Introduction

Autoimmune atrophic gastritis (AAG) leads to significant changes in the gastric mucosa, including hypo-achlorhydria and increased gastrin (G) levels, providing proliferative stimuli on the gastric mucosa (1-5).

Aims & Methods

The aim of our study is to evaluate the occurrence and characteristics of gastric polyps in AAG patients across six tertiary centers in Italy. We conducted a multicentric, cross-sectional study from January to June 2023, prospectively enrolling consecutive patients diagnosed with AAG, from January 2000 to June 2023, who underwent at least one endoscopy. Data on demographics, clinical history, biochemical profiles, serological data, and endoscopic and histopathological findings were collected.

Results

Among 612 AAG patients (73.9% female, median age 66) followed up for a median of 4 (IQR 2-7.5) years, 222 (36.3%) had at least one gastric polyp. Non-endocrine polyps (214) were found in 162 patients, including 151 (70.5%) inflammatory, 29 (13.6%) adenomatous, 18 (8.4%) fundic gland polyps, 13 (6.1%) adenocarcinomas, and one MALT lymphoma. Additionally, 108 patients (48.6% of the population with polyps and 17.6% of the overall AAG patients) presented with gastric neuroendocrine neoplasms (gNENs), 48 of whom also had non-endocrine polyps. The median polyp size was 4 (IQR 2-7) mm. Older age, smoking prevalence, and higher levels of G and chromogranin A (CgA) were associated with polyp presence. No significant differences in OLGA/OLGIM stages or H. pylori status were noted between patients with and without polyps.

Conclusion

This study represents the largest multicentric cohort of AAG patients, highlighting the significant presence of gastric polyps, including gNENs and various non-endocrine types including a not negligible proportion of patients who showed gastric adenocarcinoma. These results emphasize the importance of proactive endoscopic monitoring and comprehensive histopathological evaluation in patients with AAG, to effectively identify and manage these different gastric lesions.

References

1. Zhang H, Jin Z, Cui R, Ding S, Huang Y, Zhou L. Autoimmune metaplastic atrophic gastritis in chinese: a study of 320 patients at a large tertiary medical center. Scand J Gastroenterol. 2017;52(2):150-6.
2. Krasinskas AM, Abraham SC, Metz DC, Furth EE. Oxyntic mucosa pseudopolyps: a presentation of atrophic autoimmune gastritis. Am J Surg Pathol. 2003;27(2):236-41.
3. Kishino M, Nonaka K. Endoscopic Features of Autoimmune Gastritis: Focus on Typical Images and Early Images. J Clin Med. 2022;11(12).
4. Park JY, Cornish TC, Lam-Himlin D, Shi C, Montgomery E. Gastric lesions in patients with autoimmune metaplastic atrophic gastritis (AMAG) in a tertiary care setting. Am J Surg Pathol. 2010;34(11):1591-8.
5. Massironi S, Elvevi A, Gallo C, Laffusa A, Tortorella A, Invernizzi P. Exploring the spectrum of incidental gastric polyps in autoimmune gastritis. Dig Liver Dis. 2023.

Introduction

Crohn’s disease (CD) is characterized by discontinuous inflammation. Failure to identify skipping lesions of the terminal ileum (TI) or transmural changes can lead to incorrect management.

Aims & Methods

Eligible adult patients with CD undergoing ileo-colonoscopy and computed tomography enterography (CTE) or magnetic resonance enterography (MRE) within six months. We determined the prevalence of endoscopic skipping (normal ileum on colonoscopy but proximal small bowel inflammation on cross-sectional imaging), skip lesions (discontinuous inflammation along the gastrointestinal tract identified on cross-sectional imaging), and penetrating complications.

Results

Among 202 patients, 45 (22.3%) had endoscopic skipping proximal to TI intubation. Fifty patients (24.5%) had small bowel skip lesions, primarily in the ileum. Strictures were identified in 34 patients (16.8%) through both imaging and ileo-colonoscopy, in 21 patients (10.4%) solely through cross-sectional imaging, and in 3 patients (1.5%) solely through ileo-colonoscopy. Approximately 63.8% of stricturing cases would be missed without cross-sectional imaging. Penetrating complications, including abscesses (2.5%) and various fistula types (4.9%), were detected in 15 (7.4%) patients.

