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MUCOSA-ASSOCIATED COLLAGENOUS COLITIS MICROBIOTA IN-DEPTH ANALYSIS IDENTIFIES POTENTIAL DISEASE TRIGGERS

Philipp Rausch 1, Mario Pérez-Manrique 2, Andreas Münch 3, Corinna Bang 1, Andre Franke 1, Philip Rosenstiel 2, Mauro D'Amato 4,5, Celia Escudero-Hernández 2

Affiliations

1 Kiel University, Kiel, Germany

2 Kiel University, University Hospital Schleswig-Holstein, Kiel, Germany

3 Linköping University, Linköping, Sweden

4 Center of Cooperative Research in Biosciences CICbioGUNE, Derio, Spain

5 LUM University, Bari, Italy

Summary

AI Generated

Shotgun metagenomic analysis of subepithelial mucosa in collagenous colitis found overall microbial similarity to healthy controls but identified specific bacterial associations including biofilm-forming Anoxybacillus and Barnesiella in disease samples.

Laser microdissection was used to isolate subepithelial mucosa from formalin-fixed paraffin-embedded samples of collagenous colitis patients (n=7-10) and healthy controls for shotgun metagenomic sequencing.
Bray-Curtis and Jaccard similarity coefficients showed that collagenous colitis subepithelial microbiome was similar to healthy controls, though microbial metabolic pathways and molecular functions could differ.
Microbiota associated with collagenous colitis included Anoxybacillus and Barnesiella, while healthy controls were associated with Bacteroides, Leuconostoc, and Lactobacillus.
The authors suggest their results point to a relation of collagenous colitis with biofilm-forming bacteria (Anoxybacillus) and bacteria affecting colitis development variability (Barnesiella), requiring validation and follow-up.
This work may interest researchers investigating microbial triggers in microscopic colitis and mucosal microbiome analysis methods.

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This summary was generated by an AI large language model based on the content transcript. It is for informational purposes only and should not be considered a substitute for clinical judgment. Always rely on your professional expertise and the full clinical context when making clinical decisions.

Abstract

Introduction

Collagenous colitis (CC) is a debilitating, non-destructive inflammatory bowel disease (IBD) that causes intense watery, non-bloody diarrhoea. The abnormal immune response is thought to be initiated by deficient tolerance to commensal gut microbiota, and fecal sample analyses indicate similarities with classic IBD forms as ulcerative colitis and Crohn’s disease. Yet, the exact members of the microbiome that might trigger and maintain the disease remain unknown.

Aims & Methods

To identify primary microbial triggers of CC pathogenesis that could directly interact with intestinal epithelial and submucosal cells, we isolated subepithelial mucosa from CC and healthy control (Hc) formalin-fixed paraffin-embedded samples (n=7-10) by using a laser microdissection microscope (PALM MicroBeam LCM, Zeiss, Germany). Isolated nucleic acids were sequenced using shotgun metagenomics in a NovaSeq 6000 platform (Illumina, USA). Microbial communities were identified using MetaPhlan3/4, and microbial metabolic and molecular function pathways using Humann3.2 algorithms.

Results

Bray-Curtis and Jaccard similarity coefficients showed that CC subepithelial microbiome was similar to that from Hc samples. Still, further analyses indicated that microbial metabolic pathways and molecular functions could differ. Microbiota that was associated with CC included Anoxybacillus and Barnesiella, whereas microbiota associated with Hc comprised Bacteroides, Leuconostoc and Lactobacillus.

Conclusion

Mucosa-associated microbiota in CC did not significantly differ from healthy microbiota. However, our results point to a relation of CC with bacteria that form biofilms (Anoxybacillus) and affect the variability of colitis development (Barnesiella). Thus, validation and further follow-up of these results could help us identify CC triggers in the future.

References

Carstens A. The Gut Microbiota in Collagenous Colitis Shares Characteristics With Inflammatory Bowel Disease-Associated Dysbiosis. Clin Transl Gastroenterol. 2019 Jul;10(7):e00065

Disclosure

AM has received salary for consultancies from Tillotts Pharma AG, Ferring, Vifor and Dr Falk Pharma; speaker’s honoraria from Tillotts Pharma AG and Vifor. The remaining authors declare no conflicts of interest.

