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IMPROVEMENT OF HEPATIC STEATOSIS AND REDUCTION IN CARDIOVASCULAR EVENT IN PATIENTS WITH DIABETES MELLITUS: A PROSPECTIVE STUDY

Oh Sang Kwon 1, Yoon Suk Lee 1, Seung Kak Shin 1, Doojin Kim 1, Kyoung Oh Kim 1, Kiyoung Lee 1, Young Sil Eom 1, Byung-Joon Kim 1, Yun Soo Kim 1, Ju Hyun Kim 1

Affiliations

1 Gachon University Gil Medical Center, Incheon, Korea, Republic of

Summary

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In a two-year prospective study of 277 patients with diabetes mellitus, marked reduction in hepatic steatosis measured by controlled attenuation parameter was associated with lower incidence of new cardiovascular disease events.

Among patients stratified by change in controlled attenuation parameter, new cardiovascular disease incidence was 0% in those with CAP reduction of ≤-40 dB/m, 2% in those with changes between -40 and +40 dB/m, and 9.5% in those with CAP increases of ≥+40 dB/m (p=0.037).
Six patients (3.2%) developed new cardiovascular events during the two-year follow-up period, comprising three cardiac events and three neurovascular events.
Patients whose CAP decreased (n=176) had higher baseline CAP (284±50 vs. 255±47 dB/m, p<0.001) and were older (58±12 vs. 55±12 years, p=0.012) than those whose CAP increased (n=101), with lower insulin use (5.1% vs. 12.9%, p=0.022) but no significant differences in other cardiovascular risk factors.
The authors conclude that CAP monitoring may be a valuable tool for assessing cardiovascular disease risk in patients with diabetes, though they acknowledge this was an observational study.

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Abstract

Introduction

Patients with diabetes mellitus (DM) are at an increased risk of developing cardiovascular disease (CVD). Hepatic steatosis is common among patients with DM, but its impact on CVD risk remains unclear.

Aims & Methods

This study aimed to prospectively assess the association between a reduction in hepatic steatosis and a lower risk of CVD in patients with DM.
A total of 323 patients with DM were prospectively enrolled from January 2022, after excluding those with viral hepatitis, overt cirrhosis, and cancer. Clinical measurements and CVD history were recorded. The following parameters were assessed: body weight (BW), body mass index (BMI), waist circumference (WC), laboratory data (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, platelet count, hemoglobin A1C, cholesterol, and triglycerides), presence of hypertension (HTN), dyslipidemia, alcohol consumption, smoking status, liver stiffness measurement (LSM by FibroScan®), and current anti-DM medications. Hepatic steatosis was quantified using the controlled attenuation parameter (CAP) measured by FibroScan® at baseline and after two years. CVD was defined as ischemic heart disease or ischemic/hemorrhagic stroke.

Results

A total of 277 patients completed the two-year follow-up and underwent repeat CAP assessment. The mean age was 57±12 years, and 56.3% were male. The baseline mean CAP was 274±18 dB/m. A history of CVD was present in 86 (31%) patients, while 6 (3.2%) developed new CVD events during follow-up. Among the new CVD cases, 3 were cardiac events, and 3 were neurovascular events. CAP scores decreased in 176 patients (d-CAP group) and increased in 101 patients (i-CAP group). The mean CAP change was -33±29 dB/m in the d-CAP group and +24±18 dB/m in the i-CAP group. The mean age was higher in the d-CAP group than in the i-CAP group (58±12 vs. 55±12 years, p=0.012). The baseline mean CAP was higher in the d-CAP group than in the i-CAP group (284±50 vs. 255±47 dB/m, p<0.001). There were no significant differences in male proportion (58% vs. 53.5%, p=0.468), BW (71±14 vs. 73±17 kg, p=0.258), BMI (26.1±4.2 vs. 27±4.9 kg/m², p=0.14), WC (89±10 vs. 90±12 cm, p=0.397), laboratory data, HTN (56.8% vs. 48.5%, p=0.182), dyslipidemia (66.5% vs. 64.4%, p=0.72), alcohol consumption (24.4% vs. 21.8%, p=0.616), smoking status (48.9% vs. 43.6%, p=0.395), or baseline LSM (6.9±3.8 vs. 6.9±3.5 kPa, p=0.988) between the two groups. The use of metformin (93.2% vs. 93.1%, p=0.972) and pioglitazone (2.3% vs. 2%, p=1.0) did not differ significantly, but insulin use was lower in the d-CAP group than in the i-CAP group (5.1% vs. 12.9%, p=0.022). When stratified by CAP change, the incidence of new CVD was 0% (0/55) in patients with CAP reduction of ≤-40 dB/m, 2% (4/201) in those with changes between -40 and +40 dB/m, and 9.5% (2/21) in those with CAP increases of ≥+40 dB/m (p=0.037).

