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A RANDOMIZED CONTROLLED TRIAL TO STUDY THE EFFECT OF PROTON PUMP INHIBITORS ON RECURRENT BLEEDING EPISODES AND MORTALITY AFTER ENDOSCOPIC VARICEAL LIGATION FOR ACUTE VARICEAL BLEEDING IN PATIENTS OF LIVER CIRRHOSIS

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Introduction

Acute variceal bleeding is a life-threatening decompensating event in the natural history of cirrhosis. Endoscopic variceal ligation (EVL) along with non-selective beta blockers or carvedilol are current standard of care for patients with acute esophageal variceal bleeding. Use of proton pump inhibitors (PPI) in post EVL period is more of a personal choice as various society guidelines do not recommend continuation of PPI after EVL owing to low quality of evidence to support their use. The literature regarding the benefits of PPI in post EVL re-bleeding and mortality is heterogeneous without any clear answer particularly for mortality.

Aims & Methods

We conducted a single centre, outcome assessor blinded prospective randomized control trial where patients of liver cirrhosis with suspected or documented acute variceal bleeding were screened and those who underwent EVL were randomized into PPI or No-PPI group. Patients in the PPI group received Tab esomeprazole 40 mg once a day in addition to standard of care for all the patients. Both groups were followed up at 2 weeks post index EVL after randomization for occurrence of rebleeding and a repeat upper gastrointestinal endoscopy (UGIE) to document presence or absence of post EVL ulcers, their number and size. All patients were again followed up at 3 months for development of recurrent bleeding, mortality and adverse effect like pain and dysphagia post EVL. Primary outcome was to compare the rate of recurrent bleeding after EVL between the 2 groups. Secondary outcomes were to assess the difference in mortality, number and size of post EVL ulcers and adverse effects in the form of pain and dysphagia post EVL. Association between categorical outcomes was assessed by cross tabulation and comparison of percentages. Chi square test was used to test statistical significance. The association between quantitative variables was assessed by independent sample t-test to assess statistical significance. A p value of <0.05 was considered significant.

Results

A total of 246 patients were screened from June 2023 to April 2024 and 170 patients were randomized to both the groups. Baseline parameters were comparable between the groups. In the primary outcome, number of patients who developed recurrent bleeding episode were 23 (28.05%) in the no-PPI group, which were significantly more in comparison to 9 (11.54%) in the PPI group (p=0.009). Among the secondary outcomes, incidence of mortality was higher in the no-PPI group [16 (19.51%) vs 13 (16.67%) respectively], although statistically non-significant (p=0.640). All 16 (100%) deaths in the no-PPI group were related to rebleeding episode in comparison to only 5 (38.46%) deaths in the PPI group (p=0.035). Incidence of post EVL ulcers was significantly more in the no-PPI group [65 (86.67%) vs 22 (30.99%) respectively; p<0.001]. Median post EVL ulcer number and size were also significantly higher in the no-PPI group [1 (IQR 1,2) vs 0 (IQR 0,1) (p=<0.001); 6 mm (IQR 5,8) vs 5 mm (IQR 5,6) (p=0.0061) respectively]. At 2 weeks, chest pain was reported by 7 (9.33%) patients in the no PPI group vs 2 (2.82%) patients in the PPI group (p=0.167). No patient reported dysphagia at 2 weeks. No patient reported chest pain or dysphagia at 3 months.

Conclusion

Prescription of PPI after EVL in patients of liver cirrhosis with acute esophageal variceal bleeding is beneficial as it significantly decreases the recurrent bleeding episodes as well as mortality in such patients.

A RANDOMIZED CONTROLLED TRIAL TO STUDY THE EFFECT OF PROTON PUMP INHIBITORS ON RECURRENT BLEEDING EPISODES AND MORTALITY AFTER ENDOSCOPIC VARICEAL LIGATION FOR ACUTE VARICEAL BLEEDING IN PATIENTS OF LIVER CIRRHOSIS

Harshal Mandavdhare 1, ABHISHEK YADAV 1, Vishal Sharma 1, Jimil Shah 1, Atul Saroch 1, VANEET JEARTH 1, Jayanta Samanta 1, Anupam Kumar Singh 1, Saroj Kant Sinha 1

1 Post Graduate Institute Of Medical Education And Research, Chandigarh, Chandigarh, India

Event

UEG Week Berlin 2025

Topics

Endoscopy Oesophagus

Submission format

Abstract

Session

Randomised controlled trials in upper GI endoscopy

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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How to approach the patient?