Conference

UEG Week Copenhagen 2023

Topics

IBD

Submission format

Abstract

Session

PP 05 IBD (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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ASSOCIATIONS BETWEEN DIASTOLIC AND SYSTOLIC DYSFUNCTION, VALVULAR HEART DISEASE, AND CIRRHOTIC CARDIOMYOPATHY WITH INTRAVASCULAR VOLUME OVERLOAD AFTER ALBUMIN INFUSION IN PATIENTS WITH LIVER CIRRHOSIS

Annalisa Berzigotti

Management of gastric metaplasia: Be aware of autoimmune gastritis

Judith Honing

LOW RECURRENCE RATES AFTER ENDOSCOPIC ERADICATION THERAPY OF BARRETT'S NEOPLASIA: LONG-TERM FOLLOW-UP RESULTS FROM THE NATIONWIDE DUTCH BARRETT'S REGISTRY

Roos E. Pouw

Large language model use for gastroenterology: Should we use it already, or is it too early given regulation and lacking data?

Omer Ahmad

STENOVA TRIAL UPDATE: OPEN-LABEL EXTENSION OF ONTUNISERTIB IN FIBROSTENOSING CROHN’S DISEASE WITH OBJECTIVE IMAGING EFFICACY ASSESSMENTS

Philippe Wiesel

SARCOPENIA AS AN INDEPENDENT DOMAIN IN CIRRHOSIS: ASSOCIATION WITH DISEASE SEVERITY AND SEX-SPECIFIC DIFFERENCES

Gagik Hakobyan

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ASSOCIATIONS BETWEEN DIASTOLIC AND SYSTOLIC DYSFUNCTION, VALVULAR HEART DISEASE, AND CIRRHOTIC CARDIOMYOPATHY WITH INTRAVASCULAR VOLUME OVERLOAD AFTER ALBUMIN INFUSION IN PATIENTS WITH LIVER CIRRHOSIS

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ASSOCIATIONS BETWEEN DIASTOLIC AND SYSTOLIC DYSFUNCTION, VALVULAR HEART DISEASE, AND CIRRHOTIC CARDIOMYOPATHY WITH INTRAVASCULAR VOLUME OVERLOAD AFTER ALBUMIN INFUSION IN PATIENTS WITH LIVER CIRRHOSIS

Fabio Brazerol 1, Daniel Segna 1, Jaime Bosch 1,2, Stefano De Marchi 1, Annalisa Berzigotti 1

Affiliations

1 Inselspital Bern and University of Bern, Bern, Switzerland, Bern, Switzerland

2 University of Bern, Bern, Switzerland

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Abstract

Introduction

Current guidelines recommend intravenous (IV) albumin as a treatment of various complications of decompensated cirrhosis, but recent data point towards clinically relevant volume overload post-infusion in this population. A prospective cohort study assessing point-of-care ultrasound (POCUS) of the inferior vena cava (IVC) found potentially severe intravascular volume overload in almost 20% of patients after albumin. However, it is still unknown whether underlying cardiac function may predict post-infusion hypervolemia and short to mid-term clinical outcomes.

Aims & Methods

In this retrospective analysis of 54 individual adults with cirrhosis receiving IV albumin, we assessed associations between transthoracic echocardiography (TTE) parameters, IVC-derived potential volume overload using POCUS, and clinical outcomes during a period of 6 months. TTE parameters were extracted from examinations within 3 months of inclusion. Any volume overload was defined as maximum IVC diameter (IVC_max) >2.1cm and IVC collapsibility index (IVCCI) < 50%; severe overload as IVC_max > 2.1cm and IVCCI < 20%. Potential associations between TTE parameters and any or severe volume overload and clinical outcomes up to 6 months (p<0.10) in univariable regression analyses were consequently analyzed in multivariable regression models adjusting for age, sex, and model of end stage liver disease (MELD).

