Novel Biomarkers and the Future Potential of Biomarkers in Inflammatory Bowel Disease.

There is increasing importance placed upon noninvasive assessment of gut inflammation. These tools are likely to be the key in differentiating intestinal inflammatory disease from functional disorders and in monitoring the response to intervention in individuals with known inflammatory conditions. Although various noninvasive markers are currently available, they have limitations and do not provide ideal utility. This review focuses on emerging markers of gut inflammation, highlighting the potential of specific markers

An Extremes of Phenotype Approach Confirms Significant Genetic Heterogeneity in Patients with Ulcerative Colitis

Background and Aims: Ulcerative colitis [UC] is a major form of inflammatory bowel disease globally. Phenotypic heterogeneity is defined by several variables including age of onset and disease extent. The genetics of disease severity remains poorly understood. To further investigate this, we performed a genome wide association [GWA] study using an extremes of phenotype strategy. Methods: We conducted GWA analyses in 311 patients with medically refractory UC [MRUC], 287 with non-medically refractory UC [nonMRUC] and 583 controls. Odds ratios [ORs] were calculated for known risk variants comparing MRUC and non-MRUC, and controls. Results: MRUC–control analysis had the greatest yield of genome-wide significant single nucleotide polymorphisms [SNPs] [2018], including lead SNP = rs111838972 [OR = 1.82, p = 6.28 × 10−9] near MMEL1 and a locus in the human leukocyte antigen [HLA] region [lead SNP = rs144717024, OR = 12.23, p = 1.7 × 10−19]. ORs for the lead SNPs were significantly higher in MRUC compared to non-MRUC [p < 9.0 × 10−6]. No SNPs reached significance in the non-MRUC–control analysis (top SNP, rs7680780 [OR 2.70, p = 5.56 × 10−8). We replicate findings for rs4151651 in the Complement Factor B [CFB] gene and demonstrate significant changes in CFB gene expression in active UC. Detailed HLA analyses support the strong associations with MHC II genes, particularly HLA-DQA1, HLA-DQB1 and HLA-DRB1 in MRUC. Conclusions: Our MRUC subgroup replicates multiple known UC risk variants in contrast to non-MRUC and demonstrates significant differences in effect sizes compared to those published. Non-MRUC cases demonstrate lower ORs similar to those published. Additional risk and prognostic loci may be identified by targeted recruitment of individuals with severe disease.Sally Mortlock, Anton Lord, Grant Montgomery, Martha Zakrzewski, Lisa A.Simms, Krupa Krishnaprasad, Katherine Hanigan, James D. Doecke, Alissa Walsh, Ian C. Lawrance, Peter A.Bampton, Jane M. Andrews, Gillian Mahy, Susan J. Connor, Miles P.Sparrow, Sally Bell, Timothy H. Florin, Jakob Begun, Richard B. Gearry, Graham L. Radford-Smit

Management of Patients With Crohn's Disease and Ulcerative Colitis During the Coronavirus Disease-2019 Pandemic: Results of an International Meeting

The International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) is the only global organization devoted to the study of and management of the inflammatory bowel diseases (IBDs), namely, Crohn?s disease and ulcerative colitis. Membership is composed of physician-scientists who have established expertise in these diseases. The organization hosts an annual meeting and a number of working groups addressing issues of the epidemiology of IBD, diet and nutrition, and the development and use of treatments for IBD. There are currently 89 members of IOIBD representing 26 different countries. The organization has taken particular interest in the coronavirus disease-2019 (COVID-19) pandemic and how it may affect the IBD patient population. This document summarizes the results of 2 recent virtual meetings of the group and subsequent expert guidance for patients and providers

Are faecal markers good indicators of mucosal healing in inflammatory bowel disease?

