Introduction

IBD-Control questionnaire and IBD-Disk are two easy-to-use IBD-specific patient-reported outcome measures aimed to measure the impact of IBD in the different health domains. Contrary to IBD-Disk, there is no fully published validated Portuguese version of IBD-Control. Additionally, the two instruments have not yet been compared.

Aims & Methods

The authors aimed to translate and validate the IBD-control in Portugal and to compare it with IBD-Disk. Acceptability was verified in a pilot patient group (n = 10) after the forward-backward translation of the IBD-control (Figure 1). Prospective validation involved completion of the IBD-Control, EQ-5D, short IBDQ, IBD-Disk and disease activity measurement by PRO2. Test-retest (2-week repeat) was used for measuring reliability. We compared user-friendliness (through 3 questions) and the ability to identify good disease control (through ROC analysis) of IBD-Control and IBD-Disk.

Results

Questionnaires were completed by 142 IBD patients (108 Crohn’s disease, 34 ulcerative colitis). The mean completion time was 168s. Internal consistency (Cronbach’s alpha) was 0.796 for the sub-group of 8 questions (IBD-control-8). Construct validity analyses demonstrated moderate-to-strong correlations of the IBD-control-8 and the other instruments (0.55-0.82) (Table 1). Test-retest reliability for stable patients (n=54) was high (intraclass correlation coefficient - 0.861). The IBD-control-8 showed good discriminant ability between well-controlled and insufficient/poor-controlled disease (15±2 vs 11±4; p<.001). No significant differences were noted between IBD-Control and IBD-Disk regarding user-friendliness and AUC (0,79 vs 0,76) for identification of good disease control.

Conclusion

The Portuguese IBD-control is a rapid, reliable, and valid instrument for measuring disease control from an IBD patient’s perspective, with no significant difference in terms of user-friendliness and measurement ability when compared to IBD-Disk.

Introduction

The Helicobacter pylori (H. pylori) infection is a common problem (prevalence of 32.7% in 2023) in the North-Western Federal District, comprising one-tenth of Russia, where primary resistance rates of clarithromycin and levofloxacin are >15%.¹ The eradication rates remain low and do not reach the threshold value of 95% (eradication rate of 86.8% in 2023). ² There is limited information regarding the best approach for H. pylori infection management.

Aims & Methods

The study was conducted in the North-Western Federal District during 2023-2025. Individuals (n=145) who underwent ¹³C-UBT (¹³С-urea breath test) was conducted in the prospective randomized clinical trial. Patients were randomly allocated to two eradication groups: high-dose dual therapy for 14 days (esomeprazole 40 mg and amoxicillin 1000 mg three times daily) and optimized high-dose dual therapy for 14 days (esomeprazole 40 mg, amoxicillin 1000 mg, rebamipide 100 mg three times daily). The modified intention-to-treat (mITT) effectiveness, safety, and adherence were analyzed for the regimens. The secondary endpoints were adverse effects and patient compliance. Eradication was confirmed by a ¹³C-UBT 4-6 weeks after therapy.

Results

Among all included individuals (mean age 46.27±14.21; 67.6% of whom were female), there were 91.7% (n=133) of primary “naïve” patients (who had had no history of prior eradication therapy). The proportion of treated patients was 8.3% (n=12). The high-dose dual therapy PPI-amoxicillin did not provided encouraging mITT results - 87.5%, 21/24, 95%CI 69.0-95.7; the inclusion of patients in this group was stopped due to unacceptable cure rates. Whereas the higher was reported with optimized eradication regimen with rebamipide (96.3%, 105/109, 95%CI 90.9-98.6 for treatment-naïve and 91.7%, 11/12, 95%CI 64.9-98.5 for treated patients). The adverse event rates were 37.5% in the PPI-amoxicillin group and 19.8% in the PPI-amoxicillin-rebamipide group (р=0.211). The most common were a diarrhea (25% and 12.4% respectively), bloating (25% and 3.5% respectively), abdominal pain (20.8% and 10.7% respectively). Good adherence, defined as > 90% of drug intake, were similar between the two groups (100% of cases).

Conclusion

In the North-Western region of Russia, the fourteen-day optimized high-dose dual therapy with PPI-amoxicillin-rebamipide provided encouraging results (over 90% cure rates) and had the lower incidence rate of side effects (19.8%) suggesting as an alternative for H. pylori rescue treatment in the local region.