Conclusion

Hepatic steatosis, as measured by CAP, can change dynamically in patients with DM. Although this was an observational study, a marked decrease in CAP score was associated with a lower risk of CVD in patients with DM. Therefore, CAP monitoring may be a valuable tool for assessing CVD risk. Efforts to reduce hepatic steatosis, as reflected by CAP reduction, may contribute to CVD prevention in this population.

Conference

UEG Week Berlin 2025

Topics

Hepatobiliary

Submission format

Abstract

Session

MetALD: Bridging science and clinical practice (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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THE PROGNOSTIC VALUE OF CHOLINE PET/CT IN THE INITIAL ASSESSMENT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA

Patrick Flamen

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Abstract

Event

UEG Week Berlin 2025

Session

Innovative approaches in liver disease management

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Patrick Flamen

UEG Presentation

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Personalising treatment: Tailoring to precision

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Personalising treatment: Tailoring to precision

Francesco Sclafani 1

Affiliations

1 Université libre de Bruxelles, Bruxelles, Belgium

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Abstract

Event

UEG Week Berlin 2025

Topics

Colorectal Digestive Oncology Mechanisms & Personalised Medicine

Session

Catching up with every day's practise in colorectal cancer treatment

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Panel Discussion

Personalising treatment: Tailoring to precision

Francesco Sclafani

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

Hao Chen

Anticipating the Nobel: Non-coding RNAs in diagnostics and therapy

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Subrata Ghosh

THE PROGNOSTIC VALUE OF CHOLINE PET/CT IN THE INITIAL ASSESSMENT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA

Patrick Flamen

UEG Presentation

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

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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

Affiliations

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

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Abstract

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.

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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Panel Discussion

Personalising treatment: Tailoring to precision

Francesco Sclafani

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

Hao Chen

Anticipating the Nobel: Non-coding RNAs in diagnostics and therapy

Alexander Link

NOVEL TRANSCRIPTIONAL SIGNATURE OF CIRCULATING MONOCYTES DEFINES RESPONSE TO ADVANCED THERAPIES IN INFLAMMATORY BOWEL DISEASE

Subrata Ghosh

THE PROGNOSTIC VALUE OF CHOLINE PET/CT IN THE INITIAL ASSESSMENT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA

Patrick Flamen

UEG Presentation

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

Anticipating the Nobel: Non-coding RNAs in diagnostics and therapy

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Anticipating the Nobel: Non-coding RNAs in diagnostics and therapy

Alexander Link 1

Affiliations

1 Otto-von-Guericke University of Magdeburg, Magdeburg, Germany

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Abstract

Event

UEG Week Berlin 2025

Topics

Mechanisms & Personalised Medicine

Session

The art of making clinical research precise: Biomarkers of the future - Is it liquid gold?

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

Panel Discussion

Personalising treatment: Tailoring to precision

Francesco Sclafani

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

Hao Chen

Anticipating the Nobel: Non-coding RNAs in diagnostics and therapy

Alexander Link

NOVEL TRANSCRIPTIONAL SIGNATURE OF CIRCULATING MONOCYTES DEFINES RESPONSE TO ADVANCED THERAPIES IN INFLAMMATORY BOWEL DISEASE

Subrata Ghosh

THE PROGNOSTIC VALUE OF CHOLINE PET/CT IN THE INITIAL ASSESSMENT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA

Patrick Flamen

UEG Presentation

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

NOVEL TRANSCRIPTIONAL SIGNATURE OF CIRCULATING MONOCYTES DEFINES RESPONSE TO ADVANCED THERAPIES IN INFLAMMATORY BOWEL DISEASE

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NOVEL TRANSCRIPTIONAL SIGNATURE OF CIRCULATING MONOCYTES DEFINES RESPONSE TO ADVANCED THERAPIES IN INFLAMMATORY BOWEL DISEASE

Asma Amamou 1, Cian O'Mahony 1, Jan Toman 1, Aida Lopez Espinar 2, Alan Deery 1, Piotr Kowalski 3, Marietta Iacucci 1, Subrata Ghosh 1

