Introduction

Sarcoidosis is a multisystem disorder marked by non-caseating granulomas, primarily affecting the lungs but capable of involving almost any organ system. Hepatic involvement is reported in 10-65%, ranging from asymptomatic presentations to severe complications such as chronic cholestasis, portal hypertension, or cirrhosis. Its broad spectrum of clinical presentations makes diagnosis challenging; therefore our hypothesis was that hepatic sarcoidosis is underdiagnosed.

Aims & Methods

This study aims to evaluate the prevalence and clinical characteristics of hepatic sarcoidosis by analyzing two distinct cohorts – a hepatology cohort and a pneumology cohort.
The hepatology cohort included 37 patients from a university hepatology center with clinically and/or histologically confirmed hepatic involvement in sarcoidosis. Clinical characteristics were recorded at initial diagnosis, and at 3- and 12-month follow-up.
In parallel, a pneumology cohort of 346 patients with biopsy-proven sarcoidosis from a pneumology center was examined for abnormal liver values or imaging findings. Regarding this cohort, statistical comparisons between sarcoidosis patients with and without hepatic abnormalities were conducted.

Results

In the hepatology cohort, 43.2% of patients (n = 16) were male and 56.8% (n = 21) female. At initial presentation, the mean BMI was 27.7 ± 7.3 kg/m² (median 25.8; range 19.0–50.5). The number of organ manifestations per patient ranged from 1 to 6, with a median of 3 and a mean of 2.97 ± 1.5; notably, 18.9% of patients (n = 7) presented with isolated hepatic involvement. Liver involvement was biopsy-confirmed in 62.9% of patients (n = 22), whereas only 40% (n = 15) showed corresponding morphological findings on imaging. Laboratory results predominantly showed a cholestatic pattern with elevated ALP and gamma-GT. Mean levels of elevated liver enzymes decreased over the follow-up period. The most common symptoms were fever (27.0%) and weight loss (24.3%), while 16.2% of patients (n = 6) were asymptomatic. 51.3% of patients (n = 19) were treated with glucocorticoids, 43.2% (n = 16) received no therapy.
In the pneumology cohort, 172 (49.7%) sarcoidosis patients showed abnormal liver values or imaging. In the cohort, 139 (40.2%) patients were female, and 207 patients (59.8%) were male. Hepatic abnormalities were observed significantly more frequent in males than females (54% vs. 43%, p = 0.046). Patients with hepatic involvement had a mean age of 52.9 ± 12.0 years (range 20–83) at the time of inpatient stay (n = 172). BMI was significantly higher in patients with hepatic involvement (median 29.8 vs. 27.1 kg/m², p < 0.001), while no significant age difference was observed. Splenic abnormalities were more common in those with hepatic involvement (23.4% vs. 7.7%, p < 0.001).

Conclusion

Analysis of the hepatology cohort highlights that biopsy-confirmed hepatic sarcoidosis can occur even in the absence of corresponding imaging findings. The clinical course of hepatic sarcoidosis is often self-limiting. In selected cases, treatment with glucocorticoids, other immunosuppressants, or ursodeoxycholic acid (UDCA) in patients with cholestatic symptoms is required.
The high number of liver abnormalities in the pneumology cohort suggests that hepatic sarcoidosis is underdiagnosed. Sarcoidosis patients should be assessed for potential hepatic involvement. Screening via ALP levels is recommended. The need to screen for hepatic involvement applies regardless of patient age.

Disclosure

There are no conflict of interest.

Introduction

EoE is a debilitating disease with physical, behavioral, and psychosocial impacts, resulting in substantial impairment in quality of life for patients and caregivers. Children with EoE can present with nonspecific symptoms such as food refusal or feeding difficulties, gastroesophageal reflux disease (GERD), nausea, and vomiting. Dupilumab is approved in the USA and EU for patients with EoE aged ≥1 year, weighing ≥15 kg. In the phase 3 randomized placebo-controlled EoE KIDS study (NCT04394351), in children aged 1 to 11 years, dupilumab significantly improved symptoms of EoE vs placebo, as measured by the Pediatric Eosinophilic Esophagitis Symptom Score version 2.0 (caregiver version; PEESSv2.0) after 16 weeks of treatment.