Results

Among 76 POCUS measurements from 54 patients (female 22.4%, median age 62 years, median MELD 15), any degree of volume overload occurred in 51.3% and severe overload in 22.4% after albumin infusion. The median right ventricular-right atrial gradient (RVRA) was 23 mmHg (interquartile range [IQR] 20-28), while cirrhotic cardiomyopathy (CCM) was present in 15.8% (12/76) and diastolic dysfunction (DD ≥ Grade 1) in 36.1% (26/76). In multivariable analyses, higher RVRA levels were independently associated with any volume overload (odds ratio [OR] 1.83 per 5 mmHg increase, 95% confidence interval [CI] 1.09–3.10; p=0.023). This was further supported by a threshold analysis, showing that RVRA ≥ 25 mmHg significantly increased the risk of any volume overload (OR 4.30, 95%CI 1.21-15.31; p=0.024). Sensitivity analyses restricted to individual patients (n=54) confirmed these findings. Regarding clinical outcomes, we only included the first examination. High rates of liver-related events such as acute kidney injury (55.6%), spontaneous bacterial peritonitis (SBP; 22.2%), hepatic encephalopathy (HE; 29.6%) and mortality (29.6%) were observed within 6 months from baseline. In multivariable models, DD was associated with SBP at 3 months (OR 20.78, 95%CI 1.76–245.30; p=0.016). Furthermore, CCM according to the 2019 CCM consortium definitions was significantly associated with HE at 3 months (OR 6.12, 95%CI 1.30–28.72; p=0.022), but this effect did not persist until 6 months from baseline.

Conclusion

This study provides initial evidence of an association between RVRA and volume overload following albumin therapy, potentially reflecting an increased susceptibility to fluid challenge in conditions associated with subclinically elevated pulmonary arterial pressure in patients with decompensated cirrhosis. Although transient associations were observed between TTE parameters and liver-related outcomes, these findings require confirmation. Furthermore, clinically inapparent DD and CCM are a common finding in this population, while their prognostic role deserves further exploration in larger prospective cohort studies.

Disclosure

FB and SdM have nothing to declare. DS reports travelling fees from GIlead and Falk. AB serves as consultant and/or speaker for Boehringer Ingelheim, GE HealthCare; Hologic; W. L. Gore & Associates. JB was a consultant for AstraZeneca, NovoNordisk, Boehringer Ingelheim and Resolution Therapeutics.

Event

UEG Week Barcelona 2026

Topics

Mechanisms & Personalised Medicine Radiology & Imaging Hepatobiliary

Submission format

Abstract

Session

Liver cirrhosis: A cirrhotic conundrum - Diagnosis and evaluation

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

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ASSOCIATIONS BETWEEN DIASTOLIC AND SYSTOLIC DYSFUNCTION, VALVULAR HEART DISEASE, AND CIRRHOTIC CARDIOMYOPATHY WITH INTRAVASCULAR VOLUME OVERLOAD AFTER ALBUMIN INFUSION IN PATIENTS WITH LIVER CIRRHOSIS

Annalisa Berzigotti

Management of gastric metaplasia: Be aware of autoimmune gastritis

Judith Honing

LOW RECURRENCE RATES AFTER ENDOSCOPIC ERADICATION THERAPY OF BARRETT'S NEOPLASIA: LONG-TERM FOLLOW-UP RESULTS FROM THE NATIONWIDE DUTCH BARRETT'S REGISTRY

Roos E. Pouw

Large language model use for gastroenterology: Should we use it already, or is it too early given regulation and lacking data?

Omer Ahmad

STENOVA TRIAL UPDATE: OPEN-LABEL EXTENSION OF ONTUNISERTIB IN FIBROSTENOSING CROHN’S DISEASE WITH OBJECTIVE IMAGING EFFICACY ASSESSMENTS

Philippe Wiesel

SARCOPENIA AS AN INDEPENDENT DOMAIN IN CIRRHOSIS: ASSOCIATION WITH DISEASE SEVERITY AND SEX-SPECIFIC DIFFERENCES

Gagik Hakobyan

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Management of gastric metaplasia: Be aware of autoimmune gastritis

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Management of gastric metaplasia: Be aware of autoimmune gastritis

Judith Honing 1

Affiliations

1 Erasmus Medical Center Rotterdam, Rotterdam, Netherlands

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Abstract

Event

Postgraduate Teaching Programme Barcelona 2026

Topics

Stomach & H. Pylori

Session

H. pylori and precancerous conditions

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

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ASSOCIATIONS BETWEEN DIASTOLIC AND SYSTOLIC DYSFUNCTION, VALVULAR HEART DISEASE, AND CIRRHOTIC CARDIOMYOPATHY WITH INTRAVASCULAR VOLUME OVERLOAD AFTER ALBUMIN INFUSION IN PATIENTS WITH LIVER CIRRHOSIS

Annalisa Berzigotti

Management of gastric metaplasia: Be aware of autoimmune gastritis

Judith Honing

LOW RECURRENCE RATES AFTER ENDOSCOPIC ERADICATION THERAPY OF BARRETT'S NEOPLASIA: LONG-TERM FOLLOW-UP RESULTS FROM THE NATIONWIDE DUTCH BARRETT'S REGISTRY

Roos E. Pouw

Large language model use for gastroenterology: Should we use it already, or is it too early given regulation and lacking data?