Marine Camus 1

1 Sorbonne University, Saint Antoine Hospital, Paris, France

Event

UEG Week Berlin 2025

Topics

Endoscopy Nurses Radiology & Imaging Surgery

Session

Non-variceal bleeding: Planning an emergency

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Panel discussion: Easily overlooked cases of chronic diarrhoea

Event

UEG Postgraduate Teaching Programme Berlin 2025

Topics

Primary Care

Session

Easily overlooked cases of chronic diarrhoea

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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A synergistic approach in short bowel syndrome: Nutrition and medical therapy

alison culkin 1, Simon Gabe 2

1 Northwick Park and St Mark's Hospital, Harrow, United Kingdom

2 St. Mark's Hospital, Harrow, United Kingdom

Event

UEG Postgraduate Teaching Programme Berlin 2025

Session

Untangling malabsorption in dysmotility and short bowel syndrome

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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"Please put a stop to my watery stools!"

Gian Eugenio Tontini 1

1 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

Event

UEG Postgraduate Teaching Programme Berlin 2025

Topics

Primary Care

Session

Easily overlooked cases of chronic diarrhoea

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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RADIOLOGICAL REMISSION IN PERIANAL FISTULIZING CROHN’S DISEASE: BASELINE MRI PREDICTORS AND IMPACT ON CLINICAL OUTCOMES

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Introduction

Deep remission in complex perianal fistulizing Crohn’s disease (PFCD) is defined by both clinical and radiological remission. As the ultimate therapeutic goal for this condition, deep remission requires thorough assessment. MRI is the gold standard for evaluating complex perianal involvement.

Aims & Methods

Our aim was to identify baseline MRI factors linked to deep remission in PFCD and assess its impact on clinical outcomes. All patients with complex PFCD treated with anti-TNF-α agents at the gastroenterology department underwent baseline MRI and clinical evaluation. Radiological assessment included the number and type of fistula tracts (per Parks classification), presence/size of pelvic collections, horseshoe tracts (encircling more than 75% of the anal circumference), and rectal wall thickening. The Van Assche score was calculated. Follow-up MRIs were obtained only after clinical remission to assess radiological remission.

Results

Out of 105 patients, 80 were included in the study (male-to-female ratio: 1.33), with a mean age of 32.35 years. On average, patients had 1.7 fistula tracts (range: 1–6), with trans-sphincteric fistulas accounting for 65% of cases. Specific subtypes included ano-vulvar tracts in 8 women (9.5%), rectovaginal in 5 patients (6%), and anorectal tracts extending to the scrotum in 2 men (2.4%). Pelvic collections were present in 14 individuals (16.7%), averaging 23.8 mm in size. Horseshoe-shaped tracts were identified in 19 patients (22.6%), and rectal wall thickening greater than 3 mm was seen in 49 (58.3%). The mean Van Assche MRI score was 14.9. All patients underwent seton placement. The majority (88.1%) received infliximab, while the remainder were treated with adalimumab. Clinical remission was achieved after a mean of 5.8 months. Radiological remission occurred in 24 patients (28.6%). Presence of horseshoe tracts (p=0.013) and Van Assche scores more than 14 (p=0.027) were significantly associated with failure to reach radiological remission. These factors were confirmed as independent predictors by multivariate analysis. Among those who initially achieved radiological remission, 13 experienced recurrence during an average follow-up of 65.8 months. Radiological remission was associated with improved outcomes: recurrence-free survival rates were 81.3% at 1 year, 62.7% at 3 years, and 50.1% at 5 years, compared to 62.2%, 35.8%, and 23.2%, respectively, in patients with clinical remission but without radiological remission.

Conclusion

Deep remission was achieved in about one-third of PFCD patients following clinical remission. Horseshoe fistulas and Van Assche score more than 14 predict failure to reach this goal, correlating with worse long-term outcomes. These findings support the Top-Class classification designating such cases as unsuitable for curative repair, emphasizing symptom control instead.

RADIOLOGICAL REMISSION IN PERIANAL FISTULIZING CROHN’S DISEASE: BASELINE MRI PREDICTORS AND IMPACT ON CLINICAL OUTCOMES

Sarra Laabidi 1, Amal Ghamougui 1, DONIA GOUIAA 1, sahar chtioui 1, Nadia Ben Mustapha 1, Meriem Serghini Ep Ghachem 1, Asma Labidi 1, Monia Fekih 1

1 Rabta Hospital, Tunis, Tunisia

Event

UEG Week Berlin 2025

Topics

IBD

Submission format

Abstract

Session

Treatment of fistulas in Crohn's disease

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Presentation

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LEVERAGING SPATIAL MULTI-OMICS TO UNCOVER THE ROLE OF DUCTULAR REACTION IN THE PROGRESSION OF METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE

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Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease estimated to affect 38% of the global adult population. Activation of hepatic progenitor cells (HPCs) and concurrent proliferation of reactive bile ducts (collectively referred to as ductular reaction) have been associated with advanced MASLD, liver fibrosis, and damage, yet their exact role during disease progression remains unclear.