Affiliations

1 APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland

2 School of Pharmacy, University College Cork, Cork, Ireland

3 APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland|||School of Pharmacy, University College Cork, Cork, Ireland

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Abstract

Introduction

Treatment response in inflammatory bowel disease (IBD) is highly variable, with an urgent need for biomarkers to guide therapeutic decisions. Circulating monocytes, key players in intestinal immunity, act as precursors to tissue macrophages and contribute to inflammation and mucosal healing. The transcriptional programs that govern monocyte fate and their association with treatment outcomes remain poorly defined. Ikaros family proteins regulate gene expression through distinct mechanisms in lymphocytes, but little is known about their role in monocyte-macrophage function in IBD. We aimed to investigate the role of Ikaros family (Ikaros, Helios, Aiolos, Eos, Pegasus) in shaping monocyte function linked to advanced therapies response.

Aims & Methods

Peripheral blood samples were collected at baseline (W0) and after 8-12 weeks of induction therapy (W8/12) from IBD patients who initiated or switched advanced therapy [biologics, oral synthetics] and from healthy controls (HC) (n=8). We included patients achieving clinical remission after induction [Super-Responders] SR (n=18) and those showing no response [Non-Responders] NR (n=16). Immune phenotype and expression of Ikaros proteins were assessed via multiparametric flow cytometry (FACS) and correlated with clinical outcomes. To assess functional roles of Ikaros proteins, monocyte-derived macrophages were generated in vitro from buffy coat (n=6). Cells were polarised using cytokine cocktails to induce pro-inflammatory (LPS+IFNγ or TNF+PGE2+Pam3CSK4; TPP), alternative (IL1β+LPS), or regulatory (IL10) phenotypes. siRNA-loaded nanoparticles were used to silence Ikaros or Helios prior to polarisation. Phenotypic changes were analysed by FACS; cytokines secretion by ELISA; genes expression by qPCR; and phagocytosis by fluorescent beads uptake.

Results

At W0, IBD patients exhibited a significant increase in circulating monocyte counts (vs HC, p<0.001). At W8/12, monocyte levels significantly decreased in the SR group, while remaining elevated in the NR group. FACS analysis revealed an increased proportion of non-classical monocytes (CD14⁻CD16⁺) in the IBD group at W0 (vs HC; p< 0.05), persisting in NR at W8/12 (vs SR; p<0.05). IBD monocytes also showed higher expression of CCR2 and CX3CR1 compared to HC. Helios expression was absent in monocytes from IBD patients at W0, while the mean expression of Helios was 47.31% in monocytes from the HC group. At W8/12, Helios expression re-emerged in 34.14% of monocytes derived from the SR patients but remained undetectable in the NR. In vitro, macrophages treated with LPS+IFNγ or TPP upregulated Ikaros, STAT1, and CXCL10 gene expression (p< 0.01), while Helios, TGM2, and MCR1 were upregulated in response to IL10 (p< 0.05). Helios expression was absent in TNF-stimulated macrophages. Ikaros silencing reduced pro-inflammatory markers, IL6 and IL1β cytokines secretion, and inhibited phagocytosis in response to LPS, whereas Helios silencing increased macrophages activation, and pro-inflammatory markers in response to IL10.

Conclusion

Monocyte subsets distribution and Helios, Ikaros expression dynamics clearly distinguished SR from NR in IBD. Sustained absence of Helios and persistence of non-classical monocytes in NR suggest a failure to transition toward a regulatory phenotype. This may further contribute to altered migratory capacity and influence their functional fate within intestinal tissue. Functional assays confirm opposing roles of Ikaros and Helios in the macrophages activation, underscoring their unique potential as biomarkers or therapeutic targets to modulate inflammation in IBD.

Event

UEG Week Berlin 2025

Topics

IBD Mechanisms & Personalised Medicine

Submission format

Abstract

Session

Predicting response to IBD therapy

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

Panel Discussion

Personalising treatment: Tailoring to precision

Francesco Sclafani

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

Hao Chen

Anticipating the Nobel: Non-coding RNAs in diagnostics and therapy

Alexander Link

NOVEL TRANSCRIPTIONAL SIGNATURE OF CIRCULATING MONOCYTES DEFINES RESPONSE TO ADVANCED THERAPIES IN INFLAMMATORY BOWEL DISEASE

