Introduction

The aim of this study was to evaluate and to establish cut-off values for two new quantitative ultrasound (QUS) parameters, TSI (tissue scatter-distribution imaging) and TAI (tissue attenuation imaging) in early diagnosis of liver steatosis (LS), as compared to controlled attenuation parameter (CAP).

Aims & Methods

A prospective study was conducted in which LS was assessed in the same session by QUS (Samsung Medison RS85,CA1-7A probe) and CAP (FibroScan Compact M530, M/XL probes). Reliable measurements were defined for CAP the median value of 10 measurements with IQR/M<0.3, and for QUS, five consecutive measurements of TAI and TSI acquired by a color-coded map. TAI and TSI were automatically calculated and considered reliable when reliability index, R²>0.6. The CAP cut-off value used for the whole cohort for at least mild steatosis (S1) were 248 dB/m[1]; for ALD (alcoholic liver disease) cohort, 268 dB/mm[2]; for NAFLD(non-alcoholic liver disease) cohort 294dB/m[2]. Demographic and health related datas were recorded.

Results

A total of 285 patients, with a mean age of 56.1±12.4, 114 female and 171 male, were included in the study. According to aetiology, 164 (57.5%) patients had NAFLD, 61(21.4%) ALD, and 60 (21.1%) were other etiologies (viral, cardiac, autoimmune). The obtained TSI and TAI cut-off values for the diagnosis of at least mild steatosis (S1) are presented in Table 1.
Table 1. Cut-off values of TAI and TSI for S1

Variable		Overall	NAFLD	ALD
TSI	S1	>96.2 AUC=0.74,p<0.0001, Se=87.9%,Sp=53.0%;	>96.5 AUC=0.73, p<0.0001, Se=90.9%, Sp=47.9%;	>94.9 AUC=0.70, p=0.003 Se=72.9%,Sp=75.0%;
TAI	S1	>0.73 AUC=0.82,p<0.0001, Se=78.3%,Sp=71.6%;	>0.75 AUC=0.81, p<0.0001, Se=57.5%, Sp=90.8%;	>0.66 AUC=0.74, p<0.0001, Se=84.8%,Sp=57.1%;

There were no differences between the performance of TAI and TSI according to the DeLong test, p=0.18 and p=0.24. A strong direct correlation was observed between TAI and CAP r=0.701, moderate between TSI and CAP r=0.56 for the all cohort, but for NAFLD and ALD subgroups moderate correlations were found between TAI and CAP r=0.66, and r=0.66 respectively and TSI and CAP r=0.56 and 0.66, respectively.
In univariate regression analysis, the factors associated with TSI were hypertension, Diabettes mellitus(DM), and obesity, and all p-values were <0.0001, but in multivariate analysis, only hypertension(p=0.001) and obesity(p=0.0005) were associated. For TAI, in univariate analysis, the same factors: hypertension(p=0.004), obesity(p=0.0006) and DM (p=0.002) were associated, but in multivariate analysis, DM was the only factor associated, p=0.02. Age and gender were not correlated with any method, TSI or TAI.

Conclusion

TAI and TSI are feasible non-invasive methods for screening and diagnosis of liver steatosis, with good accuracy. Patients with NAFLD presented highest cut-off values, probably by the presence of DM and obesity, conditions independently associated with TAI and TSI values.

References

1.Karlas T, Petroff D, Sasso M, Fan JG, Mi YQ, de Lédinghen Vet al. Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. J Hepatol. 2017 May;66(5):1022-1030. doi: 10.1016/j.jhep.2016.12.022. Epub 2016 Dec 28. PMID: 28039099.
2. Petroff D, Blank V, Newsome PN, Shalimar, Voican CS, Thiele M, et al. Assessment of hepatic steatosis by controlled attenuation parameter using the M and XL probes: an individual patient data meta-analysis. Lancet Gastroenterol Hepatol. 2021 Mar;6(3):185-198. doi: 10.1016/S2468-1253(20)30357-5. Epub 2021 Jan 16. PMID: 33460567.