Aims & Methods

This study aimed to investigate the prognostic and biological relevance of ductular reaction in the progression of MASLD by using a multi-omics approach. In this study, a total of 251 patient samples were included. Spatially resolved multi-omics techniques were implemented to characterise the HPC niche in advanced MASLD using laser microdissection combined with high-throughput RNA sequencing (RNA-seq), nanoString CosMx molecular profiling, followed by Lunaphore COMET proteome multiplexing at single-cell resolution. Cell deconvolution by integrating single nucleus RNA-seq of MASH biopsy samples was implemented to determine cell of origin. Bulk RNA-seq analysis of 206 MASLD biopsy samples, stratified by HPC gene signatures, was used to examine differences in clinical parameters and genotype. Finally, clinico-pathological prognostic features of HPCs were assessed in baseline biopsies of MASLD patients with a follow-up biopsy at least one year apart.

Results

A high-throughput transcriptomics analysis of the HPC niche identified 3,282 differentially expressed genes enriched in pro-inflammatory cytokines (e.g. CXCL6, CCL19, CCL2, CCL5, CCL21, SPP1), inflammatory cell markers (e.g. CCR2, CD48, CD8a, CD96, CXCR3, S100A4), as well as antigen presenting genes. Spatial transcriptomics combined with integrated single nucleus RNA-seq uncovered distinct subsets of ductular reaction based on the expression of inflammatory markers SPP1+ and CCL2+. Notably, SPP1+CCL2- ductular reaction localised predominantly within the parenchyma and peri-portal region, while CCL2+SPP1- ductular reaction was confined mainly to the portal tract. Neighbourhood analysis highlighted antigen-presenting cells and IGHA1+IGHG1+ plasma cells in close proximity to ductular reaction. Spatial proteomics validation identified CD48 and HLA-DR-expressing macrophages as key immune cells of the HPC niche. Furthermore, the resulting HPC gene signature stratified transcriptomics data from 206 NAFLD biopsies into distinct clusters characterised by presence of steatohepatitis, high disease activity, fibrosis and AST levels. In a dual biopsy cohort, HPC presence in the parenchyma at baseline was significantly associated with progression of at least 1 fibrosis stage and was able to predict fibrosis progression in MASLD in a binary logistic regression model.

Conclusion

This study identified a pro-inflammatory role for HPCs in patients with MASLD. Furthermore, we showed the clinical relevance of using HPC signatures associated with disease activity and inflammation, as well as their ability to predict fibrosis progression in MASLD patients.

LEVERAGING SPATIAL MULTI-OMICS TO UNCOVER THE ROLE OF DUCTULAR REACTION IN THE PROGRESSION OF METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE

Dania El Abyad 1, Markus Bösch 1, Ramy Younes 2, Simon Cockell 3, Jeremy Palmer 3, Michele Vacca 4, Michael Allison 5, Vlad Ratziu 6, Jörn Schattenberg 7, Ann K. Daly 3, Elisabetta Bugianesi 8, Dina Tiniakos 9, Tania Roskams 1, Quentin Anstee 10, Olivier Govaere 11

1 KU Leuven, Leuven, Belgium

2 Newcastle University, Newcastle Upon Tyne, United Kingdom|||University of Turin, Turin, Italy|||Boehringer Ingelheim International, Ingelheim, Germany

3 Newcastle University, Newcastle Upon Tyne, United Kingdom

4 Wellcome-MRC Institute of Metabolic Science, Bari, Italy

5 Cambridge University NHS Foundation Trust, Cambridge, United Kingdom

6 Sorbonne University, Paris, France

7 Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes, Mainz, Germany

8 AOU Città della Salute e della Scienza University of Torino, Torino, Italy, Torino, Italy

9 Newcastle University, Newcastle Upon Tyne, United Kingdom|||National & Kapodistrian University of Athens, Athens, Greece

10 Newcastle University, Newcastle, United Kingdom

11 KU Leuven, Leuven, Belgium|||Newcastle University, Newcastle Upon Tyne, United Kingdom

Event

UEG Week Berlin 2025

Topics

Hepatobiliary IBD Mechanisms & Personalised Medicine

Submission format

Abstract

Session

Predicting and understanding early stages of advanced liver disease

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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