Omer Ahmad

STENOVA TRIAL UPDATE: OPEN-LABEL EXTENSION OF ONTUNISERTIB IN FIBROSTENOSING CROHN’S DISEASE WITH OBJECTIVE IMAGING EFFICACY ASSESSMENTS

Philippe Wiesel

SARCOPENIA AS AN INDEPENDENT DOMAIN IN CIRRHOSIS: ASSOCIATION WITH DISEASE SEVERITY AND SEX-SPECIFIC DIFFERENCES

Gagik Hakobyan

UEG Presentation

New

Share via Email Share on Facebook Share on X Share on LinkedIn Share on Bluesky

LOW RECURRENCE RATES AFTER ENDOSCOPIC ERADICATION THERAPY OF BARRETT'S NEOPLASIA: LONG-TERM FOLLOW-UP RESULTS FROM THE NATIONWIDE DUTCH BARRETT'S REGISTRY

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LOW RECURRENCE RATES AFTER ENDOSCOPIC ERADICATION THERAPY OF BARRETT'S NEOPLASIA: LONG-TERM FOLLOW-UP RESULTS FROM THE NATIONWIDE DUTCH BARRETT'S REGISTRY

Vincent Bos 1, Sanne van Munster 1, Bas L.A.M. Weusten 2,3, Lorenza Alvarez Herrero 2, Erik Jan Schoon 4, Wouter L. Curvers 4, Wouter B. Nagengast 5, Alaa Alkhalaf 6, Arjun D. Koch 7, Pieter Jan de Jonge 7, Jessie Westerhof 5, Martin Houben 8, Jacques J. Bergman 1, Roos E. Pouw 3

Affiliations

1 Amsterdam UMC, Amsterdam, Netherlands

2 St Antonius Hospital, Nieuwegein, Netherlands

3 UMC Utrecht, Utrecht, Netherlands

4 Catharina Hospital, Eindhoven, Netherlands

5 University Medical Center Groningen, Groningen, Netherlands

6 Isala, Zwolle, Netherlands

7 Erasmus MC - University Medical center, Rotterdam, Netherlands

8 Haga Teaching Hospital, The Hague, Netherlands

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Abstract

Introduction

Endoscopic eradication therapy (EET) with radiofrequency ablation (RFA) ± endoscopic resection (ER) is recommended for Barrett’s esophagus (BE) with early neoplasia¹. After successful EET, the advised endoscopic follow-up (FU) duration is 5 years for low-grade dysplasia (LGD) and 10 years for high-grade dysplasia (HGD)/T1 esophageal adenocarcinoma (EAC)¹. These recommendations are mostly based on expert opinion, as high-quality long-term FU data is scarce.

Aims & Methods

We aimed to evaluate long-term outcomes and identify predictors of recurrent advanced EAC in a nationwide BE treatment cohort. We included all patients with successful EET between 2008-2018 in the Netherlands, in line with our previous publication², with additional FU data collected until September 2025. Endoscopic FU was defined as time from last treatment to last FU endoscopy. Vital FU was defined as time from last treatment to vital status assessment or death. Primary outcome was recurrent dysplasia/EAC. A Cox proportional hazards regression was performed to identify independent predictors of advanced EAC, defined as EAC exceeding boundaries of curative endoscopic treatment. Variables were selected based on clinical plausibility and included parameters available at baseline assessment, treatment, and FU.