Introduction

Current therapeutic strategies for inflammatory bowel disease (IBD) remain limited, with clinical efficacy often falling short of expectations. Post-translational modifications play a pivotal role in IBD pathogenesis. This study aims to elucidate the functional significance of ubiquitination in IBD development and progression.

Aims & Methods

By analyzing colon RNA sequencing (RNA-seq) data from healthy and dextran sulfate sodium (DSS)-induced colitis mice, combined with RNA-seq datasets from healthy individuals and ulcerative colitis (UC) patients, we identified differential RNA expression levels of ATDC between healthy and inflammatory groups. Single-cell RNA sequencing (scRNA-seq) analysis further pinpointed the primary cell types exhibiting ATDC expression discrepancies. These findings were validated through immunohistochemistry, immunofluorescence, and western blot. Co-immunoprecipitation (Co-IP) assays and molecular docking simulations were employed to confirm and model the interaction between ATDC and PRMT5 in vitro. The role of ATDC in IBD pathogenesis was investigated using an ATDC-knockout (ATDC-KO) murine DSS model, with flow cytometry analyses delineating its impact on immune status.

Results

RNA-seq analysis revealed elevated ATDC mRNA levels in DSS-treated mice and UC patient intestinal tissues. scRNA-seq data indicated ATDC upregulation predominantly in the intestinal epithelial cells of UC patients. Protein-level upregulation of ATDC was further confirmed in both DSS mice and UC patient specimens. Lipopolysaccharide stimulation increased ATDC expression in Caco2 cells. Overexpression of ATDC in Caco2 cells, coupled with mass spectrometry, identified ATDC-PRMT5 binding, which was corroborated by Co-IP assays and molecular docking simulations. ATDC overexpression downregulated PRMT5 protein (but not mRNA) levels. In DSS models, PRMT5 expression was reduced compared to healthy controls; however, ATDC-KO mice exhibited PRMT5 upregulation and exacerbated colitis severity. Flow cytometry demonstrated an elevated Th17 cell proportion in ATDC-KO DSS mice relative to wild-type counterparts.

Conclusion

This study is the first to demonstrate the protective role of ATDC in colitis. ATDC attenuates colonic inflammation by promoting the degradation of PRMT5, thereby suppressing Th17 cell-mediated immune responses. Enhancing ATDC activity may represent a novel therapeutic strategy for mitigating colitis progression.

References

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Introduction

Portal hypertension is a major complication of advanced chronic liver disease (ACLD) and is associated with gastro-oesophageal varices, a leading cause of morbidity and mortality. The British Society of Gastroenterology (BSG) recommends oesophagogastroduodenoscopy (OGD) for variceal screening in all patients with cirrhosis, which could result in a high volume of unnecessary procedures. Given increasing demands on NHS services and the need for cost-effective resource allocation, strategies to reduce unnecessary endoscopy are critical.
The Baveno VI and VII consensus workshops propose non-invasive criteria to optimise variceal screening. Baveno VI suggests that patients with a liver stiffness measurement (LSM) less than 20 kPa and a platelet count greater than 150×10⁹/L can safely avoid OGD. Baveno VII further refines this by recommending non-selective beta-blocker (NSBB) therapy in patients with clinically significant portal hypertension (CSPH), defined as LSM greater than 25 kPa, thereby eliminating the need for screening endoscopy in this group. For patients not clearly stratified by Baveno VI or VII criteria, splenic stiffness measurement (SSM) offers an additional non-invasive tool to refine risk assessment. Incorporating SSM in this intermediate-risk group may further reduce the need for OGD, with recent data showing a high negative predictive value for ​ruling out high-risk varices.