Aims & Methods

In this post-hoc analysis of the EoE KIDS study, we evaluated the effects of long-term dupilumab treatment on PEESSv2.0 scores during the Part C open-label extension. PEESSv2.0 is a validated observer-reported outcome measure that assesses the frequency and severity of EoE symptoms and adaptive behaviors, divided into four domains: GERD, dysphagia, pain, and nausea; each is scored 0–100, with higher scores indicating a greater symptom domain severity. Patients who completed Week 52 in Part B of EoE KIDS were eligible for Part C, where all patients received open-label dupilumab, using the weight-tiered regimen later approved by the FDA (similar to the Part A and B higher-exposure regimen). In patients who received placebo or dupilumab higher exposure during Parts A and B, changes from baseline of the EoE KIDS study (Part A baseline) in the PEESSv2.0 total, frequency, severity, and domain scores were assessed at Week 52 (Part C baseline), Week 76, and Week 100.

Results

At Week 52, the mean change from baseline (95% confidence interval) in PEESSv2.0 total score was –23.8 (–32.1, –15.6; Table), with further reductions observed at Week 100 (–31.5 [–41.5, –21.4]). Mean changes from baseline in PEESSv2.0 frequency and severity scores were further reduced from Week 52 (–25.1 [–34.2, –16.1] and –22.2 [–30.3, –14.1], respectively), to Week 100 (–33.8 [–44.9, –22.7] and –28.6 [–38.3, –19.0]). Similar patterns of reduction were observed for individual primary domain scores, namely, GERD, dysphagia, pain, and nausea. During the Part C open-label extension, dupilumab safety was consistent with the known dupilumab safety profile.

Conclusion

Children with EoE, treated with long-term dupilumab, experienced sustained improvements in the frequency and severity of symptoms of EoE up to Week 100, assessed by the PEESSv2.0. Reductions in GERD, dysphagia, pain, and nausea domain scores were also maintained or in some cases further improved, although interpretation of Part C symptom data is limited due to the open-label study design. Future studies should consider the correlation of symptoms with trends in both endoscopic and histologic outcomes.

Disclosure

Oliva S: Celgene/Receptos/Bristol Myers Squibb, Medtronic, Ocean Pharma, Sanofi/Regeneron Pharmaceuticals Inc – advisory board/consulting fees. Medtronic, Sanofi/Regeneron Pharmaceuticals Inc. – speaker fees.
Gold B: Diasorin Molecular, IQVIA/AstraZeneca, Ironwood Pharmaceuticals, Johnson&Johnson, Mead Johnson/Reckitt, Nutricia, Pfizer Inc, Sanofi/Regeneron Pharmaceuticals – advisory board/consultancy fees.
Ashok D: Alexion Pharma, LaunchitDTx, Mirum Pharma – advisory board/consulting fees. Sanofi – speaker fees.
Parrish C: Sanofi/Regeneron, Takeda – advisory board/consulting. Regeneron Pharmaceuticals Inc., Sanofi – speaker fees. DBV technologies, NIH/NIAID – research support.
Xia C, Raphael BP, Radwan A, Thomas RB: Regeneron Pharmaceuticals Inc. – employees and may hold stock or shares.
Cazeau C, Almansa C, Tilton ST: Sanofi – employees and may hold stock or shares.

Introduction

The Pisa EoE Adaptation Questionnaire (PiEAQ) on adaptive behaviors at mealtime significantly improves the correlation between dysphagia scores and histological disease activity (HDA) in eosinophilic esophagitis (EoE) [Reference 1].

Aims & Methods

Whether longitudinal variations of PiEAQ scores (∆PiEAQ) can capture HDA trends following pharmacological treatment of EoE has not been investigated. Consecutive adults (>18 years) with histologically active EoE (i.e., ≥15 eos/high-power field) were prospectively enrolled. Clinical characteristics, HDA, a recall-modified dysphagia symptom questionnaire (mDSQ), esophageal hypervigilance and anxiety scale (EHAS), and PiEAQ (drinking water to push the bolus, lubricating food, chewing for long, and blending food) were recorded longitudinally at baseline (T0) and 12 weeks post-treatment using a 30-day recall period (T1). ROC curve analysis with DeLong test was used to calculate the diagnostic accuracy (AUC) of clinical scores for predicting HDA following treatment. Significance threshold was p<0.05.