References

1. Simanenkov VI, Zakharova NV, Zhebrun AB, et al. Resistance of Helicobacter pylori to antimicrobial preparations by the results of bacteriologic testing. Attending Physician. 2015;4:10 (In Russ.)].
2. Bakulina NV, Tikhonov SV, Savilova IV, Zharkov AV, Ponomarenko VA. Dynamics of the prevalence of Helicobacter pylori infection from 2015 to 2023. Herald of North-Western State Medical University named after I.I. Mechnikov. 2023;15(3):41–51. DOI: https://doi.org/10.17816/mechnikov623259

Introduction

Ulcerative colitis (UC) is a chronic, relapsing-remitting inflammatory bowel disease (IBD) with increasing global prevalence. The FDA has emphasized the importance of histologic endpoints in clinical trials, noting mucosal healing claims should be supported by more than just endoscopic findings. However, there are many challenges to achieving a standardized assessment of histologic disease activity in a UC clinical trial, including: the heterogeneity in the collection of mucosal biopsies (number, location) from study to study, a lack of fully validated histology scoring systems and an absence of community standards for definitions of histologic improvement or histologic remission.

Aims & Methods

This work was conducted by the FNIH Biomarkers Consortium Mucosal Healing in UC Project, a collaborative initiative involving academic institutions, pharmaceutical companies, patient advocacy organizations, and regulatory agencies to foster consensus, encourage adoption of findings, and support regulatory decision-making.
Aim 1: McBride et al. analyzed 994 biopsies from UC colectomy specimens to determine optimal biopsy sampling strategies for histologic grading.
Aim 2: A prospective study enrolled 153 UC patients to compare targeted versus non-targeted biopsy strategies across four colonic segments, assessing both endoscopic and histologic remission.
Aim 3: Data from three clinical trials (NCT02840721, NCT02958865, NCT02065622) and four independent datasets were compiled, yielding 9,652 whole slide images (WSIs) were used to train two AI tools:
• AIM-HI UC: Multiple instance learning models for predicting Geboes Score (GS) subgrades directly from H&E-stained WSIs.
• IBD Explore: A suite of convolutional neural networks (CNNs) for segmentation and classification of histologic features, including tissue types, crypt architecture, and cells. Performance was evaluated using a held-out test set (N=578 WSIs) and inter-pathologist agreement metrics.

Results

Aim 1: Sampling 2–3 biopsies per colonic region most effectively captured histologic heterogeneity and improved grading reliability. Agreement across histologic indices increased with biopsy number, particularly after the second and third biopsies.
Aim 2: Rectal histologic remission was highly predictive of proximal colonic remission (93% endoscopic, 88% histologic concordance). Histologic scores showed high correlation between targeted and non-targeted biopsies (ρ = 0.80–0.86), especially in remission.
Aim 3: Most AIM-HI UC models outperformed individual pathologists in predicting GS subgrades. IBD Explore generated interpretable histologic features—such as epithelial-to-lamina propria ratio, crypt distortion, and lymphocyte density—supporting advanced spatial analysis beyond conventional scoring systems.

Conclusion

This consortium-based endeavor generated several key findings: 1) Up to 3 biopsy samples per region of interest are required to overcome microscopic heterogeneity and ensure accurate histological grading in active colitis; 2) Targeted and random biopsies provide comparable histologic information, supporting the use of random biopsies in future clinical trials and practice; 3) Rectal endoscopic and histologic remission are highly predictive of pancolonic remission in extensive UC, supporting assessment limited to rectum in stable disease. Development of a ML-based approach for predicting GS subgrades, combined with these sampling insights, has the potential to improve standardization and automation of GS histological assessment, enhancing measurement of histological treatment response and endpoints in clinical trials.

References

IBD Explore and AIM-HI UC are for Research Use Only. Not for use in diagnostic procedures
McBride, R. B., Suarez-Farinas, M., Ko, H. M., Chen, X., Liu, Q., & Harpaz, N. (2023). Density of Biopsy Sampling Required to Ensure Accurate Histological Assessment of Inflammation in Active Ulcerative Colitis. Inflammatory bowel diseases, 29(11), 1706–1712. https://doi.org/10.1093/ibd/izad063
Danese S, Klopocka M, Scherl EJ, et al. Anti-TL1A Antibody PF-06480605 Safety and Efficacy for Ulcerative Colitis: A Phase 2a Single-Arm Study. Clin Gastroenterol Hepatol. 2021;19(11):2324-2332.e6. doi:10.1016/j.cgh.2021.06.011
Sandborn WJ, Danese S, Leszczyszyn J, et al. Oral Ritlecitinib and Brepocitinib for Moderate-to-Severe Ulcerative Colitis: Results From a Randomized, Phase 2b Study. Clin Gastroenterol Hepatol. 2023;21(10):2616-2628.e7. doi:10.1016/j.cgh.2022.12.029
Panés J, Colombel JF, D'Haens GR, et al. Higher vs Standard Adalimumab Induction and Maintenance Dosing Regimens for Treatment of Ulcerative Colitis: SERENE UC Trial Results. Gastroenterology. 2022;162(7):1891-1910. doi:10.1053/j.gastro.2022.02.033

Disclosure

Disclosures of Primary Authors
Autumn Jones: None
Russell McBride: None
Stephen Laroux: holds shares of stock in AbbVie
Christina Jayson: PathAI stock holder
Noam Harpaz: has served as an advisory board member or consultant for Lilly, Inc., Abbvie Inc., Bristol Meyer Squibb, Inc., and PathAI, Inc.

