Introduction

Delayed bleeding (DB) is a possible adverse event following gastric endoscopic submucosal dissection (ESD). The Bleeding after ESD Trend from Japan (BEST-J) score was created as a risk prediction model for DB following gastric ESD, but is yet to be validated in non-Asiatic populations.

Aims & Methods

We aimed to apply and validate the BEST-J score on a European sample.
We have conducted a longitudinal study of all consecutive patients undergoing gastric ESD on a European Endoscopic Unit. DB was defined as a hemorrhage with clinical symptoms and confirmed by emergency endoscopy from the time of completion of ESD to 28 days after ESD.
BEST-J score (use of vitamin K antagonists +4, direct oral anticoagulants +4, aspirin or P2Y12R antagonists +2; withdrawing antithrombotic drugs -1; chronic kidney disease +3; multiple lesions +1; lesion ≥30mm +1; lesion in lower-third of the stomach +1) was calculated in each patient and confronted with the outcome (DB).

Results

Final sample included 161 patients, 102 (63.4%) male, with a mean age of 68±8 years. From these, 10 (6.2%) presented DB following ESD, with a median time to bleeding of 7 days (IQR 6.8).
According to BEST-J score, bleeding risk was low (0-1 points) in 111 (68.9%), intermediate (2 points) in 29 (18.0%), high (3-4 points) in 16 (9.9%) and very high (≥5 points) in 5 (3.1%) patients.
BEST-J score presented an excellent accuracy predicting DB in our sample, with an AUC=0.907 (95%CI=0.801-1.000; p<0.001). The optimal cut-off value to predict DB was a BEST-J score ≥3, which matches the cut-off value for high-risk of bleeding in the original investigation. This value had a sensitivity of 90% and specificity of 92%.

Conclusion

The BEST-J score still presents excellent accuracy in risk stratification for post-ESD bleeding in European individuals. Thus, this score may help to guide which patients benefit the most from prophylactic therapies following gastric ESD in this setting.

Clinical Case Summary

A 78-year-old female with personal history of ischemic cardiomyopathy and atrial fibrillation was referred to a tertiary center due to iron deficiency anemia without clinical evidence of gastrointestinal bleeding. The patient required periodic erythrocyte transfusion and intravenous iron treatment. An upper and lower endoscopy was performed, yielding unremarkable findings.
In this context, the patient underwent capsule endoscopy which revealed an ileal polypoid ulcerated lesion close to a Meckel diverticulum. Subsequently, a double balloon retrograde enteroscopy was performed, with identification of a Meckel diverticulum without ulcers nor active bleeding. Furthermore, a 15-millimeter diameter polypoid lesion was also seen and removed using a diathermic snare after submucosa injection, clip and loop application. The histopathological report confirmed a pyogenic granuloma, also known as lobular capillary hemangioma. After lesion removal the patient experienced anemia resolution.
Pyogenic granuloma is a rare benign proliferation of capillary vessels, most commonly affecting the skin and oral mucosa, characterized by friable bright red papules. Nevertheless, gastrointestinal involvement can also occur. The high vascularization associated with these lesions justifies the presence of iron deficiency anemia due to gastrointestinal losses. This case highlights a rare small bowel pyogenic granuloma. Despite its association with iron deficiency anemia, the occurrence of a pyogenic granuloma in this context, particularly in the enteric mucosa, is uncommon. Nevertheless, recent studies suggest that this clinical entity may be underdiagnosed due to improper identification of inflammatory or hyperplastic polyps. Capsule endoscopy and device assisted enteroscopy were crucial in localizing and ensuring proper therapeutic management of this lesion, thereby solving the iron deficiency anemia.