Table. Comparison between patients who had active Crohn’s disease with and without abnormal TI on colonoscopy

Conclusion

Ileo-colonoscopy missed detection of active CD in approximately one-fifth of cases due to more proximal disease location. Stricturing disease would be missed in more than half of cases if cross-sectional imaging was not performed.

Disclosure

Virginia Solitano no conflict of interests.
Sudheer Kumar Vuyyuru has received consultancy fees from Alimentiv Inc.
Achuthan Aruljothy no conflict of interests.
Maan Alkhattabi has received consulting fees from Janssen. Speaker’s fees from Janssen, Takeda & Pfizer.
Melanie Beaton has received advisory board fees from AbbVie, Astra Zeneca, Gilead,
Janssen, Novo Nordisk, Lupin, Pfizer and Takeda.
Jamie Gregor has no conflict of interests.
Zahra Kassam has received Bayer Pharmaceuticals speaker honorarium and research grant, Fusion MD speaker fees, Alimentiv Inc consulting fees.
Rocio Sedano has received consultancy fees from Alimentiv Inc.
Harry Marshall has no conflict of interests,
Darryl Ramsewak has no conflict of interests.
Michael Sey has received consultant fees from Medtronic; Research grants and speaker fees from Pendopharm; Educational grant from Cook Medical.
Vipul Jairath has received consultancy/advisory board fees from AbbVie, Alimentiv Inc., Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Reistone Biopharma, Roche, Sandoz, Second Genome, Takeda, Teva, Topivert, Ventyx, and Vividion; and speaker’s fees from, Abbvie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda, and Fresenius Kabi.

Introduction

Mirikizumab (miri), a p19-directed IL-23 antibody, showed efficacy in ulcerative colitis (UC)¹. Miri modulates transcripts associated with disease activity and anti-TNF resistance in UC and increases expression of transcripts associated with healthy mucosa². Here, we evaluate the transcription profile of patients with UC who respond to placebo (PBO, 20.6%) or miri 200mg treatment (59.7%) versus non-responders and build a model that can predict response in patients with UC.

Aims & Methods

In the phase 2 AMAC trial (NCT02589665), patients were randomized 1:1:1:1 to receive intravenous PBO (N=63), 50mg miri (N=63), or 200mg miri (n=62) with possible exposure-based dose increases or fixed 600mg miri (n=61) at Week (W)0, 4 and 8. Colonic biopsies were collected at baseline, W12, and W52. An Affymetrix HTA2.0 microarray measured gene expression. Limma comparing values at baseline and W12 determined differentially expressed genes (DEGs). DEGs maintaining their W12 expression level through W52 among responders in either the PBO and miri 200mg arms were designated as similarly expressed genes (DEGSEGs).
XGBoost models³ were trained to predict clinical response (decrease in 9-point Mayo subscore [rectal bleeding, stool frequency, endoscopy] of ≥2 points and ≥35% from baseline [BL] with either a decrease of RB subscore of ≥1 or an RB subscore of 0 or 1) using baseline levels of DEGSEGs and TNF biomarkers. Leave-one-out cross validation of the models using AMAC data and validation experiments by training on the PROTECT data⁴ then predicting in AMAC were used to evaluate our models.

Results

Miri 200mg responders were associated with 84 DEGSEGs, PBO responders were associated with 26 DEGSEGs, and 21 DEGSEGs were common to both. When using the PROTECT data as the training data and AMAC data as the validation cohort, we were able to achieve high ROC-AUC and PR-AUCs using the top 36 (FC > 1.5) miri DEGSEGs (PR-AUC=0.78), or combined (PR-AUC=0.93) gene sets as the features and found that the response prediction was significantly higher in AMAC responders vs. non-responders.

Conclusion

Baseline transcript features were predictive of clinical response in patients with UC treated with miri 200mg and our model distinguished responders from non-responders. Future studies are underway to validate this model.