Results

We included 1269 patients (1038 male, median age 66 years, median BE C2M4) with baseline LGD in 27%, and HGD/low-risk EAC in 73%. The overall median endoscopic FU was 65 months (IQR 42-93) since the last treatment with a median 5 endoscopies (IQR 3-7), and median 78 months (54-107) since baseline. In 145/1269 patients (11%), endoscopic FU was ≥ 10 years and 454/1269 (36%) started endoscopic FU in a non-BEC a median 16 months (6-30) since last treatment. Endoscopic FU was stopped in 58% following guideline recommendation to stop (20%), limited life expectancy (18%), unrelated death (14%), or lost to FU (4%).
Recurrence of dysplasia/EAC was detected in 91/1269 (7%; annual risk 1.3% [95% CI 1.1-1.6]). Seventy-three endoscopies were needed to find one recurrence. Overall, 76/91 (84%) recurrences were amenable for endoscopic treatment (LGD n=38; HGD/T1 EAC n = 38). The remaining 15/91 ((16%, 1% of total cohort (n=15/1269)) progressed to advanced EAC. Of these, 8/15 underwent treatment with curative intent, 1/15 was referred for treatment, and 6/15 were ineligible or declined curative treatment. EAC-related death occurred in 11/1269 (0.9%). Median FU from last normal endoscopy until advanced EAC was 16 months (IQR 7-38).
Most recurrences were detected during routine FU endoscopy (90%; n=82/91), while 10% (9/91) was diagnosed in an extra endoscopy performed due to symptoms. In 6/1269 (0.5%) patients, recurrent HGD/EAC, including 4 advanced EAC, were diagnosed a median 12 months (IQR 6-61) after the guideline-recommended time point at which FU could have been stopped. However, endoscopic FU had actually been stopped in only 1/6 of these patients. Overall, during a median vital FU of 101 months (IQR 80-136), 319/1269 (25%) patients had unrelated death.
For advanced EAC recurrence, an increasing number of ER sessions and longer BE length were independently associated with an increased risk.

All patients N=1269	FU time, months / FU endoscopies, n, median (IQR)	LGD in normal GEJ w/o BE, n (% [95%CI])	FU until LGD in normal GEJ w/o BE, months, median (IQR; annual risk)	Dysplasia/EAC in recurrent BE, n (% [95%CI])	FU until Dysplasia/EAC in recurrent BE, months, median (IQR; annual risk)	Advanced EAC, n (% [95%CI])	FU until Advanced EAC, months, median (IQR; annual risk)	EAC-related death, n (% [95%CI])	Non-EAC-related death, n (% [95%CI])
Baseline LGD (n=347)	65 (47-83) / 5 (4-6)	5 (5% [1-3])	31 (19-51; 0.2%)	11 (3% [2-6])	43 (30-56; 0.4%)	3 (1% [0-3])	85 (N/A; 0.1%)	2 (1% [0-2])	47 (14% [10-18])
Baseline HGD/EAC (n=922)	65 (40-99) / 5 (3-7)	13 (1% [0-2])	28 (17-46; 0.2%)	47 (5% [4-7])	34 (24-54; 0.6%)	12 (1% [0-2])	34 (17-90; 0.2%)	9 (1% [0-1])	272 (30% [27-33])
BE: Barrett’s esophagus; EAC: esophageal adenocarcinoma; FU: follow-up; HGD: high-grade dysplasia; IQR: interquartile range; LGD: low-grade dysplasia;

Conclusion

This largest cohort to date with long-term endoscopic FU after EET in an expert setting shows low recurrence risk, with EAC-related mortality (<1%), and unrelated mortality of 25%.

References

1. Weusten BLAM, Bisschops R, Dinis-Ribeiro M, et al. Diagnosis and management of Barrett esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2023;55(12):1124-1146. doi:10.1055/a-2176-24
2. Van Munster S, Nieuwenhuis E, Weusten BLAM, et al. Long-term outcomes after endoscopic treatment for Barrett's neoplasia with radiofrequency ablation ± endoscopic resection: results from the national Dutch database in a 10-year period. Gut. 2022;71(2):265-276. doi:10.1136/gutjnl-2020-322615

Event

UEG Week Barcelona 2026

Topics

Oesophagus Histopathology Endoscopy Digestive Oncology

Submission format

Abstract

Session

Interventional endoscopy: What's new and cool!

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

ASSOCIATIONS BETWEEN DIASTOLIC AND SYSTOLIC DYSFUNCTION, VALVULAR HEART DISEASE, AND CIRRHOTIC CARDIOMYOPATHY WITH INTRAVASCULAR VOLUME OVERLOAD AFTER ALBUMIN INFUSION IN PATIENTS WITH LIVER CIRRHOSIS

Annalisa Berzigotti

Management of gastric metaplasia: Be aware of autoimmune gastritis

Judith Honing

LOW RECURRENCE RATES AFTER ENDOSCOPIC ERADICATION THERAPY OF BARRETT'S NEOPLASIA: LONG-TERM FOLLOW-UP RESULTS FROM THE NATIONWIDE DUTCH BARRETT'S REGISTRY

Roos E. Pouw

Large language model use for gastroenterology: Should we use it already, or is it too early given regulation and lacking data?