Results

Thirty-seven histologically active EoE patients were included (Table 1). The mDSQ, PiEAQ, and EHAS score at baseline were 2.97 (IQR, 2-5), 2.00 (IQR, 1-3), and 21 (IQR, 14– 25), respectively. Following treatment with budesonide orodispersible tablets (72.2%), PPIs (19.6%), dupilumab (5.5%), or milk-free diet (2.7%), histological remission was achieved in 78.4% of patients, while 21.6% remained histologically active. Post-treatment (T1), mDSQ, PiEAQ, and EHAS scores decreased significantly only in patients who achieved histological remission (Table 2 and Figure1). ROC curve analysis showed that a post-treatment reduction of at least 2 adaptive behaviors compared to baseline (∆PiEAQ=-2) had AUC of 85.0%, with 100% specificity and 64% sensitivity for the identification of patients achieving histological remission following treatment. Similarly, a post-treatment reduction of at least 3 points in mDSQ scores compared to baseline (∆mDSQ=-3) had AUC of 81.1% with 100% specificity and 57.7% sensitivity. The non-inferiority analysis showed that the ∆PiEAQ had similar performance to ∆DSQ (DeLong p-value= 0.46). A combined score integrating both ∆PiEAQ and ∆DSQ scores increased the AUC of clinical scores for capturing variations of HDA post-treatment to 90%, with 100% specificity and 73.1% sensitivity for detecting patients achieving histological remission post-treatment (Figure 2).

Conclusion

The PiEAQ is the first questionnaire investigating adaptive behaviors as a standalone domain in EoE. We demonstrated that longitudinal variations in PiEAQ scores are sensitive to HDA variations over time and can monitor histological disease activity trends after treatment. This study confirms that, similar to dysphagia, adaptive behaviors contribute to disease burden in EoE and improve with treatment.

References

1. Visaggi P, Del Corso G, Solinas I, Ovidi F, Adamo G, Dulmin I, Baiano Svizzero F, Bellini M, Savarino EV, de Bortoli N. Adaptive Behaviors, Esophageal Anxiety, and Hypervigilance Modify the Association Between Dysphagia Perception and Histological Disease Activity in Eosinophilic Esophagitis. Am J Gastroenterol. 2024 Dec 30. doi: 10.14309/ajg.0000000000003272. Epub ahead of print. PMID: 39787341.

Disclosure

Speaker or Consultancy for Apogee Therapeutics, Dr Falk Pharma, Malesci, JB Pharmaceuticals, Sanofi, Alfasigma

Introduction

Intestinal barrier integrity is emerging as a key therapeutic target in inflammatory bowel disease (IBD). Advanced endoscopic imaging techniques, including ultra-high magnification endocytoscopy (ECS) and probe-based confocal laser endomicroscopy (pCLE), enable real-time, in vivo structural and functional intestinal barrier assessment. Raman Spectroscopy (RS) can add a molecular dimension through vibrational fingerprinting of barrier-associated metabolites in biological samples.¹

Aims & Methods

This study explores the potential of RS integration with advanced endoscopy to characterise the intestinal barriers in IBD, targeting on tryptophan-derived metabolites and carbohydrates. A total of 46 IBD patients [25 Crohn’s disease (CD) and 21 ulcerative colitis (UC)] and 7 healthy controls (HC) undergoing endoscopic assessment or surveillance were prospectively enrolled from two academic centres. ECS or pCLE were used to evaluate epithelial and vascular barrier integrity. Barrier healing was defined as ECS score ≤ 1 or pCLE score ≤ 4, with preserved villi/crypt architecture, normal vasculature, and also absence of fluorescein leakage for pCLE. Advanced endoscopy-guided biopsies were collected from representative bowel segments. Mucosal healing (MH) was assessed by experienced pathologists using Nancy’s Histological Index ≤1. Epithelial (Claudin-2 and ZO-1) and vascular (PV-1 and CD-31) barrier markers were analysed through confocal microscopy, and their expression was automatically quantified using QuPath. Micro-RS was applied to tissue samples and matched sera to measure key tryptophan metabolites (kynurenine, indolepropionic acid, and melatonin) and carbohydrates.^2,3 Six-month major adverse outcomes (MAOs) were recorded. Group differences in Raman spectra were analysed with the Mann-Whitney test; correlations were assessed via Pearson’s test.

