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Symptomatic gallstones

Philip de Reuver 1

1 Radboudumc, Nijmegen, Netherlands

Event

UEG Week Berlin 2025

Topics

Colorectal Hepatobiliary Primary Care

Session

Cross-cutting: Management changes in high prevalence problems

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Diagnosis and treating sarcopenia in hepatic disorders

Francesca Romana Ponziani 1

1 Agostino Gemelli Hospital, Rome, Italy

Event

UEG Week Berlin 2025

Topics

Hepatobiliary

Session

What's new in complications in chronic liver disease in 2025?

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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... for medical therapy in colorectal cancer

Sebastian Foersch 1

1 University Medical Center Mainz, Mainz, Germany

Event

UEG Week Berlin 2025

Topics

Colorectal IBD Surgery

Session

Predicting patient outcomes...

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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PLASMA PROTEOMIC PROFILES FOR PREDICTING HEPATIC COMPLICATIONS UP TO 16 YEARS BEFORE ONSET

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Introduction

Chronic liver disease is a major global health concerns, contributing to over 1.4 million annual deaths worldwide¹. Its primary fatal outcomes, hepatic complications^2,3, arise from liver cirrhosis, hepatocellular carcinoma and hepatic decompensation. The early, reversible stages of chronic liver disease are frequently asymptomatic and overlooked, leading to delayed diagnoses and irreversible complications that treatment options are limited.^4,5. Therefore, reliable tools to identify whether a person will develop hepatic complications in the future have become a public health priority, enabling early diagnosis and timely intervention in high-risk populations.

Aims & Methods

This study aimed to employ machine learning to develop proteomics-based models for the early identification of hepatic complications. In this study, 37,178 adults without hepatic complications at baseline were analyzed from a prospective cohort from United Kingdom, with plasma levels of 2,736 proteins measured using Olink technology. Cox regression was used to identify significant proteins associated with incident hepatic complications. Models based on importance-top-ranking proteins were constructed using LightGBM learners of Automated Machine Learning (AutoML) and internal validated through 5-fold cross validation in the derivation set (n = 37,178). Independent validation was then conducted in a geographically distinct UKB cohort (n = 15,767).

Results

Over a median follow-up of 13.8 years, 338 participants developed hepatic complications. Cox regression identified 593 proteins significantly associated with incident hepatic complications. Among them, GDF15, PROC, GGT1, ANXA10, IL18, MFAP4, COL4A1, CDCP1 and IL6 were ranked highest in protein importance ordering. The protein model showed a considerable predictive accuracy for hepatic complications under different time scenarios in the UKB validation set: all-year (area under the curve [AUC] = 0.89), within 5 years (AUC = 0.88), within 10 years (AUC = 0.91), over 10 years (AUC = 0.81), and achieved superior predictive performance compared to models with demographic predictors, laboratory indicators, polygenic risk score (PRS) and traditional risk score models (Protein 0.89 vs. Demographics 0.83, Laboratory 0.85, PRS 0.49; Fibrosis-4 index [FIB-4] 0.76, Aspartate aminotransferase to platelet ratio index [APRI] 0.78; all P < 0.05). Combined with clinical data and PRS, the predictor performance is further enhanced: all-year (AUC = 0.91), within 5 years (AUC = 0.91), within 10 years (AUC = 0.90), over 10 years (AUC = 0.83). Individuals in the high-risk group stratified by the protein model were 16.27 times more likely to develop hepatic complications.

Conclusion

Our study constructed a novel protein model for hepatic complications risk stratification and could be used to predict individuals who will develop hepatic complications up to 16 years in advance in the general population.

References

1. Tham EKJ, Tan DJH, Danpanichkul P, et al. The Global Burden of Cirrhosis and Other Chronic Liver Diseases in 2021. Liver Int 2025;45:e70001.
2. Åberg F, Asteljoki J, Männistö V, et al. Combined use of the CLivD score and FIB-4 for prediction of liver-related outcomes in the population. Hepatol Baltim Md 2024;80:163–172.
3. Innes H, Morling JR, Buch S, et al. Performance of routine risk scores for predicting cirrhosis-related morbidity in the community. J Hepatol 2022;77:365–376.
4. Karlsen TH, Sheron N, Zelber-Sagi S, et al. The EASL–Lancet Liver Commission: protecting the next generation of Europeans against liver disease complications and premature mortality. The Lancet 2022;399:61–116.
5. Serra-Burriel M, Juanola A, Serra-Burriel F, et al. Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: a multicohort study. Lancet Lond Engl 2023;402:988–996.