Omer Ahmad

STENOVA TRIAL UPDATE: OPEN-LABEL EXTENSION OF ONTUNISERTIB IN FIBROSTENOSING CROHN’S DISEASE WITH OBJECTIVE IMAGING EFFICACY ASSESSMENTS

Philippe Wiesel

SARCOPENIA AS AN INDEPENDENT DOMAIN IN CIRRHOSIS: ASSOCIATION WITH DISEASE SEVERITY AND SEX-SPECIFIC DIFFERENCES

Gagik Hakobyan

UEG Presentation

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Large language model use for gastroenterology: Should we use it already, or is it too early given regulation and lacking data?

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Large language model use for gastroenterology: Should we use it already, or is it too early given regulation and lacking data?

Marcello Fabio Maida 1, Omer Ahmad 2

Affiliations

1 Department of Medicine and Surgery, University of Enna ‘Kore’, Enna, Italy

2 University College London, London, United Kingdom

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Abstract

Event

Postgraduate Teaching Programme Barcelona 2026

Session

AI integration in my clinical practice today

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

ASSOCIATIONS BETWEEN DIASTOLIC AND SYSTOLIC DYSFUNCTION, VALVULAR HEART DISEASE, AND CIRRHOTIC CARDIOMYOPATHY WITH INTRAVASCULAR VOLUME OVERLOAD AFTER ALBUMIN INFUSION IN PATIENTS WITH LIVER CIRRHOSIS

Annalisa Berzigotti

Management of gastric metaplasia: Be aware of autoimmune gastritis

Judith Honing

LOW RECURRENCE RATES AFTER ENDOSCOPIC ERADICATION THERAPY OF BARRETT'S NEOPLASIA: LONG-TERM FOLLOW-UP RESULTS FROM THE NATIONWIDE DUTCH BARRETT'S REGISTRY

Roos E. Pouw

Large language model use for gastroenterology: Should we use it already, or is it too early given regulation and lacking data?

Omer Ahmad

STENOVA TRIAL UPDATE: OPEN-LABEL EXTENSION OF ONTUNISERTIB IN FIBROSTENOSING CROHN’S DISEASE WITH OBJECTIVE IMAGING EFFICACY ASSESSMENTS

Philippe Wiesel

SARCOPENIA AS AN INDEPENDENT DOMAIN IN CIRRHOSIS: ASSOCIATION WITH DISEASE SEVERITY AND SEX-SPECIFIC DIFFERENCES

Gagik Hakobyan

UEG Presentation

New

Share via Email Share on Facebook Share on X Share on LinkedIn Share on Bluesky

STENOVA TRIAL UPDATE: OPEN-LABEL EXTENSION OF ONTUNISERTIB IN FIBROSTENOSING CROHN’S DISEASE WITH OBJECTIVE IMAGING EFFICACY ASSESSMENTS

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STENOVA TRIAL UPDATE: OPEN-LABEL EXTENSION OF ONTUNISERTIB IN FIBROSTENOSING CROHN’S DISEASE WITH OBJECTIVE IMAGING EFFICACY ASSESSMENTS

Florian Rieder 1, Cathy Lu 2, Anja Poulsen 3, Walter Reinisch 4, Jaroslaw Kierkus 5, Elena Ricart 6, Joel Flechter 7, Jordi Rimola 8, Pieter-Jan Stiers 9, Kim Thys 9, Margreke Brill 9, Silke Hüttner 9, Rolf Van Heeswijk 9, Andrea Saez 10, Tim Van Kaem 9, Philippe Wiesel 11

