT service for CDI locally. Only 29% (27/94) of the sites that did not perform FMT had referred their patients elsewhere; primarily to Glasgow, Birmingham and Exeter. Conclusion In the largest National survey done to date exploring the practice of FMT in UK, we have shown that only a quarter of responding sites performed FMT for recurrent or refractory CDI. There are significant challenges faced by hospitals in setting up this service. However, most welcomed support due to unfamiliarity with the perceived logistical hurdles. A central quality controlled and regulated FMT preparation, delivery and support service for the UK may be an efficient model to ensure continued and safe access to this novel treatment strategy for patients in the NHS. Reference 1 https://www.nice.org.uk/guidance/ipg485 Disclosure of Interest None Declared

Advances in Biliary Tract Disorders: Novel Biomarkers, Pharmacotherapies, Endoscopic Techniques, and Surgical Management

Biliary tract disorders encompass a wide range of benign and malignant disease processes. In this special issue, we aimed to highlight advances in novel biomarkers, pharmacotherapies, endoscopic techniques, and surgical management of a variety of biliary tract disorders. Such advances continue to lead to improved diagnostic accuracy, better therapies, and subsequently superior patient outcomes. Manuscripts selected for publication in this issue come from around the world and address clinically relevant topics and advances in biliary tract disorders, as briefly summarized below.

Tu1969 Predictors of Post-Operative Recurrence of Ileal Crohn's Disease

Introduction Long term follow up of patients resected for ileal Crohn’s (IC) disease have reported recurrence rates to range from 10–30% during the first post-operative year. Recent randomised controlled trials have shown that the “treat to target” approach based early colonoscopy to detect and treat early recurrence is crucial in maintaining remission. This study aims to identify clinical factors that predict risk of recurrence to help stratify patients that warrant early colonoscopy. Methods In a retrospective study conducted in a University Hospital with a catchment area of 1 million patients, clinical records of patients with Crohn’s disease under regular follow-up from January 2011 to November 2013 were reviewed to identify patients who underwent ileal resection. The outcome after surgery was assessed on the basis of electronic patient records that were prospectively followed up till November 2015. Results 50 patients were included in this study (median age: 34 years, male: 21 (42%)). The median duration of postoperative follow-up was 22 months. 26 (52%) patients had endoscopic or radiological evidence of recurrent disease. Probabilities of recurrence according to the Kaplan-Meier method were 22% and 41% at 1 and 2 years respectively. Univariate analysis (log-rank) showed that pre-operative dual immunosuppression with immunomodulatory and biological agents (p = 0.01), lack of response pre-operatively to at least two biological agents (p = 0.01) and previous surgery (p = 0.02) were associated with increased risk of recurrence of IC disease. Multivariate Cox hazard model demonstrated that fibrostenotic or fistulating/penetrating disease (HR = 3.55; 95% CI 1.24 to 10.19; p = 0.02), perianal disease (HR = 2.41; 95% CI 1.02 to 5.66; p = 0.04) and smoking (HR = 2.92; 95% CI 1.18 to 7.22; p = 0.02) significantly increased risk of recurrence post ileal resection and were independent predictors of relapse. Older age at diagnosis non-significantly reduced the risk of post-operative recurrence of IC disease (HR = 0.53; 95% CI 0.25 to 1.09; p = 0.086). Conclusion In addition to known risk factors we have shown that patients on dual immunosuppression and failure of two biologics pre-operatively are significant factors in predicting early recurrence. In the era of “treat to target” approach to achieve mucosal healing and sustained remission, risk stratification based on strong clinical predictors of early post-operative recurrence of Crohn’s disease will help guide timing of colonoscopy following surgery. Disclosure of Interest None Declared