Aims & Methods

We aim to quantify the reduction in endoscopy burden achieved by applying Baveno VI and VII criteria in ACLD patients.
A retrospective analysis was conducted on 1,703 patients who underwent 1,802 FibroScans between January 1, 2024, and December 31, 2024. Patients were stratified based on LSM and platelet counts into the following categories:
1. BSG Criteria: All patients with LSM ≥10 kPa requiring OGD.
2. Baveno VI Criteria: Patients with LSM <20 kPa and platelet count ≥150×10⁹/L, for whom OGD could be safely avoided.
3. Baveno VII Criteria: Patients with CSPH (LSM ≥25 kPa) recommended for NSBB therapy without the need for screening OGD.
4. Patients requiring OGD: Those not meeting Baveno VI criteria and without CSPH.

Results

Liver stiffness distribution:
• <10 kPa: 1,534 patients
• 10–14.9 kPa: 136 patients
• 15–19.9 kPa: 44 patients
• 20–24.9 kPa: 31 patients
• ≥25 kPa: 57 patients
Impact of Adopting Baveno VI and VII:
• BSG Guidelines: 274 patients (LSM ≥10 kPa) would require OGD.
• Baveno VI: 149 patients (LSM <20 kPa, platelets ≥150) could avoid OGD.
• Baveno VII: 57 patients (LSM ≥25 kPa) would be managed with NSBB, avoiding OGD.
• Total Reduction: 206 out of 274 patients (~75%) could avoid OGD.

Conclusion

Adopting Baveno VI and VII criteria would significantly reduce the need for variceal screening endoscopy in ACLD patients. By applying these thresholds, up to 75% of OGDs could be avoided, optimising NHS resources and reducing patient burden. These findings support the routine use of non-invasive risk stratification in ACLD management.

References

1. Tripathi D, Stanley AJ, Hayes PC, et al. UK guidelines on the management of variceal haemorrhage in cirrhotic patients. Gut. 2015;64(11):1680–1704. doi:10.1136/gutjnl-2015-309262
2. de Franchis R, Bosch J, Garcia-Tsao G, et al. Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015;63(3):743–752. doi:10.1016/j.jhep.2015.05.022
3. de Franchis R, Bosch J, Garcia-Tsao G, et al. Baveno VII – Renewing consensus in portal hypertension. J Hepatol. 2022;76(4):959–974. doi:10.1016/j.jhep.2021.12.022

Introduction

Endoscopic scores are crucial for assessing Crohn's disease (CD) severity, guiding therapy, and monitoring progression. The Simplified Endoscopic Score for Crohn's Disease (SES-CD) is widely used for this purpose [1]. Accurate scoring is vital for patient care. Recently, artificial intelligence has demonstrated potential in medical image interpretation [2]. This study aims to evaluate ChatGPT's effectiveness in rating the SES-CD.

Aims & Methods

This retrospective study evaluated ChatGPT's accuracy in assessing CD endoscopic activity using the SES-CD. One representative still image was selected for each bowel segment, and stricture degrees were provided separately if present. ChatGPT scored the SES-CD based on these images. The IBD expert's ratings were validated by calculating the intra-class correlation coefficient (ICC) with clinical trial central readers. The ICC between the IBD expert and ChatGPT scores was calculated to determine ChatGPT's reliability in SES-CD scoring.

Results

Nine (mean age 32.0 ± 11.8 years, 77.8% male) were included, with 45 bowel segments. Three (33.4%), 5 (55.6%), and 1 (11.1%) had nonstricturing nonpenetrating, structuring, and penetrating disease, respectively. Four (44.4%) had ileal disease and 5 (55.6%) had ileocolonic disease. Five (55.6%) had previous IBD surgery.
The SES-CD scores of the participants, rated by IBD expert in the hospital, revealed the following mean and standard deviation for each segment of the bowel: 6.9 ± 2.3 in the ileum, 1.3 ± 2.6 in the right colon, 1.6 ± 2.4 in the transverse colon, 1.3 ± 2.6 in the left colon, and 1.3 ± 2.6 in the rectum. The total SES-CD score was 12.4 ± 10.9. The score reliability of the institute IBD expert was tested compared to the clinical trial central reader and an intraclass correlation coefficient was calculated and found to be 0.96 (95% CI, 0.84-0.99) which is considered extremely correlated.
The mean and standard deviation of ChatGPT score in each segment were: 6.4 ± 2.4 in the ileum, 2.4 ± 3.8 in the right colon, 0.9 ± 2.7 in the transverse colon, 0.3 ± 1.0 in the left colon, 0.6 ± 1.3 in the rectum, with total SES-CD score of 10.6 ± 6.8. The calculated ICC between the expert and ChatGPT obtained SES-CD scores was 0.80 (95% IC, 0.64- 0.89) which is considered highly correlated.