All listed organizations are financially contributing partners and/or consulting partners of the Foundation for the National Institutes of Health Biomarkers Consortium project team.
PathAI employees, previous and current are PathAI stock holders.

Introduction

Real-world data on the speed of onset of ustekinumab (UST) in patients with ulcerative colitis (UC) are limited. Current information regarding early response in these patients comes from the UNIFI trial.

Aims & Methods

The primary outcome of this study was to evaluate the response to UST in patients with moderate-to-severe UC by assessing PRO2 at 14 days after the first intravenous dose (6mg/kg).
Methods: A multicenter, prospective observational study was designed in patients ≥18 years old with moderate-to-severe UC (partial Mayo score ≥6) who initiated UST 6mg/kg between June 2023 and September 2024. Patients received a diary to record the stool frecuency and rectal bleeding during first 14 days after first dose of induction. The proportion of patients achieving the combined outcome of rectal bleeding score = 0 and stool frequency score ≤ 1 (PRO-2: patient-reported outcome 2 remission) was assessed. FC was measured at baseline and at day 7 and 14. Health-Related Quality of Life was evaluated using the disease-specific shortened Spanish version of the IBDQ (SIBDQ-9) at baseline and at 4 weeks. Patients with previous panproctocolectomy with ileostomy or pouch and those who had received cyclosporine within one month prior to starting UST were excluded. Descriptive statistics are presented as frequencies with percentages for categorical variables.

Results

A total of 54 patients were included across 14 hospitals in Spain. Of these, 29 (53.7%) were men, with a mean age of 54 (± SD 16.1) years. Thirty (55.6%) patients had pancolitis, 20 (37%) had left-sided colitis, and 4 (7.4%) had proctitis. Five (9.3%) patients were bio-naïve, 32 (59.3%) had previously received one biological therapy, 10 (18.5%) had received two, and 7 (13%) had received three biologics prior to starting UST. By day 14, 26% of patients had achieved clinical remission. No significant differences in clinical remission were observed based on disease extent (p = 0.11) or the number of prior biologics (p = 0.39). By day 7, 12/31 (38.7%) patients with baseline bloody stools had achieved a rectal bleeding score = 0. A reduction in FC >50% was observed in 14/48 (29%) patients by day 7 and in 20/47 (43%) patients by day 14. The SIBDQ9 average score was 54.9 (± SD 6.2) at baseline and 61.3 (± SD 7.4) at week 4.

Conclusion

One-quarter of patients with moderate-to-severe UC achieved clinical remission by day 14 following the first induction dose of UST. Nearly 40% of patients achieved a rectal bleeding score = 0 (PRO2) by day 7. A reduction in FC >50% was observed in 43% of patients by day 14.

Disclosure

Manuel Barreiro de Acosta: speaker, consultant and advisory member for or have received research funding from AbbVie, Janssen, Takeda, Pfizer, Lilly, Alphasigma, Sandoz and Oncostellae

Introduction

Early identification of severe acute pancreatitis (SAP) enables the prompt initiation of aggressive resuscitation strategies and improves patient outcomes. The aim of the present study is to assess the clinical differences between patients with SAP and those with mild or moderate acute pancreatitis, as well as the distribution of organ failure in severe cases.

Aims & Methods

A retrospective analysis was conducted on a prospective database comprising a cohort of 526 patients with acute pancreatitis, consecutively included from March 2017 to June 2019 at a tertiary care hospital. All included patients underwent systematic blood testing at admission and at 48 hours. Clinical management adhered to current clinical practice guidelines. Diagnosis and classification were based on the revised 2012 Atlanta classification. The analysis included the need for antibiotic therapy, development of local complications, organ failure patterns, and infectious complications