Affiliations

1 Cleveland Clinic Foundation, Cleveland Heights, United States

2 University Of Calgary, Calgary, Canada

3 Rigshospitalet, Copenhagen Ø, Denmark

4 Medical University of Vienna, Wien, Austria

5 Children’s Memorial Health Institute, Warsaw, Poland

6 Hospital Clinic, Barcelona, Spain

7 Mayo Clinic, Rochester, United States

8 Hospital Clínic Barcelona, Barcelona, Spain

9 Agomab Therapeutics NV, Berchem, Belgium

10 Agomab Spain S.L.U., A Coruña, Spain

11 Agomab US, Cambridge, United States

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Abstract

Introduction

Ontunisertib is an oral GI-restricted ALK5 inhibitor blocking the TGFβ pathway, and is in development for treatment of fibrostenosing Crohn's disease (FSCD). A challenge in developing FSCD therapies is the lack of validated objective endpoints. STENOVA is a randomized trial conducted in FSCD. We present imaging results of the 12-week placebo-controlled Part A and an update on the ongoing open-label treatment extension (OLE; Part B; preliminary data).

Aims & Methods

Adults with symptomatic FSCD with at least 1 MRE-confirmed ileal stricture were randomized to receive ontunisertib 200mg BID, 100mg QD, or placebo (PBO) for 12 weeks in Part A. Participants completing Part A could receive ontunisertib 200mg BID for up to 48 weeks in Part B (launched during Part A). In Part A, ileocolonoscopy and MRE were performed at baseline and Week 12. In Part B OLE, ileocolonoscopy is planned at Week 48 and MRE at Weeks 24 and 48. Both are centrally evaluated, using SES-CD and stricture-related items, respectively.

Results

Part A included 103 participants (34/34/35 in the 200mg/100mg/PBO groups), 92 completed treatment. In total, 49 participants were included in Part B OLE (16/19/14 from the 200mg/100mg/PBO groups of Part A, 94% of eligible participants). At the analysis cut-off date, 44 participants were ongoing and 24 completed the first 24 weeks of OLE treatment.
Part A achieved its primary endpoint, with ontunisertib for 12 weeks being generally well tolerated. Data from Part B until the cut-off date supports the longer-term safety and tolerability profile of ontunisertib.
In Part A, an improvement in SES-CD was observed at Week 12 in the 200mg BID group. In this group, SES-CD showed higher endoscopic response and remission rate, and a higher proportion of participants with non-passable strictures at baseline had passable strictures at Week 12. The SES-CD, particularly the narrowing component, demonstrated robust inter-reader agreement. In the 200mg BID and 100mg QD groups, MRE items showed trends towards stricture improvement compared to PBO. This was most evident for stricture length, the item with the highest reliability and strongest correlation with overall disease severity.
Over the first 24-week period in Part B OLE, a continued trend for improvement in MRE stricture length was observed in participants originally randomized to ontunisertib. In participants who transitioned from PBO, the worsening stricture length observed in Part A ceased to progress and stabilized during Part B OLE.

Conclusion

Treatment with ontunisertib for up to 36 weeks was generally well tolerated. Positive trends in endoscopic and MRE outcomes were observed. The data suggest that ontunisertib has potential to be suitable for chronic dosing and may provide a therapeutic option for FSCD patients. These outcomes contribute to the FSCD field by advancing the validation of objective endpoints.

Disclosure

Tim Van Kaem, submitting author is an employee of Agomab Therapeutics.

Event

UEG Week Barcelona 2026

Topics

Mechanisms & Personalised Medicine IBD

Submission format

Abstract

Session

Looking into the future: Novel therapeutics in IBD (Part 2)

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

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ASSOCIATIONS BETWEEN DIASTOLIC AND SYSTOLIC DYSFUNCTION, VALVULAR HEART DISEASE, AND CIRRHOTIC CARDIOMYOPATHY WITH INTRAVASCULAR VOLUME OVERLOAD AFTER ALBUMIN INFUSION IN PATIENTS WITH LIVER CIRRHOSIS

Annalisa Berzigotti

Management of gastric metaplasia: Be aware of autoimmune gastritis

Judith Honing

LOW RECURRENCE RATES AFTER ENDOSCOPIC ERADICATION THERAPY OF BARRETT'S NEOPLASIA: LONG-TERM FOLLOW-UP RESULTS FROM THE NATIONWIDE DUTCH BARRETT'S REGISTRY

Roos E. Pouw

Large language model use for gastroenterology: Should we use it already, or is it too early given regulation and lacking data?