References

1. Capsule endoscopy images with identification of the Meckel diverticulum and pyogenic granuloma
2. Device-assisted enteroscopy images with identification of the Meckel diverticulum and pyogenic granuloma
3. Histopathological sample of pyogenic granuloma

Clinical Case Summary

A 47-year-old female with a one-year history of ulcerative colitis (UC) presented with painful red skin lesions on her wrists and anterior tibiae, which progressed to necrotic ulcers (1). Initial treatment for her UC was mesalamine; however, she experienced three steroid-dependent flares. Prior to the initiation of infliximab for luminal disease activity, these progressive necrotic ulcers developed. Physical examination revealed deep, irregularly bordered, necrotic-based ulcerative lesions with erythematous rims. Bilateral pulses were palpable, and mucous membranes were normal. There was no history of animal exposure or recent travel. Elevated C-reactive protein (9 mg/L, ref: 0-5 mg/L) and negative procalcitonin were noted; other tests, including rheumatoid factor, antinuclear antibody, antineutrophil cytoplasmic antibody, viral serology, and deep tissue cultures for microorganisms, were unremarkable. A skin biopsy demonstrated a necrotic epidermis and neutrophilic infiltrates, consistent with suspected pyoderma gangrenosum, which was supported by a colonoscopy showing Mayo 3 active UC. The tuberculin skin test was negative. Infliximab was initiated, resulting in an intestinal response but only a partial response of the skin lesions (2). Topical tacrolimus ointment was added. Following the infliximab induction regimen, limited improvement in the skin lesions prompted the addition of systemic corticosteroids. After two weeks, a partial response persisted, and prednisolone was tapered. Infliximab was discontinued, and ustekinumab therapy combined with hyperbaric oxygen therapy was initiated, leading to significant regression of the skin lesions starting from the tenth day (3). This case illustrates refractory pyoderma gangrenosum in ulcerative colitis with a limited response to initial anti-tumor necrosis factor therapy, highlighting the potential of interleukin-23 pathway inhibition for managing this extra-intestinal manifestation.

References

References of illustrative material:
1. Clinical Photograph of Initial Wrist Lesions: Demonstrates the early presentation of pyoderma gangrenosum as erythematous and painful lesions on the patient's wrists upon initial presentation.
2. Clinical Photograph of Refractory Tibial Ulcers: Shows the characteristic deep, necrotic, and irregularly bordered ulcers on the patient's anterior tibiae, highlighting the severity and refractory nature of the pyoderma gangrenosum despite initial treatment.
3. Clinical Photograph of Post-Treatment Improvement: Illustrates the significant regression of the skin ulcers on the patient's tibiae following the initiation of ustekinumab and hyperbaric oxygen therapy, demonstrating the positive outcome of the alternative treatment strategy.

Introduction

Steatotic liver disease (SLD) encompasses a spectrum of conditions, including metabolic dysfunction-associated SLD (MASLD), alcohol-related liver disease (ALD), and the overlapping category of MetALD. SLD affects more than a third of adults globally, but the majority remain undiagnosed, partially due to its lack of symptoms and limited awareness among patients and physicians. Adults undergoing screening colonoscopy, typically aged ≥50 years, represent a key population for targeted SLD detection, as they have a higher prevalence of cardiometabolic risk factors and is already engaged with preventive healthcare.

Aims & Methods

We examined 610 consecutive individuals aged ≥50 years with no known history of chronic liver disease who were referred for a colonoscopy for colorectal cancer screening. The protocol included sonographic assessment of liver steatosis and point shear wave elastography (pSWE) for liver fibrosis quantification, anthropometric measurements, biochemistry, medical history and alcohol intake evaluation. From the collected data, non-invasive fibrosis scores were calculated and used for aetiological and risk stratification.

