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

Introduction

In recent years, there has been increased focus on appropriate proton pump inhibitor (PPI) prescribing due to the growing awareness of the prevalence of long-term PPI use globally.1 Rebound acid hypersecretion (RAHS) has been described as potentially contributing to PPI overuse and treatment dependence1 . RAHS is a physiological phenomenon observed following PPI discontinuation after a minimum of 4 – 8-week use. However – despite being first described in 1996 – its clinical relevance, underlying mechanisms, prevalence, and impact on patient outcomes are still not completely understood.

Aims & Methods

The purpose of this rapid review is to assess the current evidence published on RAHS, the potential mechanisms behind the phenomenon, its prevalence and clinical significance in patients discontinuing PPI therapy.
A rapid review of peer-reviewed literature was conducted through Embase and PubMed. Systematic reviews and clinical studies were included if they examined RAHS, reported prevalence, or evaluated patient-reported symptoms post-PPI withdrawal. Key findings were extracted and summarised across three domains: physiological mechanisms, prevalence and severity, and patient impact.

Results

A total of 272 articles – published between 2005 and 2024 – were retrieved, with 7 articles meeting the inclusion criteria for final review. Five of these were clinical studies, whilst the remaining 2 were systematic literature reviews. All, except 1, of the studies included were conducted more than 10 years ago – 3 randomised controlled trials, 1 cross sectional study, and 1 study looked at pre-surgery patients without randomisation. The studies were heterogeneous in design, the study populations varied broadly between 7 and 150 participants, and the prevalence data appeared to be inconsistent. Studies show a physiological basis for RAHS, including upregulation of gastrin and enterochromaffin-like cell hyperplasia, during PPI therapy, leading to transient acid hypersecretion upon PPI withdrawal^2,3,4,5. Symptoms resembling dyspepsia or gastro-oesophageal reflux disease (GORD) recurrence were commonly reported in both healthy volunteers and patients^2,3,6,7. RAHS was transient in most cases^2,3,4 but may drive long-term PPI use due to misinterpretation of symptoms as disease recurrence. However, a small number of studies reviewed in the two systematic literature review papers challenged the existence of clinically meaningful RAHS, particularly after short-term or low-dose therapy^6,8.

Conclusion

There is growing evidence that RAHS is a physiologically plausible and clinically relevant phenomenon in long-term PPI users. It is suggested that RAHS may contribute to symptom recurrence and therapy dependence, resulting in the continuation of unnecessary PPI therapy. With the increasing efforts on PPI deprescribing due to growing concerns over long-term use when there’s a lack of appropriate indication, clinicians need to be aware of the potential for RAHS to act as a roadblock for patients. However, despite discussion about RAHS ongoing for almost 30 years, there is still limited understanding about its impact on patients and the potential contribution to the challenges of PPI deprescription. Most importantly, there’s limited understanding of appropriate management solutions to overcome these challenges. In order to improve education for both clinicians and patients, further research is required on appropriate management solutions for RAHS and to aid PPI deprescribing efforts.

References

1. Savarino E et al., Holistic management of symptomatic reflux: rising to the challenge of proton pump inhibitor overuse. Br J Gen Pract. 2022; 72(724):541-544.
2. Reimer C at el., Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology. 2009; 137(1):80-7, 87.e1.
3. Niklasson A et al., Dyspeptic symptom development after discontinuation of a proton pump inhibitor: a double-blind placebo-controlled trial. Am J Gastroenterol. 2010;105(7):1531-7.
4. Fossmark R et al., Rebound acid hypersecretion after long-term inhibition of gastric acid secretion. Aliment Pharmacol Ther. 2005; 21(2):149-54.
5. Helgadóttir H et al., The effects of long-term therapy with proton pump inhibitors on meal stimulated gastrin. Dig Liver Dis. 2014; 46(2):125-30.
6. Lødrup AB et al., Systematic review: symptoms of rebound acid hypersecretion following proton pump inhibitor treatment. Scand J Gastroenterol. 2013; 48(5):515-22.
7. Vales A et al., Randomised clinical trial: the use of alginates during preinvestigation proton pump inhibitor wash-out and their impact on compliance and symptom burden. BMJ Open Gastroenterol. 2023; 10(1):e001026.
8. Hunfeld NG et al., Systematic review: Rebound acid hypersecretion after therapy with proton pump inhibitors. Aliment Pharmacol Ther. 2007 Jan 1;25(1):39-46.