Omer Ahmad

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Philippe Wiesel

SARCOPENIA AS AN INDEPENDENT DOMAIN IN CIRRHOSIS: ASSOCIATION WITH DISEASE SEVERITY AND SEX-SPECIFIC DIFFERENCES

Gagik Hakobyan

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SARCOPENIA AS AN INDEPENDENT DOMAIN IN CIRRHOSIS: ASSOCIATION WITH DISEASE SEVERITY AND SEX-SPECIFIC DIFFERENCES

Anna Mkrtchyan 1, Amalya Mkhitaryan 1, Edmond Baghdasaryan 2, Sofya Grigoryan 1, Yeva Manucharyan 2, Gohar Saroyan 1, Anna Abgaryan 2, Gagik Hakobyan 1

Affiliations

1 Mikayelyan University Hospital, Yerevan, Armenia

2 Yerevan State Medical University, Yerevan, Armenia

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Abstract

Introduction

Sarcopenia and frailty are important predictors of adverse outcomes in patients with liver cirrhosis, yet their assessment is often overlooked in routine clinical practice. The prevalence of sarcopenia in patients with cirrhosis varies across studies, ranging from approximately 40% to 70% and is associated with an increased mortality. Physical frailty, assessed using performance-based tests, further contributes to disease burden and clinical outcomes. This study aimed to evaluate the relationship between physical performance, cognitive function, and liver disease severity.

Aims & Methods

We conducted a cross-sectional study of 71 patients with liver cirrhosis of different etiologies between March 2025 and March 2026. Disease severity was assessed using the Child–Pugh classification and MELD 3.0 score. Sarcopenia and physical frailty were evaluated using bedside tests, including handgrip strength (HGS), the Timed Up and Go (TUG) test, and gait speed. Handgrip strength was used as the primary indicator of sarcopenia, as it is a validated marker of muscle function in cirrhosis. Low HGS was defined according to EWGSOP2 criteria (<27 kg in men and <16 kg in women), measured using the dominant hand. Cognitive function and minimal hepatic encephalopathy were screened using the animal naming test (threshold of 15 animals). Associations between variables were analyses using Spearman’s correlation and the Mann–Whitney U test. Exploratory logistic regression analysis was performed to assess factors associated with low HGS, adjusting for sex. Patients with hepatocellular carcinoma (HCC) or other malignancies were excluded.

Results

Among 71 patients, 42 (59.2%) were male and 29 (40.8%) were female. Overall, 60 (84.5%) patients had normal handgrip strength (HGS), while 11 (15.5%) had reduced HGS. Abnormal gait speed was observed in 44 (62.0%) patients, and 56 (78.9%) had abnormal Timed Up and Go (TUG) test results. The median MELD 3.0 score was 15 (IQR 11–18), and median HGS was 28.4 kg (IQR 19.4–37.2). Weak, non-significant correlations were observed between HGS and MELD score (ρ = −0.16, p = 0.18), as well as between HGS and Child–Pugh class (ρ = −0.02, p = 0.85). In sex-stratified analysis, a moderate negative correlation was observed between HGS and MELD score in male patients (ρ = −0.51, p < 0.001), as well as between HGS and Child–Pugh class (ρ = −0.40, p = 0.008). In contrast, no significant correlations were found in female patients (p > 0.05 for both comparisons). No significant difference in HGS was observed between patients who named ≥15 animals and those who named <15 animals (Mann–Whitney U = 725, p = 0.20). In exploratory logistic regression analysis adjusted for sex, higher MELD 3.0 score was associated with increased odds of reduced HGS (OR 1.14 per point increase, 95% CI 1.01–1.29, p = 0.039), whereas sex was not independently associated with low HGS (p = 0.876).

Conclusion

Sarcopenia, as assessed by HGS, showed no significant overall correlation with liver cirrhosis severity scores, including MELD and Child–Pugh classification, supporting the concept that muscle dysfunction represents a distinct clinical domain in cirrhosis. However, a clear sex-specific pattern was observed, with moderate inverse associations between handgrip strength and disease severity present in male patients but absent in females. These findings suggest that the relationship between liver disease severity and muscle strength may be modulated by sex-related factors and highlight the need for sex-specific assessment strategies in cirrhosis.

References

Endo K et al. Annual changes in grip strength and skeletal muscle mass in chronic liver disease: an observational study.
Ebadi M et al. Sarcopenia in cirrhosis: from pathogenesis to interventions.

Conference

UEG Week Barcelona 2026

Topics

Hepatobiliary

Submission format

Abstract

Session

LIVER (Posters)

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

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