References

1. Sandborn WJ, et al. Gastroenterology. 2020;158(3):537-549.e10.
2. Steere B, et al. J Crohns Colitis. 2020;S103-S104.
3. Chen T, et al. Proceedings of the 22^nd ACM SIGKDD International Conference. 2016;7285-794.
4. Hyams JS, et al. Lancet Gastroenterol Hepatol. 2017;2(12):855-868.

Disclosure

TJ and KH report no conflicts of interest. WR reports grant support and personal fees from Abbott Laboratories, AbbVie, Aesca, Centocor, Falk Pharma GmbH, Immundiagnostik, and Merck Sharp & Dohme, and personal fees from Aptalis, Celltrion, Danone Austria, Elan, Ferring, Mitsubishi Tanabe Pharma Corporation, Otsuka, PDL BioPharma, Pharmacosmos, Schering-Plough, Shire, Takeda, Therakos, Vifor, Yakult, Amgen, AM Pharma, Astellas, AstraZeneca, Avaxia, Bioclinica, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Covance, Galapagos, Genentech, Gilead Sciences, Grünenthal, ICON, Index Pharma, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millennium, Nestle, Novartis, Ocera, Pfizer, Procter & Gamble, Prometheus, Robarts Clinical Trial, Second Genome, SetPoint Medical, TiGenix, UCB, Zyngenia, and 4SC. BS, CH, NM, and VK are employees and shareholders of Eli Lilly and Company. CM is a former employee of Eli Lilly and Company. GD has served as an advisor for: AbbVie, Ablynx, Active Biotech, AgomAb Therapeutics, Allergan, AlphaBiomics, Amakem, Amgen, AM-Pharma, Applied Molecular Therapeutics, Arena Pharmaceuticals, AstraZeneca, Avaxia Biologics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb/Celgene, Celltrion, Cosmo Pharmaceuticals, Dr. Falk Pharma, DSM Pharmaceuticals, Echo Pharmaceuticals, Eli Lilly and Company, enGene, Exeliom Biosciences, Ferring Pharmaceuticals, Galapagos NV, Genentech/Roche, Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Immunic Therapeutics, Johnson & Johnson, Kintai Therapeutics, Lycera, Medimetrics, Medtronic, Merck Sharp & Dohme, Mitsubishi Pharma, Mundipharma, Nextbiotics, Novo Nordisk, Otsuka, Pfizer, PhotoPills, ProciseDx, ProDigest, Progenity, Prometheus Laboratories/Nestlé, Protagonist Therapeutics, RedHill Biopharma, Robarts Clinical Trials, Salix Pharmaceuticals, Samsung Bioepis, Sandoz, Seres Therapeutics/Nestec/Nestlé, Setpoint, Shire, Takeda, Teva, TiGenix, Tillotts Pharma AG, Topivert, Versant, and Vifor Pharma; and received speaker fees from: AbbVie, Biogen, Ferring Pharmaceuticals, Galapagos NV/Gilead Sciences, Johnson & Johnson, Merck Sharp & Dohme, Mundipharma, Norgine, Pfizer, Samsung Bioepis, Shire, Millenium/Takeda, Tillotts Pharma AG, and Vifor Pharma.

Introduction

Patients with Inflammatory Bowel Disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC) are at high risk of developing malignancies, so prevention and adherence to cancer screening may improve its detection.
The aim of this study was to assess the compliance with medical recommendations, especially primary and secondary prevention of cancer.

Aims & Methods

The aim of this study was to assess the compliance with medical recommendations, especially primary and secondary prevention of cancer.
This one-center cross-sectional study was carried out between June and December 2021r. amongst patients from the Department of Internal Medicine and Gastroenterology with IBD Division, National Health Institute of Ministry of Interior Affairs and Administrations or outpatient clinic. Patients were asked to complete anonymous questionnaire which included 42 questions concerning lifestyle, cancer risk factors, cancer history and checkups in patients with IBD. The results of the qualitative variables were expresses as frequencies and percentage. We used Fisher exact test, chi-squares test. p<0.05 was considered significant. Statistical analyses were performed with the SPSS statistical package.