Results

A total of 543 patients were included in the final analysis, after excluding patients with an invalid pSWE measurement (5.3%, n=29) and then excluding patients with incomplete results (n=38). The median age was 64 years (IQR 57-70) and 54.0% were male. The median BMI was 28.7 kg/m² (IQR 25.8–31.4) in males and 28.3 kg/m² (IQR 24.2-31.5) in females. SLD was identified in 63.4 % (n=344) of participants. Elevated liver stiffness (pSWE ≥ 1.30 m/s) was found in 26.9 % (n=146), and 4.8% (n=26) had values ≥1.70 m/s, suggestive of compensated advanced chronic liver disease. Among patients with pSWE ≥ 1.30 m/s, MASLD was the predominant aetiology (69.9%, n=102), followed by MetALD (15.8%, n=23), ALD (1.4%, n=2), cryptogenic (11.6%, n=17) and other etiologies (1.4%, n=2). Preselection using EASL-EASD-EASO criteria (i.e. presence of type 2 diabetes or central obesity plus ≥1 cardiometabolic risk factor and elevated liver enzymes) would have detected 365 at-risk individuals (67.2% of the cohort) of whom 55.9% (n=204) had a FIB-4 index ≥1.30. This approach would have identified only 30.4% (n=38) of all the patients with MASLD/MetALD with elevated liver stiffness (n=125).

Conclusion

Opportunistic screening for SLD in patients undergoing screening colonoscopy could be a useful strategy for detecting asymptomatic and potentially progressive liver disease. This approach identified a high prevalence of SLD (63.4%) and elevated liver stiffness (26.9%) in this population, primarily due to MASLD and MetALD. The integration of ultrasound and elastography added minimal burden to the existing workflow while enabling early risk stratification without the need for additional patient visits or referrals.

References

1 Tacke F, Horn P, Wong VWS, Ratziu V, Bugianesi E, Francque S, et al. EASL–EASD–EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). Journal of Hepatology [Internet]. 2024 Jun 7;81(3):492–542.
2 Lazarus JV, Miralles-Sanchez JE, Agirre-Garrido L, Brachowicz N, Nicolàs A, Armenta A, et al. A call to action to address the steatotic liver disease public health threat in Barcelona. The Lancet Regional Health - Europe [Internet]. 2025 Mar 22;52:101272.
3 Barr RG, Wilson SR, Rubens D, Garcia-Tsao G, Ferraioli G. Update to the Society of Radiologists in Ultrasound Liver Elastography Consensus Statement. Radiology [Internet]. 2020 Jun 9;296(2):263–74.

Introduction

ESSENCE (NCT04822181) is an ongoing 247-week Phase 3, randomised, placebo-controlled trial evaluating the effect of the glucagon-like peptide-1 analogue, semaglutide 2.4 mg subcutaneous once weekly (OW) in participants with non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH). We report the baseline characteristics of the randomised participants.

Aims & Methods

Following a 14-week screening phase, 800 participants (part 1) of 1200 planned (part 2) with MASH and fibrosis stages 2/3 (F2/F3) were randomised 2:1 to receive semaglutide 2.4 mg subcutaneous OW or placebo OW added to standard of care. In part 1, the two primary endpoints at 72 weeks are resolution of steatohepatitis and no worsening of liver fibrosis, and improvement in liver fibrosis and no worsening of steatohepatitis. Based on a central pathologist evaluation, inclusion criteria were histological presence of steatohepatitis stages F2/F3 per the Nonalcoholic Steatohepatitis Clinical Research Network classification, and a non-alcoholic fatty liver disease activity score (NAS) of ≥ 4, with a score of ≥ 1 in steatosis, lobular inflammation and hepatocyte ballooning.

