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MAGNETIC RESONANCE IMAGING (MRI) SHOWS CHANGES IN BOWEL MORPHOLOGY AND MOTILITY IN SHORT BOWEL SYNDROME WITH INTESTINAL FAILURE (SBS-IF) AND COLON-IN-CONTINUITY (CIC) AFTER TREATMENT WITH THE LONG-ACTING GLUCAGON-LIKE PEPTIDE-2 (GLP-2) ANALOG APRAGLUTIDE

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Introduction

SBS-IF is a severe organ failure with long-term parenteral support (PS) dependence. In the first years after extensive surgery, spontaneous structural (elongation of intestinal villi and crypts) and functional (incl. motility) intestinal changes occur, stimulating a more efficient nutrient and fluid absorption in the remnant bowel. GLP-2 analogs are hypothesized to boost intestinal adaptation resulting in increased intestinal absorption and reduced PS needs. Apraglutide (APRA) is a long-acting GLP-2 analog in development for SBS-IF. We investigated the effect of APRA at 52 weeks (W) on bowel morphology and motility based on magnetic resonance imaging (MRI).

Aims & Methods

STARS Nutrition is a 52-W multicenter, open-label, phase 2 study in adult SBS-IF-CiC pts receiving weekly subcutaneous APRA injections (5mg). We hypothesized that APRA treatment would lead to thickening of the intestinal mucosa, intestinal lengthening, reduced bowel dilatation and reduced intestinal motility. Therefore, MRI scans of the abdomen, incl. cine sequences, after oral intake of a mannitol solution (600mL) were performed at baseline and at 4W, 24W and 48W of treatment. Morphology parameters were measured on static MRI sequences; GI Quant software was used to quantify motility on cine MRI sequences. Data are presented as median (IQR). Nominal p-values are calculated using Wilcoxon matched-pairs signed rank tests with significance set at 0.05.

Results

Nine pts were included and comprise the full study population. While the numerically increased colon length failed to reach significance, small bowel length increased significantly from 29.7 to 40.7 cm (p=0.012) at 48W. Duodenal wall thickness increased by 0.8 (0.2;1.2) mm (p=0.020). There were no diameter changes in the small bowel nor colon. Changes in motility were evaluated using data from 7 pts, due to missing data. Over time, small bowel motility gradually reduced, albeit not significant. Motility in the proximal colon was significantly reduced at 48W. In the distal colon, decreased motility was observed at 4W and 24W, but returned to baseline level at 48W.

Conclusion

Using static and cine MRI sequences in pts with SBS-IF-CIC, STARS Nutrition shows that APRA treatment was associated with small bowel lengthening and increased duodenal wall thickness suggesting an intestinotrophic effect. Both effects may contribute to an increased surface area for absorption. The reduced motility, especially in the proximal colon may reduce transit time, allowing more time for absorption of nutrients, fluids and electrolytes; and reduced fecal output. Whether bowel lengthening results from a direct effect of APRA vs. changes in motility with passive elongation is subject of further investigation.

Disclosure

Astrid Verbiest, Mark Krogh Hvistendahl, Ragna Vanslembrouck, Ronald Peeters, Riccardo Sartoris – nothing to declare.
Palle Bekker Jeppesen – received grants/research support/honoraria or consultation fees from Agomab, Albumedix A/S, ArTara Therapeutics, Bainan Biotech, Baxter, Coloplast, Ferring, Fresenius Kabi, GLyPharma, Naia Pharma, NPS Pharmaceuticals, NorthSea Therapeutics, Shire, Takeda, The Novo Nordisk Foundation, Therachon, VectivBio and Zealand Pharma.
Francisca Joly – has received grants/research support/honoraria or consultation fees from Agomab, Baxter, Fresenius Kabi, Nestlé Health Sciences, BBraun, Theradial, Mayoli, Biocodex, mobile3e Consulting, Carembouche, NPS Pharmaceuticals, NorthSea Therapeutics, Shire, Takeda, Therachon, VectivBio and Zealand Pharma.
Tim Vanuytsel – has served on the speaker bureau for Abbott, Agomab, Baxter, Biocodex, Dr. Falk Pharma, Fresenius Kabi, Ipsen, Menarini, Microbiotica, MyHealth, Remedus, Takeda, Truvion, VectivBio and Zealand Pharma. TV has provided clinical advice to Baxter, Danone, Dr. Falk Pharma, MyHealth, NorthSea Therapeutics, Shire, Therachon, Takeda, VectivBio, Zealand Pharma. TV has received research grants from Danone, MyHealth, Takeda and VectivBio.
Federico Bolognani, Carrie Li and Nader N. Youssef – employees of VectivBio/Ironwood.