Disclosure

Clinical Case Summary

Autoimmune gastritis (AIG) is an immune-mediated disease characterized by destruction of gastric parietal cells, which leads to the loss of internal factor Casl and decreased production of hydrochloric acid. When conducting endoscopic examination, it is possible to visualize a specific picture of the gastric body mucosa: diffuse atrophy, revealing changes occurring on the background of long-term hypergastrinemia.
Female patient, 45 years old, complaining of increased gas formation, burning sensation and heaviness in the epigastrium after eating, air burping. Chronic diseases: chronic iron deficiency anemia, B12 deficiency, autoimmune thyroiditis. Notes restriction of eating red meat, which causes heaviness in the abdomen. Heredity for cancer is not aggravated. Esophagogastroduodenoscopy revealed pallor of the mucous membrane of the stomach body, single islets of preserved mucous membrane of the stomach body, presence of multiple point whitish inclusions (WGA - white globe appearance) on all walls, forming the effect of “stardust”.
The diagnosis of autoimmune atrophic gastritis was confirmed by laboratory tests: Gastrin dated 01/20/2024 - 746 pg/mL, Chromogranin A CgA dated 01/2024 - 150.4 ng/mL, antibodies to gastric parietal cells -2560. Gastropanel from 20.01.2024 - gastrin-17 baseline > 30.6 pmol/l; pepsinogen I 21.89 µg/l; pepsinogen II 11.80 µg/l, pepsinogen I/II ratio - 1.9. 13C-urease breath test for HP dated 01.2024 - 1.3. Antibodies to Helicobacter, IgG < 13. Histologic conclusion: Moderate atrophy of the gastric body mucosa with the presence of cystic-expanded glands filled with opaque content.
The “stardust” phenomenon was first described in a case of long-term administration of potassium-competitive hydrochloric acid blockers. Given that elevated gastrin levels always accompany AIG, detection of this phenomenon is also possible in cases of AIG.The present case is the first description of the "stardust" phenomenon in a patient with autoimmune gastritis.

References

"Propensity score matching analysis: incidence and risk factors for "stardust" gastric mucosa, a novel gastric finding potentially induced by vonoprazan" Tetsuya Yoshizaki et al. DOI: 10.1111/apt.16151
https://pubmed.ncbi.nlm.nih.gov/33159407/

Disclosure

Yes

Introduction

Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract often complicated by intestinal strictures. Accurate differentiation between inflammatory and fibrotic strictures is essential for guiding therapeutic strategies but remains challenging with current diagnostic tools. The capability of greyscale intestinal ultrasound (IUS) alone for characterizing inflammation versus fibrosis in CD strictures is not accurate enough to be used in clinical practice. This study investigates the diagnostic utility of advanced ultrasound techniques, including shear wave elastography (SWE), MV-Flow Doppler, and the Limberg score (LS), in the evaluation of strictures in patients with CD.

Aims & Methods

A prospective cross-sectional study enrolled 15 consecutive patients with ileal and ileocolonic CD scheduled for surgery due to symptomatic strictures. Each patient underwent intestinal ultrasound, including SWE, MV-Flow Doppler imaging, and LS assessment of the stenotic segment, within one week before surgery. Histopathological analysis of resected bowel specimens was then performed to grade inflammation and fibrosis according to a semiquantitative scoring system. Statistical analysis evaluated the correlation between ultrasound parameters and histological findings.

Results

SWE reliably differentiated fibrotic grades, with mean stiffness values significantly increasing from mild to severe fibrosis (P = 0.014). A cutoff of 24.85 kPa distinguished mild from moderate/severe fibrosis with 83.33% sensitivity and 88.89% specificity (AUC = 0.944). Conversely, SWE did not significantly distinguish between grades of inflammation (P = 0.643). MV-Flow Doppler values strongly correlated with histological inflammation grades (P = 0.007), with mean microvascular percentages increasing from 8.1% (mild inflammation) to 36.2% (severe inflammation). The LS also demonstrated high diagnostic accuracy for severe inflammation (AUC = 0.910, sensitivity 80.0%, specificity 90.0%).

Conclusion

This study underscores the complementary roles of SWE, MV-Flow, and LS in characterizing strictures in CD. SWE excels in assessing fibrosis, while MV-Flow and LS provide sensitive measures of inflammation. The integration of these modalities with conventional greyscale IUS offers a comprehensive and non-invasive approach to optimize diagnosis and management of CD strictures. Future research should validate these findings in larger, multicenter studies and explore their longitudinal applications.