Results

A total of 313 patients were enrolled into the study: 145 women and 168 men. In the group, 182 had Crohn’s disease (CD), 120 had ulcerative colitis (UC) and 11 with IBDU (unclassified IBD). Most participants had disease duration over 8 years, received biological treatment, corticoids or/and immunosuppressive therapy. Amongst respondents 17% (31) of patients with CD, 25.8% (31) with UC were overweight and 10.5% (19) with CD and 15.8% (19) with UC were obese (p= 0.017). We found that 16.3% of all respondents were smokers (79.6% (144) CD, 90.8% (109) UC and 72.7%(8); p 0.053) and 33.9% declared to consume alcohol (39.4%(71) CD, 26.9%(32) UC and 18.2%(2) IBDU; p 0.045). 25.4% were exposed to UV radiation, only 18.8% of them used sunblock. 58.8% (67) of patients with CD, 35.8% (19) and UC receiving immunosuppressants did regular laboratory tests regularly (p= 0.02). 41.4% (46) of UC, 27.1% (49) of CD and 70.0%(7) IBDU declared not to do any dermatological control (p =0.013). 77% of patients had abdominal ultrasound done. Out of 52.9% of patients who had colonoscopy recommended, only 27.3% had it performed (16.9%(30) with CD vs . 43.1%(50) with UC p< 0 .001). Most of examinations were ordered by gastroenterologists. Female patients had regular breast control (CD 78.6% (66), UC 91.2%(52) and 50% (2) IBDU p 0.034) and 93.8% (76) had gynaecological examination. 80.2% of patients knew about HPV but most declared not to be vaccinated. 17.9% of patients had urological control, but most had no important pathology detected.

Conclusion

According to our study, many patients are still exposed to risk factors, such as obesity, smoking or little physical activity, which are modifiable. Systematic control especially dermatological check-ups should be recommended. Additionally, not only gastrologists but also other specialists and GPs should remind patients about regular checkups. Primary prevention, such as HPV vaccinations, should be reminded to all patients.

References

1. Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies [published correction appears in Lancet. 2020 Oct 3;396(10256):e56]. Lancet. 2017;390(10114):2769-2778
2. Eder P, Łodyga M, Gawron-Kiszka M, et al. Guidelines for the management of ulcerative colitis. Recommendations of the Polish Society of Gastroenterology and the Polish National Consultant in Gastroenterology. Gastroenterology Review/Przegląd Gastroenterologiczny. 2023;18(1):1-42. doi:10.5114/pg.2023.125882.
3. Łodyga M, Eder P, Gawron-Kiszka M, et al. Guidelines for the management of patients with Crohn's disease. Recommendations of the Polish Society of Gastroenterology and the Polish National Consultant in Gastroenterology. Prz Gastroenterol. 2021;16(4):257-296
4. Gordon H, Biancone L, Fiorino G, et al. ECCO Guidelines on Inflammatory Bowel Disease and Malignancies [published online ahead of print, 2022 Dec 18]. J Crohns Colitis. 2022Rozich JJ, Holmer A, Singh S. Effect of Lifestyle Factors on Outcomes in Patients With Inflammatory Bowel Diseases. Am J Gastroenterol. 2020;115(6):832-840.

Introduction

Background
Lymphocyte trafficking to the inflamed gut is one of the hallmarks of Inflammatory Bowel Disease (IBD) pathology. Integrin a4b7 and its ligand MADCAM1 play an important role in targeting immune cells in the bloodstream to mucosal tissues and blocking this pathway using the anti-a4b7 monoclonal antibody Vedolizumab (VDZ) proved to be an effective treatment in IBD. However, VDZ is most efficient in treatment of Ulcerative Colitis (UC) and of colonic rather than ileal Crohn’s Disease (CD), for which the reasons have not been completely understood.

Aims & Methods

Aim:
To compare the expression of ITGA4, ITGB7 and MADCAM1 in gut tissue biopsies from small and large bowel with respect to the underlying severity of tissue inflammation.