AIM: To review the published literature concerning the accuracy of faecal inflammatory markers for identifying mucosal healing. METHODS: Bibliographical searches were performed in MEDLINE electronic database up to February 2015, using the following terms: “inflammatory bowel disease”, “Crohn´s disease”, “ulcerative colitis”, “faecal markers”, “calprotectin”, “lactoferrin”, “S100A12”, “endoscop*”, “mucosal healing”, “remission”. In addition, relevant references from these studies were also included. Data were extracted from the published papers including odds ratios with 95%CI, P values and correlation coefficients. Data were grouped together according to each faecal marker, Crohn’s disease or ulcerative colitis, and paediatric compared with adult study populations. Studies included in this review assessed mucosal inflammation by endoscopic and/or histological means and compared these findings to faecal marker concentrations in inflammatory bowel diseases (IBD) patient cohorts. Articles had to be published between 1990 and February 2015 and written in English. Papers excluded from the review were those where the faecal biomarker concentration was compared between patients with IBD and controls or other disease groups, those where serum biomarkers were used, those with a heterogeneous study population and those only assessing post-operative disease. RESULTS: The available studies show that faecal markers, such as calprotectin and lactoferrin, are promising non-invasive indicators of mucosal healing. However, due to wide variability in study design, especially with regard to the definition of mucosal healing and evaluation of marker cut offs, the available data do not yet indicate the optimal roles of these markers. Thirty-six studies published between 1990 and 2014 were included. Studies comprised variable numbers of study participants, considered CD (15-164 participants) or UC (12-152 participants) separately or as a combined group (11-252 participants). Eight reports included paediatric patients. Several indices were used to document mucosal inflammation, encompassing eleven endoscopic and eight histologic grading systems. The majority of the available reports focused on faecal calprotectin (33 studies), whilst others assessed faecal lactoferrin (13 studies) and one study assessed S100A12. Across all of the biomarkers, there is a wide range of correlation describing the association between faecal markers and endoscopic disease activity (r values ranging from 0.32 to 0.87, P values ranging from < 0.0001 to 0.7815). Correlation coefficients are described in almost all studies and are used more commonly than outcome measures such as sensitivity, specificity, PPV and/or NPV. Overall, the studies that have evaluated faecal calprotectin and/or faecal lactoferrin and their relationship with endoscopic disease activity show inconsistent results. CONCLUSION: Future studies should report the results of faecal inflammatory markers in the context of mucosal healing with clear validated cut offs

Association of the HLA locus and TNF with type I autoimmune hepatitis susceptibility in New Zealand Caucasians

10.1186/2193-1801-2-355SpringerPlus211-

Serious infective complications associated with anti-TNF alpha therapy in inflammatory bowel disease

Background: Anti-TNFαmedications are effective in the management of patients with difficult Crohn’s disease (CD) and ulcerative colitis/IBDU(UC/IBDU). They are, however, associated with an increased risk of tuberculosis (TB) reactivation, initial TB infection, and potentially other bacterial, viral or fungal infections. Aims: To examine the Australasian experience of TB and serious infective complications in IBD patients treated with an anti-TNFα. Methods: Data was collected from eight sites across Australia and New Zealand specialising in IBD management. Overall IBD patient numbers managed, patient numbers ever treated with an anti-TNFα, and patients suffering TB, or a serious infection while receiving anti-TNFαtherapy were analysed. A serious infection was defined as ‘an infection requiring hospital admission’. Patient demographics, concurrent IBD medications, the anti-TNFαmedication used, time on the anti-TNFα, infection type and infection outcome was also collected. Results: A total of 5613 IBD patients (2904 CD, 2709 UC/IBDU) were managed across the centers. Anti-TNFαtherapy was used in 16.9% of CD(491; 442-infliximab, 94-adalimumab, 45-both) and 3.7% of UC/IBDU patients (100 UC/IBDU; 94-infliximab, 14-adalimumab, 8-both). There were no cases of reactivation of latent TB and no new cases reported. There were nine serious infections (4M/5F, 1 UC/IBDU/8 CD, average 36.1 years, range 14–57 years). Infections occurred in three patients receiving 24 months of an anti-TNFα. All these patients were receiving additional immunosuppressive (IS) medication: 2-pred, 1-pred/AZA, 2-AZA, 1-methotrexate (MTX), 1-pred/MTX, 1-pred/AZA/MTX and 1-pred/MTX/mycophenolate mofetil. Seven of the infections occurred while on an anti-TNFαand two within 3 months of the last treatment. There were two primary varicella zoster, one Pneumocysits carnii peunmonia, one UTI with enterobacteraerogenes, and five infections where no organ-ism was identified (1 pneumonia, one diverticular abscess, one conjunc-tivitis and two unidentified source). All infections resolved. Conclusion: TB does not appear to be a problem with anti-TNFα therapy in Australasia. Infections, resulting in a hospital admission, are low occur-ring in only 1.8% of patients receiving anti-TNFαtherapy, but all those patients were also on other IS medications. All the infections were successfully treated.IC Lawrance, Pabampton, M Sparrow, RB Gearry, RW Leong, JM Andrews, THJ Florin, A Croft, And GL Radford-Smit