Results

	Mild/Moderately severe AP (n = 399 / 90.7%)	Severe AP (n = 41 / 9.3%)	p-value
Necrotizing pancreatitis	8 (2.1%)	13 (34.2%)	0.001 **
Infected necrosis	4 (1%)	6 (16.2%)	0.001 **
Antibiotic therapy	129 (32.9%)	29 (74.4%)	0.001 **
Extrapancreatic infection	35 (12.5%)	10 (28.6%)	0.011 **
Mortality	2 (0.5%)	18 (43.9%)	0.001 **
Cholangitis	145 (36.3%)	18 (43.9%)	0.340
ICU admission	3 (0.3%)	12 (29.3%)	0.001 **
SIRS at admission	56 (14.1%)	26 (63.4%)	0.001 **
SIRS at 48 hours	17 (4.3%)	22 (55%)	0.001 **

Table 1 summarizes the clinical characteristics and outcomes associated with severe acute pancreatitis (SAP). Regarding infectious complications, patients with SAP showed higher rates of infected necrosis and extrapancreatic infections, although no significant differences were observed in the incidence of acute cholangitis. Patients with SAP were more likely to develop necrotizing pancreatitis and local complications. Moreover, they accounted for the vast majority of ICU admissions and deaths. In terms of persistent organ failure, renal failure was the most frequent (80%), followed by respiratory failure (45%). A high proportion of patients who developed SAP presented with SIRS at admission (64%) and at 48 hours (55%).

Conclusion

Early identification of severe acute pancreatitis (SAP) is not always straightforward and requires close monitoring. Nevertheless, recognizing these patients is critical, as prognosis is intrinsically linked to the timeliness of diagnosis and the implementation of supportive measures necessary to maintain organ stability.
Patients with SAP are at higher risk of developing organ failure. In our cohort, we observed increased use of antibiotic therapy among SAP patients, likely due to the higher incidence of infected necrosis and extrapancreatic infections. Conversely, the incidence of acute cholangitis, based on the 2018 Tokyo criteria, was similar between SAP and mild/moderate AP cases.
Regarding organ failure, renal failure was the most frequent in our cohort, although other series have reported respiratory failure as the most common. The presence of SIRS at admission and at 48 hours was associated with subsequent development of SAP; however, a significant number of patients with SIRS did not ultimately develop a severe course. Its predictive value may be enhanced when combined with other prognostic factors.

References

1. Banks, P. A., Bollen, T. L., Dervenis, C., Gooszen, H. G., Johnson, C. D., Sarr, M. G., Tsiotos, G. G., & Vege, S. S. (2013). Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut, 62(1), 102–111.
2. Garg, P. K., & Singh, V. P. (2019). Organ Failure Due to Systemic Injury in Acute Pancreatitis. Gastroenterology, 156(7), 2008–2023.
3. Pezzilli, R., Zerbi, A., Campra, D., Capurso, G., Golfieri, R., Arcidiacono, P. G., Billi, P., Butturini, G., Calculli, L., Cannizzaro, R., Carrara, S., Crippa, S., De Gaudio, R., De Rai, P., Frulloni, L., Mazza, E., Mutignani, M., Pagano, N., Rabitti, P., & Balzano, G. (2015). Consensus guidelines on severe acute pancreatitis. Digestive and Liver Disease, 47(7), 532–543

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD) has a global prevalence of 30%, with 10-30% progressing to advanced liver fibrosis in 5 years. It is essential to assess advanced liver fibrosis – a predictor of liver-related outcomes. FIB-4 is a good screening test, but its low specificity leads to unnecessary referrals to hospital, especially in individuals over 65 years and with type 2 diabetes (T2D). To address these limitations, machine-learning techniques are developing scores like FIB-6 (validated for Hepatitis B and C).

Aims & Methods

We aimed to assess the performance of FIB-6 score in screening for advanced fibrosis in a Portuguese cohort of MASLD patients.
A retrospective-cohort study was conducted with MASLD patients who had undergone liver vibration-controlled transient elastography (VCTE) between January-October 2024. inclusion criteria: adult patients (age >18years) diagnosed with MASLD; undergone liver VCTE; complete biochemical and hematological data. Exclusion criteria: coexistence of other liver diseases; decompensated cirrhosis; hepatocellular carcinoma; hematological/bone‑related diseases. We used liver stiffness measurement by VCTE as a reference standard for liver fibrosis. Fibrosis was staged on a 0–4 scale: F0, F1 and F2, patients without advanced fibrosis; F3 and F4, patients with advanced fibrosis/cirrhosis.
Non invasive tests (FIB-6, FIB‑4, APRI, NFS) were calculated using blood results available within the month of the VCTE. Statistical analysis was performed using R version 4.2.3. AUC-ROC curve analysis with cutoff points were calculated using the Youden index.