Methods:
Differential gene expression analysis was conducted using bulk RNA Sequencing data generated from gut tissue biopsies of the large and small intestine of 611 CD and 315 UC patients enrolled in a multicentred longitudinal Study of a Prospective Adult Research Cohort with IBD (SPARC IBD) obtained from the IBD Plexus program of the Crohn’s and Colitis Foundation. Gene expression levels of ITGA4, ITGB7 and MADCAM1 were compared across ileal, colonic and rectal segments of the intestine and data were then linked to available measures of local inflammation.

Results

Results:
ITGA4, ITGB7 and MADCAM1 were expressed at comparable levels in large vs small bowel biopsies. Expression of MADCAM1 was significantly increased in both ileal and colonic biopsies from patients with moderate to severe CD based on segmental or composite endoscopy score (SES-CD) across all bowel segments. Expression of both ITGA4 and ITGB7 was similarly increased in colonic biopsies of moderate/severe CD patients, whereas only minor changes were observed for both genes in ileal biopsies. Similar findings were obtained from UC patients, where expression of MADCAM1 was significantly increased in inflamed or ulcerated biopsies from both sigmoid colon and cecum as compared to normal appearing biopsies. Expression of ITGA4 and ITGB7 was only increased in inflamed/ulcerated biopsies of the sigmoid colon but not the cecum and correlated with the modified Mayo endoscopic score (MMES).

Conclusion

Conclusion:
Our analysis suggests that influx of leukocytes to inflamed tissue via ITGA4/ITGB7 and MADCAM1 interactions is more common in the distal colon compared to proximal colon or ileum. This provides a possible mechanistic explanation as to why VDZ is most effective in patients with colonic IBD. Further work is needed to understand the differential regulation of cell trafficking to different regions of the gut.

Introduction

Inflammatory Bowel Diseases (IBD) patients have increased risk for non-alcoholic fatty liver disease (NAFLD). The pathogenesis of NAFLD in IBD patients may be complex and related to multiple factors, such as gut dysbiosis, systemic inflammation, unhealthy nutritional behavior and body composition. NAFLD can lead to severe complications, such as NASH, cirrhosis and HCC, and its incidence is increasing worldwide. Therefore, this study aimed to evaluate NAFLD prevalence among IBD patients and compare their profile with NAFLD patients.

Aims & Methods

138 IBD patients and 93 NAFLD from a public outpatient healthcare service in Brazil were included in this cross-sectional study. Patients were divided in three groups for comparison: IBD only, IBD+NAFLD and NAFLD only. The presence of NAFLD in IBD patients was assessed by ultrasonography. Exclusion criteria: preexisting liver disease in IBD group, history of alcohol intake >20g/day for women and >30g/day for men, and glucocorticoids treatment >20mg/day. Statistical analysis: descriptive statistics and association tests.

Results

In total, 58 IBD patients presented NAFLD (42.03%). Comparing the three groups, patients in NAFLD only were older (P=0.0279), presented more frequently clinical comorbidities and higher BMI (Table 1). When comparing patients “IBD+NAFLD” and “NAFLD only”, we found difference regarding BMI (p<0.0027) and liver assessment scores, such as FIB-4 Index (1,11±0,69 vs 1.67±1.57, p=0.005) and NAFLD score (-1,34±1,84 vs 1.94±1.39 p=0.0467). Also, in biochemical tests, it was observed difference in platelet count (P=0.0009), ALT (P<0.0005), AST (P<0.0001), GGT (P<0.0001), ferritin (P<0.0001), glycosylated hemoglobin (P<0.0087), HDL cholesterol (P<0.0001) and insulin levels (P<0.0001). Mostly, patients in both groups presented moderate steatosis (46.55% vs 44.09%, p=0.0639).

Table 1. Comparison among IBD only, IBD+NAFLD and NAFLD only groups.

Conclusion

We observed a high prevalence of NAFLD in patients with IBD (42.03%). NAFLD group had higher levels of BMI, AST, ALT, fasting glucose and blood insulin, in all comparisons – both groups and when compared to IBD+NAFLD group exclusively. We observed that patients without IBD presents higher levels of conditions associated to metabolic syndrome.

References

1. Magro F, Gionchetti P, Eliakim R, et al. J Crohns Colitis. 2017; 11(6):649-670.
2. Principi M et al. Inflamm Bowel Dis. 2018;24(7):1589-1596