Conclusion

Despite being based on only one photo per segment, ChatGPT demonstrated satisfactory performance in estimating endoscopic activity in CD. The differences between the IBD expert obtained scores and ChatGPT scores were acceptable, suggesting that artificial intelligence has the potential to be a useful tool in clinical and research settings, providing an accurate estimation of disease severity based on limited visual data.

References

1- Daperno M, D'Haens G, Van Assche G, et al. Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD. Gastrointest Endosc. 2004;60(4):505-512.
2- Levartovsky A, Albshesh A, Grinman A, et al. Enhancing diagnostics: ChatGPT-4 performance in ulcerative colitis endoscopic assessment. Endosc Int Open. 2025;13:a25420943. Published 2025 Mar 14.

Introduction

Cognitive Behavioral Therapy (CBT) is an evidence-based treatment for Irritable Bowel Syndrome (IBS), demonstrating long-term improvements in symptoms and quality of life (QOL). However, its implementation is hindered by the complexity of treatment protocols, high time and financial costs, and limited accessibility in Japan.

Aims & Methods

This study aimed to develop a smartphone-based CBT application and evaluate its effectiveness in alleviating IBS symptoms.
Adults aged 18 or older who met the Rome IV criteria for IBS and scored ≥110 on the Japanese version of the IBS Symptom Severity Index (IBSSI-J) were enrolled. Twenty-six participants were randomly assigned to either the intervention group (n = 14) or the waiting-list control group (n = 12). Outcome measures included the IBSSI-J, Japanese versions of the IBS-QOL (IBS-QOL-J), Pain Catastrophizing Scale (PCS-J), and Visceral Sensitivity Index (VSI-J). A two-way ANOVA was conducted with group (intervention vs. control) and time (pre, mid, post, follow-up 1) as independent variables.
The intervention group used the app for 5–10 minutes daily over two months. The app included three components: psychoeducation, cognitive restructuring, and exposure. Psychoeducation consisted of educational materials and follow-up quizzes. Cognitive restructuring used gamified multiple-choice content (135 items), replacing conventional thought records. Exposure involved users creating individual anxiety hierarchies and recording their thoughts before and after exercises. The app visualized anxiety changes and progress via graphs.

Table 1.
Intervention module of the application

Week	Module	Content
1	Psychoeducation	Introduction to the vicious cycle of IBS symptom exacerbation.
2	Psychoeducation Cognitive-Restructuring	Understanding the link between cognition and symptoms; exploring alternative perspectives.
3	Psychoeducation Cognitive-Restructuring	Explanation of exposure therapy; preparing for symptom-related situations; continued cognitive restructuring.
4	Cognitive-Restructuring Anxiety Hierarchy	Identifying anxiety-provoking situations and planning exposure tasks.
5-8	Exposure	Gradual exposure to selected situations based on the individual anxiety hierarchy.
9	Psychoeducation Summarization	Post-intervention strategies and relapse prevention.

Results

Eleven participants in the intervention group and eight in the control group completed the program. Significant group × time interactions were observed for all outcome measures. For the IBSSI-J, the interaction was significant (F(3, 51) = 4.41, p < .001), with the intervention group showing greater improvement at mid-point (F(1, 17) = 5.54, p = .03, η² = .25). For the IBS-QOL-J, a significant interaction was found (F(3, 51) = 8.00, p < .001), with improvement evident at follow-up 1 (F(1, 17) = 6.65, p = .02, η² = .28). For the PCS-J, the interaction was significant (F(3, 51) = 3.83, p = .02), with improvements at post (F(1, 17) = 9.26, p = .01, η² = .35) and follow-up 1 (F(1, 17) = 5.83, p = .03, η² = .26). For the VSI-J, the interaction also reached significance (F(3, 51) = 3.32, p = .05).