Results

115 MASLD patients (58 males (50.43%),57 females (49.57%), median age of 62years) where included. 41 (35.65%) had diabetes mellitus type 2 (T2D) (10 of those insulin-treated), 74 (64.35%) arterial hypertension, 76 (66.09%) dyslipidemia and with a median body mass index of 29.9mg/Kg/m². Regarding hepatic fibrosis, 79 patients had F0-2 and 17 patients had F3-4.
In the general sample, AUC-ROC curve analysis showed an AUC 0.771 (CI 95% :0.662, 0.88) for FIB-4, AUC 0.788 (CI 95% :0.686, 0.889) for APRI, AUC 0.709 (CI 95% :0.595, 0.823) for NFS and AUC 0.695 (CI 95% :0.571, 0.819) for FIB-6.
A subanalysis of the sample over 65 years old revealed AUC 0.807 (CI 95% : 0.665, 0.949) for FIB4; AUC 0.788 (CI 95% : 0.686, 0.889) for APRI; AUC 0.788 (CI 95% : 0.65, 0.926) for NFS; AUC 0.663 (CI 95% : 0.475, 0.852) for FIB-6. A subanalysis of the sample of T2D patients revealed AUC 0.747 (CI 95% :0.584, 0.911) for FIB4; AUC 0.811 (CI 95% :0.676, 0.946) for APRI; and AUC 0.765 (CI 95% : 0.612, 0.918) for FIB6.
Using the optimal cut‑offs of FIB6 (cutoff= 1.8992) for the diagnosis of F3+F4 indicated a reliable performance of FIB‑6 score (sensitivity was 70%, specificity was 52.6%).
The cutoff values of FIB-6 for the general sample was 2.4420 (sensitivity 53%, specificity 87%); for the subset of patients over 65 years was 2.7668 (sensitivity 40%, specificity 96%); for the subset of T2D patients was 2.2230 (sensitivity 55%, specificity 90%).

Conclusion

FIB-6 demonstrated good performance in screening advanced fibrosis in MASLD patients, when compared to those of FIB‑4, APRI, and NFS, surpassing FIB-4, particularly in individuals with T2D. This study is the first to evaluate the applicability of FIB-6 in a Portuguese MASLD cohort. Although the findings warrant validation in larger and more diverse populations, they suggest that FIB-6 may be more efficient to evaluate liver fibrosis in MASLD and offer a more efficient tool to identify patients that need specialized care.

References

Anushiravani A, et al. 2023.
Alswat K, et al. 2024.
Shiha G, et al. 2022
Tacke, Frank et al. 2023
Boursier, Jerome et al. 2022
Papatheodoridi, Margarita et al. 2021
Hannes Hagström et al. 2024.
Rinella, Mary E. et al.2023

Introduction

The current universal standard of care in primary biliary cholangitis (PBC) is ursodeoxycholic acid (UDCA), although its clinical benefit in PBC has never been reported in absolute measures.

Aims & Methods

This cohort aimed to assess the prevalence of incomplete response to UDCA and determine non-response predictors.
Patients with PBC as main diagnosis were included from the hospital's centralized electronic medical records system, over a 10-year period. Overlap syndromes (PBC-Auto-Immune Hepatitis) were also included. Main endpoints included incomplete response to UDCA treatment according to Paris I, Paris II criteria, and Globe score.

Results

A total of 50 patients were included in this study. The mean age at diagnosis was 52.74 years (24-73 years) and 92% females. Only one patient was asymptomatic at onset and 82% had positive anti‐mitochondrial antibodies. All patients were treated with ursodeoxycholic acid (UDCA). Corticosteroids and immunosuppressive therapies were associated in 26% of cases. Incomplete response to UDCA was observed in 28% and 34% of patients according to Paris I and II criteria, respectively. Non-response predictors were poor therapeutic adherence, Overlap syndrome and hepatocellular carcinoma in 14%, 6% and 4% respectively. Five patients were lost to follow-up and five cases died from cirrhosis ’complications. The median ΔGLOBE score was 0.42 (IQR: -1.58 to 3.92). The 5, 10 and 15 years liver transplantation-free survival (median) was: +10%, +7.38% and +5% respectively. Liver transplantation (LT) was considered in one patient with excellent outcomes at last follow-up.

Conclusion

A considerable proportion of patients showed incomplete response to UDCA treatment according to Paris II criteria. Early identification of patients at risk of incomplete response could improve patient management and overall disease prognosis.

References

- Treatment response to ursodeoxycholic acid in primary biliary cholangitis: A systematic review and meta-analysis. DOI: 10.1016/j.dld.2022.12.010
- Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score. doi: 10.1016/S2468-1253(18)30163-8. Epub 2018 Jul 13.