This research was supported by VectivBio AG/Ironwood.

MAGNETIC RESONANCE IMAGING (MRI) SHOWS CHANGES IN BOWEL MORPHOLOGY AND MOTILITY IN SHORT BOWEL SYNDROME WITH INTESTINAL FAILURE (SBS-IF) AND COLON-IN-CONTINUITY (CIC) AFTER TREATMENT WITH THE LONG-ACTING GLUCAGON-LIKE PEPTIDE-2 (GLP-2) ANALOG APRAGLUTIDE

Astrid Verbiest 1, Alex Menys 2, Ragna Vanslembrouck 3, Ronald Peeters 3, Riccardo Sartoris 4, Mark Krogh Hvistendahl 5, Federico Bolognani 6, Carrie Li 6, Nader N. Youssef 6, Palle Bekker Jeppesen 5, Francisca Joly 4, Tim Vanuytsel 1

1 University of Leuven, Leuven, Belgium|||University Hospitals Leuven, Leuven, Belgium

2 Motilent, London, United Kingdom

3 University Hospitals Leuven, Leuven, Belgium

4 Hôpital Beaujon, Clichy, France

5 Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

6 VectivBio/Ironwood, Basel, Switzerland

Event

UEG Week Vienna 2024

Topics

Mechanisms & Personalised Medicine Neurogastroenterology & Motility Radiology & Imaging Small Intestine & Nutrition

Submission format

Abstract

Session

Short bowel syndrome

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

UEG Podcast Episode

UEG Podcast

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Best of UEG Week - Endoscopy with Manmeet Matharoo

Manmeet Matharoo, Egle Dieninyte - Misiune

Topics

Endoscopy

Published

2025

UEG Presentation

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Panel discussion: Liver and pregnancy - Beware of dangerous liaisons

Event

UEG Postgraduate Teaching Programme Berlin 2025

Topics

Hepatobiliary Paediatrics

Session

Liver and pregnancy: Beware of dangerous liaisons

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Standards and Guidelines

Clinical Practice Guideline

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Main recommendations

The following recommendations should only be applied after a thorough diagnostic evaluation including a contrast- enhanced computed tomography (CT) scan.

1 ESGE recommends colonic stenting to be reserved for patients with clinical symptoms and radiological signs of malignant large-bowel obstruction, without signs of perforation. ESGE does not recommend prophylactic stent placement.
Strong recommendation, low quality evidence.

2 ESGE recommends stenting as a bridge to surgery to be discussed, within a shared decision-making process, as a treatment option in patients with potentially curable left-sided obstructing colon cancer as an alternative to emergency resection.
Strong recommendation, high quality evidence.

3 ESGE recommends colonic stenting as the preferred treatment for palliation of malignant colonic obstruction.
Strong recommendation, high quality evidence.

4 ESGE suggests consideration of colonic stenting for malignant obstruction of the proximal colon either as a bridge to surgery or in a palliative setting.
Weak recommendation, low quality evidence.

5 ESGE suggests a time interval of approximately 2 weeks until resection when colonic stenting is performed as a bridge to elective surgery in patients with curable left-sided colon cancer.
Weak recommendation, low quality evidence.

6 ESGE recommends that colonic stenting should be performed or directly supervised by an operator who can demonstrate competence in both colonoscopy and fluoroscopic techniques and who performs colonic stenting on a regular basis.
Strong recommendation, low quality evidence.