Results

800 participants (250 F2; 550 F3) were randomised. Mean (SD) age was 56 (11.6) years; 57.1% were female; ≥ 99% had ≥ 1 cardiometabolic risk factor(s) in accordance with the metabolic dysfunction-associated steatotic liver disease (MASLD) definition. Mean (SD) NAS was 5.05 (0.95), and higher in F3 versus F2 (5.11 [0.95] vs 4.92 [0.93], respectively). Notably, participants with a higher NAS had more cardiometabolic risk factors for MASLD (52.9% with NAS ≥ 5 vs 45.3% with NAS 4). Similarly, a greater proportion of participants with F3 had all five cardiometabolic risk factors versus F2 (52.9% vs 44.8%, respectively). Although cardiometabolic comorbidities were highly prevalent, 44.5% of participants did not have type 2 diabetes (T2D), and 27.3% did not have obesity. Normal liver transaminases were observed in 26.3% of participants (28% F2; 26% F3). Mean (SD) FibroScan liver stiffness was 12.8 (6.9) kPa, and values of < 8 kPa were observed in 15.3% of participants. Mean (SD) controlled attenuation parameter value was 329 (46) dB/m; mean (SD) enhanced liver fibrosis (ELF) score was 10.0 (1.0), and 43.5% of participants had an ELF score of < 9.8. Overall, 8.8% and 9.0% of participants with/without T2D did not meet any of the following non-invasive criteria: Fibrosis-4 index ≥ 1.3, vibration-controlled transient elastography ≥ 8.1, or ELF ≥ 9.8, and more participants with F2 (14.7–16.4%) did not meet these criteria versus F3 (4.5–6.7%).

Conclusion

The ESSENCE baseline population includes participants with significant fibrosis (F2 and F3) and approximately 91% of the trial population had ≥ 1 positive diagnostic non-invasive test. Cardiometabolic risk factors were found in ≥ 99% of participants, and in increased numbers in those with higher NAS and fibrosis stages.
This is an encore of an abstract that will be presented for the first time at the European Association for the Study of the Liver (EASL) Congress, 5–8 June 2024, Milan, Italy.

Disclosure

The ESSENCE trial is funded by Novo Nordisk A/S.
PNN: reports grants from Novo Nordisk, and has received consulting fees from Novo Nordisk, Boehringer Ingelheim, Gilead, Intercept, Poxel Pharmaceuticals, Bristol Myers Squibb (BMS), Pfizer, Sun Pharma, Madrigal and GSK. PNN also reports honoraria as a speaker for Novo Nordisk and AiCME; support for attending meetings for Novo Nordisk; and participation on an advisory board for Novo Nordisk, Boehringer Ingelheim, Gilead, Intercept, Poxel Pharmaceuticals, BMS, Pfizer, Sun Pharma, Madrigal and GSK.
EB: served as a consultant or advisory board member for Boehringer Ingelheim, Gilead, Intercept, Merck, Novo Nordisk, Pfizer, ProSciento, and as a speaker for Gilead, Intercept, Merck, Novo Nordisk and Pfizer. EB has also received a research grant from Gilead for fatty liver research.
VR: received consulting fees from Novo Nordisk, Sagimet, Madrigal, Enyo, Poxel, Northsea, Intercept and ProSciento, and research grants (to institution) from Gilead and Intercept.
MER: consults for Boehringer Ingelheim, CytoDyn, GSK, Novo Nordisk, HistoIndex, Intercept, Madrigal, NGM Bio and Sonic Incytes.
MR: reports grants from Boehringer Ingelheim and Novo Nordisk, and has received fees for consulting or participation in advisory boards for Boehringer Ingelheim, Echosens, Eli Lilly and Novo Nordisk. MR also reports honoraria as a speaker for AstraZeneca, Boehringer Ingelheim, Novo Nordisk and Madrigal.
AJS: consults for and advises Avant Santé and AstraZeneca. AJS also consults for and has received grants from Akero, BMS, Intercept, Eli Lilly, Madrigal and Novo Nordisk. AJS consults for and owns stock in Rivus, and also consults for AGED Diagnostics, Albireo, Alnylam, Altimmune, Boehringer Ingelheim, 89Bio, Echosens, Genentech, Gilead, GSK, HistoIndex, Mallinckrodt, Merck, NGM Bio, Novartis, PathAI, Pfizer, Poxel, Regeneron, Salix, Siemens, Surrozen, Takeda, Terns and Zydus. AJS owns stock in Durect, Exalenz, Genfit, Indalo, Inversago and Tiziana, and has received royalties from Elsevier and Wolters Kluwer.
KAE, IK, LHØ, DV and JZ: employees and stockholders of Novo Nordisk A/S.