Conclusion

The CBT-based app was effective in reducing IBS symptom severity. Its effects persisted after the intervention and extended to improvements in QOL, visceral anxiety, and pain catastrophizing—psychological factors associated with the maintenance and exacerbation of IBS. It is assumed that the cognitive restructuring component of the app facilitated cognitive diversification among participants. By empirically challenging the plausibility of these diversified cognitions through behavioral experiments in the form of exposure tasks, participants were able to further develop more adaptive thoughts. This process is considered to have contributed to the improvement of symptoms and enhancement of QOL. This digital approach may offer a viable solution to current barriers in CBT access.

Introduction

Cholesterol is a key lipid involved in maintaining intestinal epithelial cell membrane structure and function. Recent studies suggest that microbiome-derived cholesterol metabolites, like ursodeoxycholic acid (UDCA) and 7-ketolithocholic acid (7-keto-LCA) promote intestinal epithelial repair and enhance Wnt signalling, thereby facilitating the self-renewal of intestinal stem cells (Li et al., Cell Host & Microbes 2024).

Aims & Methods

This study aimed to evaluate the effects of cholesterol-derived microbial metabolites—specifically lithocholic acid (LCA), deoxycholic acid (DCA), ursodeoxycholic acid (UDCA), and 7-keto-LCA—on intestinal epithelial barrier integrity, inflammatory responses, and homeostasis. Primary screening was conducted in Caco-2 monolayers co-treated with pro-inflammatory cytokines IFN-γ and TNF-α for 24 hours to mimic an inflammatory environment. Metabolites were tested at the following concentrations: LCA (10 µM, 50 µM, 75 µM), DCA (10 µM, 100 µM, 200 µM), UDCA (100 µM, 250 µM, 500 µM), and 7-keto-LCA (5 µM, 10 µM, 50 µM, 100 µM). Selected compounds showing significant effects were further validated in 3D intestinal epithelial organoid cultures. Gene expression analysis of key markers—TNF-α, CXCL9 (inflammation), OCLN, TJP1 (barrier integrity), and FGF19, NR0B2 (homeostasis)—was performed using quantitative RT-PCR. Statistical significance was determined using Student’s t-test with a threshold of p ≤ 0.05.

Results

Primary screening on Caco-2 cells revealed that 7-keto-LCA (10µM, 50µM) and LCA (75µM) downregulated the expression of genes encoding inflammatory cytokines (TNF-a and/or CXCL9; p < 0.05) and upregulated the expression of tight junction proteins (OCLN and TPJ1; p < 0.05) and FXR downstream marker (FGF19, p < 0.05). The tested concentrations of DCA and UDCA did not reduce the expression of inflammatory cytokine coding genes and reinstate the expression of tight junction proteins coding genes. For further analysis in 3D intestinal organoid model we selected 7-keto-LCA (10µM). 7-keto-LCA significantly upregulated the expression of NR0B2 (p < 0.05) and showed a tendency to reduce the expression of TNF-α in intestinal organoids (p = 0.12).

Conclusion

7-keto-LCA showed a trend to reduce inflammation and restore homeostasis in intestinal organoid model.
Study has been funded by the Research Council of Lithuania (LMTLT, agreement No. S-MIP-23-101).

References

Li T, Ding N, Guo H, Hua R, Lin Z, Tian H, Yu Y, Fan D, Yuan Z, Gonzalez FJ, Wu Y. A gut microbiota-bile acid axis promotes intestinal homeostasis upon aspirin-mediated damage. Cell Host Microbe. 2024 Feb 14;32(2):191-208.e9. doi: 10.1016/j.chom.2023.12.015.