PLASMA PROTEOMIC PROFILES FOR PREDICTING HEPATIC COMPLICATIONS UP TO 16 YEARS BEFORE ONSET

Shuo Chen 1, Jing Feng 1, Yajie Zhang 1, Tong Lin 1, Wuzheng Xia 2, Weihong Sha 1, Hao Chen 1

1 Department of Gastroenterology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China

2 Department of Organ transplantation, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China

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

UEG Presentation

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PRECISION-CUT INTESTINAL SLICES PROVIDE EX VIVO ASSESSMENT OF REGION-SPECIFIC IMMUNE RESPONSES AND EFFICACY OF FILGOTINIB IN CROHN'S DISEASE

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Introduction

Inflammatory bowel disease (IBD) is a growing global health problem with increasing prevalence. Current therapeutic strategies for IBD are mainly aimed at modulating the dysregulated immune activity in the intestinal mucosa. Targeting the JAK/STAT signalling pathway has been shown to be highly effective in ulcerative colitis, but not in Crohn's disease (CD), where efficacy was found to be insufficient in the initiation phase of a clinical trial [1]. Failure of the therapeutic response in Crohn’s disease may be influenced by the unique immune microenvironments in the small and large intestine and their characteristic cytokine profiles and immune cell compositions.

Aims & Methods

To gain deeper insight into region-specific efficacy in the inflamed ileum versus colon, this study investigates the immunomodulatory effects of filgotinib, a Jak1 inhibitor, using precision-cut intestinal slices (PCIS) from patients with Crohn's diseases. PCIS are viable, ultra-thin human tissue slices that retain the original intestinal architecture ex vivo and contain important cell types, including resident immune cells.
PCIS were prepared from resected ileal and colonic tissue of CD patients. The slices were cultured ex vivo and stimulated with concanavalin A or anti-CD3/CD28 antibodies to induce T cell-driven inflammatory responses. Filgotinib (1-100 µM) was applied to assess the immunomodulatory effects of JAK1 inhibition following Concanavalin A preactivation. To exclude treatment-related toxicity, cellular integrity was evaluated using an LDH release assay. Tissue morphology was examined by H&E staining and immunofluorescence. The immune response was assessed by multiplex ELISA of 20 cytokines.

Results

After filgotinib treatment, primary tissue slices from the ileum and colon of CD patients remained viable. Regional morphological characteristics of ileum and colon tissue were preserved after ex vivo cultivation, with prominent villi and smaller crypts in the ileum, and larger, more frequent crypts and flattened villi in the colon. Compared to non-CD tissue slices, Crohn’s disease-related changes, such as immune cell accumulation, were also observed in CD tissue slices ex vivo. Upon T cell-specific stimulation with anti-CD3/CD28 antibodies, region-specific immune reactivity was observed. Colonic PCIS showed an increased release of IL-2 (~3-fold), IL-10 (~2‑fold) and TRAIL (~4-fold) compared to ileal PCIS, indicating a stronger involvement of Th and regulatory T cells in the colon. In contrast, ileal PCIS showed higher levels of MIP-3α (2-fold) and granzyme A (~8-fold) after stimulation, suggesting increased cytotoxic T cell activity in this region. Filgotinib treatment showed region-specific differences in its ability to modulate cytokine release in PCIS of CD patients. In colonic PCIS, filgotinib reduced the induced secretion of Th17-associated cytokines such as IL-17F and IL-22 by up to 95%, whereas in ileal PCIS it showed no effect on the same cytokines.

Conclusion

In conclusion, filgotinib exhibited more potent anti‑inflammatory effect on Th17 cells in the colon, and a markedly reduced efficacy in the ileum. This study demonstrates for the first time that precision-cut intestinal slices can be used to predict region-specific drug response in inflamed intestinal tissue ex vivo, underscoring the critical importance of region-specific immune profiling in IBD and highlight the limited efficacy of JAK1 inhibition in ileum. This ex vivo, patient-derived model represents a valuable platform for evaluating localised treatment efficacy and advancing personalised therapeutic strategies in IBD.