7 ESGE suggests that a decompressing stoma as a bridge to elective surgery is a valid option if the patient is not a candidate for colonic stenting or when stenting expertise is not available.
Weak recommendation, low quality evidence.

Self-expandable metal stents for obstructing colonic and extracolonic cancer: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2020

Jeanin van Hooft

Publisher

European Society of Gastrointestinal Endoscopy

Guideline

Clinical Practice Guideline

Topics

Digestive Oncology Endoscopy

Citation

Endoscopy. 2020 May;52(5):389-407

Published

2020

UEG Poster

Standard Poster

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Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction with alcohol-related steatotic liver disease (MetALD) are two separate entities within the spectrum of steatotic liver disease (SLD).

Aims & Methods

This meta-analysis aims to compare the risks of hepatic and extrahepatic outcomes between MASLD and MetALD. We systematically searched for observational cohort studies published up to March 1, 2025, comparing clinical outcomes between individuals with MASLD and MetALD. The primary outcome was liver-related events, while secondary outcomes included hepatocellular carcinoma (HCC), liver-related mortality, cardiovascular events, extrahepatic cancers, and all-cause mortality. We used random-effect models to calculate pooled hazard ratios (HRs) with 95% confidence intervals (95% CI).

Results

Twenty-four studies involving 11,396,962 individuals were analyzed (9,622,716 with MASLD and 1,774,246 with MetALD). Individuals with MetALD had significantly higher risks of liver-related events (HR 1.62, 95% CI 1.16-2.25, p=0.02) and HCC (HR 1.33, 95%CI 1.00-1.77, p=0.04) than those with MASLD. The risk of extrahepatic cancers was also increased in MetALD (HR 1.03, 95% CI 1.01-1.06, p<0.001), while the rates of cardiovascular events (HR 0.96, 95% CI 0.85-1.09, p=0.48), extrahepatic cancer-related mortality (HR 1.44, 95% CI 0.97-2.15, p=0.07), and all-cause mortality (HR 1.08, 95% CI 0.97-1.19, p=0.14) did not differ between these two conditions.

Conclusion

MetALD confers a higher risk of liver-related outcomes, HCC, and extrahepatic cancers than MASLD, while all-cause mortality and cardiovascular risk are similar between the two conditions. These findings emphasize the need for distinct clinical strategies for these related yet different entities within the SLD spectrum and highlight the importance of conducting pharmacological clinical trials in this context.

Disclosure

Nothing to disclose

COMPARATIVE EFFECTS OF METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE AND METABOLIC AND ALCOHOL-ASSOCIATED STEATOTIC LIVER DISEASE (METALD) ON RISK OF HEPATIC AND EXTRA-HEPATIC OUTCOMES: A META-ANALYSIS

Ciro Celsa 1, Grazia Pennisi 2, Adele Tulone 1, Giacinta Ciancimino 1, Marco Vaccaro 1, Fabiana Pecorella 1, Gabriele Di Maria 1, Marco Enea 1, Calogero Camma 1, Salvatore Petta 1

1 University of Palermo, Palermo, Italy

2 Policlinico Paolo Giaccone, Palermo, Italy

Conference

UEG Week Berlin 2025

Topics

Hepatobiliary

Submission format

Abstract

Session

MASLD: Clinical aspects, experimental and pathology (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Presentation

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Drug management in necrotising pancreatitis

Jacob Hamm 1

1 University Medical Center Goettingen, Goettingen, Germany

Event

UEG Week Berlin 2025

Topics

Endoscopy Pancreas

Session

Therapy update: Acute severe pancreatitis – It's all about timing!

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Presentation

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CROHN'S DISEASE AND ULCERATIVE COLITIS EXHIBIT PRE-DIAGNOSTIC ANTIBODY SIGNATURES WITH SHARED AND DIVERGENT CHANGES TOWARDS DISEASE ONSET

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Introduction

Inflammatory bowel diseases (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a chronic debilitating. Current clinical practice is focused on managing disease flares and complications, requiring lifelong medical treatment and/or surgery. However, a paradigm shift in IBD care is needed, moving from treatment of established disease towards creating opportunities for prevention of disease development. Such strategies recently proved successful in rheumatoid arthritis and type 1 diabetes. Before being able to achieve this, however, preclinical disease biomarkers are urgently needed. IBD is characterized by unique immunological changes early in development. Although >300 IBD-specific antibody responses have been identified¹, systemic antibody epitope repertoires of preclinical IBD remain elusive. This study aimed to profile systemic antibody responses at unprecedented depth in individuals before and after the onset of IBD, aiming to identify preclinical disease biomarkers.