Subrata Ghosh

THE PROGNOSTIC VALUE OF CHOLINE PET/CT IN THE INITIAL ASSESSMENT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA

Patrick Flamen

UEG Poster

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THE PROGNOSTIC VALUE OF CHOLINE PET/CT IN THE INITIAL ASSESSMENT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA

Irina Vierasu 1, Hugo Levillain 1, Martina Pezzulo 1, Jennifer Dhont 1, Hugues Azema 1, Hugo Couvert 2, Clementine Martin 1, Nicola Trotta 1, Simon Lacroix 1, Ana-Maria Bucalau 3, Gontran Verset 3, Marianne Paesmans 1, Desislava Germanova 1, Valerio Lucidi 4, Eric TREPO 5, Thierry Gustot 6, Christophe Moreno 7, Jean-Luc Van Laethem 3, Patrick Flamen 1

Affiliations

1 Hôpital Universitaire de Bruxelles, Brussels, Belgium

2 Institut Jules Bordet, Brussels, Belgium

3 Erasme University Hospital, Brussels, Belgium

4 ERASME University Hospital, Université Libre de Bruxelles, Bruxelles, Belize

5 Hopital Universitaire de Bruxelles, Brussels, Belgium

6 ERASME University Hospital, Université Libre de Bruxelles, Bruxelles, Belgium

7 Hôpital Erasme (Gastro) - Maransart/BE, Brussels, Belgium

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Abstract

Introduction

This study aimed to evaluate the prognostic value of choline positron emission tomography/computed tomography (PET/CT) compared with MRI and fluorodeoxyglucose (FDG) PET/CT in treatment-naïve hepatocellular carcinoma (HCC) patients, emphasizing clinical relevance to overall survival (OS).

Aims & Methods

Seventy-eight patients with treatment-naïve HCC (median age: 67 years, 87% male, 87% cirrhotic) underwent baseline MRI, choline and FDG PET/CT imaging at Erasme Hospital between 2018 and 2022 (Protocol ID: P2023/279). Tumor volumes delineated on MRI were registered onto PET/CT scans and were assessed using median values as thresholds. Imaging parameters (tumor volumes, SUVmax, and SUVmean) were assessed for their prognostic significance. Linear correlation between MRI and choline volumes was evaluated and multivariate models were created using median tumor volume thresholds. Comparative Kaplan-Meier survival analysis and multivariate Cox regression, adjusting for treatment modality (transplantation, hepatectomy, locoregional therapies), were conducted and Holm Bonferroni correction was applied. Associations between imaging parameters and clinical biomarkers (AFP and ALBI score) were explored.

Results

High correlations (Choline r=0.94, FDG r=0.97) between SUVmax and SUVmean in both tracers imply redundancy, favoring volume-based parameters integrating metabolic and anatomical data. Higher tumor volumes measured by MRI (>17.81 mL; HR 3.15, p=0.005), choline PET/CT volumes (>8.4 mL; HR 2.27, p=0.04), and FDG PET/CT positivity (HR 2.74, p=0.02) significantly predicted poorer OS in univariate analysis. After multivariate adjustment and Holm-Bonferroni correction, only MRI-derived tumor volume remained an independent predictor (p=0.015). Notably, FDG uptake ≥1% of MRI-defined tumor volume correlated significantly with poorer OS (p=0.03). Liver transplantation and hepatectomy significantly improved survival compared to locoregional therapies (p=0.006). In the liver transplantation group, FDG and choline volumes do not significantly affect OS (p = 0.08, and 0.4 respectively). Imaging parameters did not correlate significantly with AFP or ALBI scores.

Conclusion

Choline PET/CT provided no additional prognostic value compared with MRI or FDG PET/CT in patients with treatment-naïve HCC.

Disclosure

i do not have any conflictof interest

Conference

UEG Week Berlin 2025

Topics

Hepatobiliary

Submission format

Abstract

Session

Developments in HCC management: From diagnosis to therapy (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

Panel Discussion

Personalising treatment: Tailoring to precision

Francesco Sclafani

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

Hao Chen

Anticipating the Nobel: Non-coding RNAs in diagnostics and therapy

Alexander Link

NOVEL TRANSCRIPTIONAL SIGNATURE OF CIRCULATING MONOCYTES DEFINES RESPONSE TO ADVANCED THERAPIES IN INFLAMMATORY BOWEL DISEASE

Subrata Ghosh

THE PROGNOSTIC VALUE OF CHOLINE PET/CT IN THE INITIAL ASSESSMENT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA

Patrick Flamen

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