Results

Among patients undergoing ECS, barrier healing was observed in 10/22 (45%) colonic and 6/9 (67%) ileal cases. pCLE-based assessment revealed healing features in 5/16 (31%) colonic and 2/15 (13%) ileal evaluations. Raman spectral analysis showed a significant (p<0.05) reduction in tryptophan metabolites and carbohydrate-associated peaks in IBD tissues and sera compared to HC, especially in inflamed patients. When stratified by advanced endoscopy-identified barrier integrity, tryptophan metabolites -known barrier modulators-, and carbohydrates -likely reflecting mucin barrier layer- were markedly reduced (p<0.05) in patients with impaired barrier function. Notably, tryptophan derivatives positively correlated with Claudin-2 and ZO-1 in UC (r>0.4), and with PV-1 in CD (r>0.5). Similarly, carbohydrates correlated positively with Claudin-2 in UC (r=0.4) and negatively with CD-31 in CD (r=-0.4). Lower levels of indolepropionic acid and carbohydrates correlated with worse short-term MAOs (r<-0.4).

Conclusion

The integration of RS with advanced endoscopic images offers a novel, multi-layered approach to assess intestinal barrier integrity in IBD. RS can identify novel non-invasive biomarkers of mucosal and barrier healing, with potential real time applications for monitoring disease activity and predicting therapeutic outcome. Tryptophan metabolites may serve as a predictive biomarker of barrier healing paving the way toward personalised, barrier-targeted therapies.

References

1 Smith SCL, Banbury C, Zardo D, et al. PLoS One 2021; 16: e0252210.
2 Michaudel C, Danne C, Agus A, et al. Gut 2023; 72: 1296–307.
3 Arras W, Breugelmans T, Oosterlinck B, et al. J Crohns Colitis 2025; 19.

Introduction

Dutch society has witnessed significant societal and demographic changes over the decades. With 28% of the Dutch population having a migration background in 2023, understanding diversity within the gastroenterology workforce is imperative. This study examines the evolution of sex, ethnic, and socio-economic diversity among Dutch gastroenterologists from 2005-2023.

Aims & Methods

This repeated cross-sectional study utilized pseudonymized data from the BIG-register, paired with demographic variables from Statistics Netherlands (CBS), covering the years 2005, 2010, 2015, 2020, and 2023. The total population sample in each year consisted of all individuals registered as gastroenterologists for at least one day in a respective year. Variables such as sex, migration background, year of birth, and parental socio-economic status indicators were analyzed to assess trends and identify factors associated with being a
gastroenterologist. Descriptive and logistic regression analyses were employed to explore these trends and compare generational differences.

Results

The study revealed a narrowing sex gap with an increase in female gastroenterologists (28% to 43% from 2005-2023), particularly among the younger cohort (60% female). However, ethnic diversity has not kept pace, with a decline in the representation of gastroenterologists from migration backgrounds among younger professionals (27% to 18% for gastroenterologists < 1979 and ≥ 1980, respectively). Socio-economic analysis indicated that approximately 75% of gastroenterologists have parents from top-20% assets category.

Conclusion

The gastroenterology field in the Netherlands shows significant advancements in gender diversity, but lags in ethnic and socio-economic diversity. The increasing trend of gastroenterologists from medical families highlights the need for policy adjustments, to ensure access to candidates from more diverse socio-economic backgrounds. Policies should focus much more on promoting comprehensive diversity to enhance healthcare outcomes and reflect the demographic changes within society.