Low-FODMAP Diet Is Associated With Improved Quality of Life in IBS Patients-A Prospective Observational Study

BACKGROUND: The low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet is effectively manages irritable bowel syndrome (IBS) symptoms. Long-term low-FODMAP studies rarely report quality of life (QoL). We aimed to determine the effect of low-FODMAP diet on long-term QoL, gastrointestinal (GI) and non-GI symptoms in IBS patients. METHODS: A prospective observational study of IBS patients referred for low-FODMAP dietary advice was performed. The primary outcome of QoL and secondary outcomes of GI symptoms, anxiety/depression, fatigue, sleep quality, and happiness were obtained at baseline, 6 weeks (T6), and 6 months (T26). RESULTS: 111 patients were recruited. 91.0%, 71.6%, and 50.5% of participants completed baseline, T6, and T26 assessments, respectively. There were significant improvements in QoL from baseline at T6 and T26 (both P < 0.001). Significant reductions were seen in GI symptoms at T6 and T26 (both P < 0.001), fatigue at T6 and T26 (both P < 0.003), and anxiety at T6 and T26 (both P < 0.007), compared with baseline. A significant reduction was seen for depression (P < 0.010) from baseline at T26, and a significant increase was seen for both happiness and vitality (both P < 0.04) from baseline at T26. There was a significant correlation between GI symptom response and change in QoL, anxiety, depression, and fatigue (all P < 0.034). CONCLUSION: Low-FODMAP diet was associated with improved long-term QoL and GI symptoms, reduced fatigue and anxiety/depression, and increased happiness and vitality. These data support a wider range of benefits for IBS patients consuming a low-FODMAP diet

Level of UV exposure, skin type, and age are more important than thiopurine use for keratinocyte carcinoma development in IBD patients

BACKGROUND:Retrospective studies observe an increased risk of keratinocyte carcinomas (KCs) in patients with inflammatory bowel disease (IBD) on thiopurine (TP) medication. The role of traditional risk factors such as skin type and sun protection behavior has not been studied in this population. This study aimed to examine traditional KC risk factors and thiopurine use on skin cancer development in an IBD cohort. METHODS:Consecutive IBD patients were recruited from four specialist centers in Australia and New Zealand, each with varying UV exposure indices. Data pertaining to race, skin color, freckling and sun protection behavior, dose of TP therapy, and skin cancer development were elicited through a self-reported questionnaire. RESULTS:A total of 691 IBD patients were included with 62 reporting KC development. Thiopurine usage was similar among patients who developed skin cancer compared with those who did not (92% vs. 89%, p = 0.3). There was no statistically significant association between KC development and TP dose or 6-thioguanine nucleotide levels. In multivariate modeling, four factors were independently and significantly associated with KC: age over 61 years old versus less than 30 years old (OR 6.76; 95% CI 2.38-19.18), residing in Brisbane versus Christchurch (OR 3.3; 95% CI 1.6-6.8), never staying in the shade versus staying in the shade ≥ 50% of the time (OR 3.8; 95% CI 1.4-10.5), and having a skin type that never tanned versus other skin types (OR 6.9; 95% CI 2.9-16.0). CONCLUSION:Skin type, age, and sun protection behavior are more important risk factors for KC development than thiopurine medication use in this IBD population.Yang Wu, Simon Ghaly, Stephen Kerr, Bryce Jackson, Katherine Hanigan ... Peter A. Bampton ... et al

Crohn's disease and smoking: Is it ever too late to quit?

Background: Smoking increases CD risk. The aim was to determine if smoking cessation at, prior to, or following, CD diagnosis affects medication use, disease phenotypic progression and/or surgery. Methods: Data on CD patients with disease for ≥. 5. yrs were collected retrospectively including the Montreal classification, smoking history, CD-related abdominal surgeries, family history, medication use and disease behaviour at diagnosis and the time when the disease behaviour changed. Results: 1115 patients were included across six sites (mean follow-up-16.6. yrs). More non-smokers were male (p. = 0.047) with A1 (p