Introduction

With about 40% of adults infected with Helicobacter pylori (H. pylori), China has the highest number of gastric cancer (GC) cases worldwide.¹ Household transmission is the primary route for H. pylori infection,² and family-based testing and treatment has been proposed to mitigate GC cancer risk and prevent transmission.^1,3,4 A household-based transmission model for H. pylori would enhance understanding of H. pylori dynamics and inform intervention strategies. However, few models⁵ have been developed for H. pylori, and none incorporates household transmission.

Aims & Methods

We developed an agent-based household transmission model for H. pylori in China to study transmission patterns from 1990 to 2021. Building on our previous modeling framework,⁶ the model includes demographic and transmission components. The demographic simulation captures births, deaths, marriages, and mobility among youth, couples, and the elderly. Mobility parameters were calibrated using joint distributions of household size and generation from Chinese censuses of 1990, 2000, 2010, and 2020, allowing realistic household dynamics in China. In the transmission simulation, household and community transmissions were modeled using a susceptible-infected structure, applying density-dependent transmission within households and frequency-dependent transmission in the community. Contact rates, defined as the number of contacts adequate for transmission by an individual per year, were allowed to vary over time, and were dependent on the susceptible individual’s age. Contact rate variation was modeled by adjusting base rates with age- and year-specific multipliers, each following a continuously decreasing function. Simulations began in 1900, with the first 90 years as a burn-in period. Transmission parameters were calibrated and validated using data from our meta-analyses and a large national family-based survey from China in 2021⁷.

Results

The model aligned well with calibration targets. Key parameters and calibration results are summarized in the Table. Consistent with observed data, larger households had higher infection rates than smaller households. Three-generation households were more likely to have infected members than one- or two-generation households. Model calibration showed best fit when the within-household contact rate (0.2) was higher than the community rate (0.1), and when most infections occurred before age 20. Validation confirmed model accuracy: children’s infection probabilities were 31% with both parents infected, 21% with one infected parent, and 9% with neither. Our model found that family clustering became more pronounced in recent years with lower prevalence compared to earlier periods with higher prevalence.

Table. Calibration and validation results for the transmission model

Conclusion

We developed a novel agent-based model simulating community and household transmission of H. pylori. Our results confirm that household transmission is the primary infection route, and that childhood is the predominant period of acquisition. Notably, family clustering becomes more prominent in low-prevalence contexts. This model provides a valuable tool for evaluating various control strategies and offers insights difficult to obtain in real-world data. Future extensions could incorporate antibiotic resistance dynamics and adapt the model to other country contexts.

References

1. Ding, S.-Z. et al. Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition). Gut 71, 238–253 (2022).
2. Malfertheiner, P. et al. Helicobacter pylori infection. Nat. Rev. Dis. Primer 9, 1–24 (2023).
3. Chey, W. D. et al. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Off. J. Am. Coll. Gastroenterol. ACG 119, 1730 (2024).
4. Shah, S. C., Wang, A. Y., Wallace, M. B. & Hwang, J. H. AGA Clinical Practice Update on Screening and Surveillance in Individuals at Increased Risk for Gastric Cancer in the United States: Expert Review. Gastroenterology 168, 405-416.e1 (2025).
5. Rupnow, M. F. T., Shachter, R. D., Owens, D. K. & Parsonnet, J. A Dynamic Transmission Model for Predicting Trends in Helicobacter pylori and Associated Diseases in the United States. Emerg. Infect. Dis. 6, 228–237 (2000).
6. Blok, D. J. et al. The long-term impact of the Leprosy Post-Exposure Prophylaxis (LPEP) program on leprosy incidence: A modelling study. PLoS Negl. Trop. Dis. 15, e0009279 (2021).
7. Zhou, X.-Z. et al. Large-scale, national, family-based epidemiological study on Helicobacter pylori infection in China: the time to change practice for related disease prevention. Gut 72, 855–869 (2023).B1