References

1. Stanford FC. The Importance of Diversity and Inclusion in the Healthcare Workforce.
J Natl Med Assoc. 2020;112(3):247-9.
2. Gomez LE, Bernet P. Diversity improves performance and outcomes. J Natl Med
Assoc. 2019;111(4):383-92.
3. Juch A. 100 jaar Maag-Darm-Leverarts in Nederland 1913-20132013. 336 p.
4. Brach C, Fraser I. Reducing disparities through culturally competent health care: an
analysis of the business case. Qual Manag Health Care. 2002;10(4):15-28.
5. Moberly T. Men outnumber women three to one in some specialties. Bmj.
2018;363:k4098.
6. Subramaniam M, Azad N, Wasan SK, Long MT. Equal Opportunity: Women
Representation on Editorial Boards and Authorship of Editorials in Gastroenterology and
Hepatology Journals. Am J Gastroenterol. 2021;116(3):613-6.
7. Dossa F, Baxter NN. The place of women in gastrointestinal medicine and surgery:
the need for progress. Lancet Gastroenterol Hepatol. 2023;8(11):965-6.
8. Kesavarapu K, Schwartz J, Ikonomi E, Ahmad A. What's holding women back? A
review of gender inequality in gastroenterology in the USA. Lancet Gastroenterol Hepatol.
2019;4(12):898-900.
9. Esposito I, Simsek C, Nowak A, Tiniakos D, Equality UEG, Diversity G. United
European Gastroenterology Equality and Diversity Plan. United European Gastroenterol J.
2023;11(5):484-7.

Disclosure

OKB, ABB, PK and LM have no conflict of interests, CJJM is consultant for Douglas (New Zealand) and HLW (The Netherlands). All outside submitted work.

Introduction

Mirikizumab is an anti-IL-23p19 monoclonal antibody, a key mediator in the pathogenesis of inflammatory bowel diseases. We evaluated the induction efficacy and safety of mirikizumab in the LUCENT-1 (NCT03518086) Chinese subpopulation.

Aims & Methods

In this Phase 3, multi-center, randomized, parallel-arm, double-blind, placebo-controlled trial, conventional-failed or biologic/tofacitinib-failed Chinese adult patients (N=184) with moderately to severely active ulcerative colitis (UC, Modified Mayo Score 4-9, endoscopic subscore ≧2) were randomized in a 3:1 ratio to 300 mg mirikizumab (intravenous) or placebo every 4 weeks for 12 weeks. Randomization was stratified by biologic/tofacitinib failure status, baseline corticosteroid use and baseline disease activity (Modified Mayo Score). The primary objective was to test the hypothesis that mirikizumab was superior to placebo in inducing clinical remission at Week 12 (W12). Key secondary endpoints included alternate clinical remission, clinical response, clinical response in biologic-failed patients, symptomatic remission, endoscopic remission, histologic-endoscopic mucosal and bowel-movement urgency improvement. Analyses in Chinese subpopulation were descriptive. Missing data was imputed as non-responders for the categorical endpoints. Bowel urgency change from baseline data was reported based on Mixed Model Repeated Measured.

Results

Baseline characteristics were balanced across groups. A greater proportion of mirikizumab-treated patients achieved clinical remission (18.6% vs. 7.0%; Δ=11.5 [95%CI: 1.7, 21.3]) and alternate clinical remission at W12 (21.4% vs. 7.0%; Δ=14.3 [95%CI: 4.4, 24.2]). Mirikizumab also improved key secondary endpoints at W12. The frequencies of treatment-emergent adverse events were similar between groups (mirikizumab [60.0%] vs. placebo [62.8%]). There were fewer serious adverse events (10 [7.1%] vs. 7 [16.3%]) and discontinuations due to adverse events (2 [1.4%] vs. 3 [7.0%]) in mirikizumab-treated patients compared to placebo. There was 1 adenocarcinoma of colon (mirikizumab group) and no deaths during the treatment period.

Conclusion

Efficacy and safety profiles were consistent with LUCENT-1 overall population, supporting benefits of mirikizumab treatment in the Chinese UC patients.

Disclosure

No conflict of interest to disclose