Aims & Methods

This study included individuals participating in the Lifelines Cohort Study, a large prospective population-based cohort study in the Netherlands including 167,000 individuals with longitudinal follow-up. Participants without IBD at baseline were screened for any reported IBD diagnosis during follow-up (2006-2021). Individuals who reported IBD during follow-up and with available serum samples were included. Samples at baseline (pre-diagnosis) and during follow-up (post-diagnosis) were used to profile antibody repertoires against 344,000 rationally selected microbial-, food-, and immune antigens using phage-display immunoprecipitation sequencing (PhIP-Seq).

Results

A total of 178 new-onset cases with IBD were identified. Median follow-up time until diagnosis was 3.9 (IQR: 3.4-4.3) years. Most individuals newly developed UC (n=123, 69.1%), followed by CD (n=44, 24.7%), and undetermined IBD (IBD-U, n=11, 6.2%). A total of 5,174 antibody responses were observed in 5-95% of participants. Fifty-nine antibodies were differentially abundant (FDR<0.05) pre-diagnosis vs. post-diagnosis, 14 of which (24%) were previously reported in established IBD¹. Thirteen were more (22%) and 46 less (78%) frequently observed post-diagnosis. Individuals developing IBD exhibited reduced frequencies of antibody responses against EBV-associated peptides post-diagnosis, e.g. Epstein-Barr nuclear antigen-1 (EBNA-1) and capsid protein V26, and other herpesviruses including varicella-zoster virus (VZV), herpes simplex virus type 1 (HSV-1), and noroviruses. Conversely, significantly increased antibody responses were observed against bacterial flagellins (notably from Lachnospiraceae and pathogenic (e.g. Legionella) bacteria) in individuals developing CD, already before disease onset. Individuals developing UC showed elevated antibody responses mainly against viruses (e.g. human adenovirus C, enteroviruses B/C) and particular pathogenic bacterial species (e.g. pneumococcal histidine triad proteins) post-diagnosis compared to pre-diagnosis.

Conclusion

This study represents the first comprehensive and high-resolution analysis of the exact antigenic nature of systemic antibody responses changing during the transition from preclinical to established IBD. Distinct antibody responses appear years before IBD diagnosis, indicating potential involvement in pre-clinical disease development. Furthermore, post-diagnosis, lower frequencies of antibody responses against EBV may suggest reduced immunogenicity against this virus in early disease pathogenesis.

References

1. Bourgonje et al. Immunity. 2023.

CROHN'S DISEASE AND ULCERATIVE COLITIS EXHIBIT PRE-DIAGNOSTIC ANTIBODY SIGNATURES WITH SHARED AND DIVERGENT CHANGES TOWARDS DISEASE ONSET

Arno R. Bourgonje 1, Sergio Andreu-Sánchez 2, Ranko Gacesa 2, Gabriel Innocenti 3, Iris N. Kalka 4, Shelley Klompus 4, Sigal Leviatan 4, Adina Weinberger 4, Bert van der Vegt 2, Jingyuan Fu 2, Eran Segal 4, Alexandra Petrovna Zhernakova 2, Thomas Vogl 3, Rinse K. Weersma 2

1 University Medical Center Groningen, Groningen, Netherlands|||Icahn School of Medicine at Mount Sinai, New York, United States

2 University Medical Center Groningen, Groningen, Netherlands

3 Medical University of Vienna, Vienna, Austria

4 Weizmann Institute of Science, Rehovot, Israel

Event

UEG Week Vienna 2024

Topics

IBD

Submission format

Abstract

Session

Opening Plenary

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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