Introduction

Screening programmes for gastric cancer are currently being researched in Europe as part of the TOwards GAstric Cancer Screening Implementation (TOGAS) project (1). A ‘screen & treat’ approach for Helicobacter pylori (H. pylori), is one such strategy being assessed as part of a primary preventative measure. In order for such a programme to be viable, the availability of an effective treatment is paramount. Given the rising rates of antimicrobial resistance worldwide, careful consideration must be given to prescribing first-line treatment with the highest efficacy. This interim report evaluates key performance measures in the treatment of H. pylori within the Irish arm – representing the Western European cohort - of the TOGAS pilot screening programme.

Aims & Methods

This interim data evaluates the efficacy of 10-day treatment with single capsule combination therapy: Bismuth subcitrate 140mg/Metronidazole 125mg/Tetracycline 125mg, three tablets, four times daily (PYLERA, Juvise pharmaceuticals) with a high-dose proton pump inhibitor (Esomeprazole 40mg twice daily).
Secondary outcome measures include;

1. Treatment acceptance rate
2. Side-effect profile
3. Adverse events

3030 individuals aged 30-34 years were invited to undergo screening for H. pylori through their general practitioner or workplace in the period January 24-March 25. Those who tested positive on both serology (BIOHIT H. pylori IgG antibody) and 13-C urea breath test (IR Force 200, Richen Medical) were offered treatment. Treatment consisted of 10-day combination therapy (PYLERA) and a high-dose proton pump inhibitor (PPI). Eradication confirmation with a 13-C UBT was offered a minimum of 6 weeks post-treatment. Demographics, risk factors for infection, treatment effectiveness and side effect profile were recorded. Stata was used for statistical analysis. χ² test was used for comparison of categorical variables (significance level p<0.05).

Results

464 asymptomatic individuals were enrolled. The median age was 32; 48%(n=223) were male. 11%(n=50) tested positive on both serology and 13-C UBT. Those who tested positive were more likely to be male [64%] (p < 0.02), a history of current or previous smoking was found to be nonsignificant (34%, p <0.9). 96%(n=48) of positive participants consented to treatment; 2 were excluded from receiving treatment due to pregnancy. Among those treated, 96% (44/46) reported adherence rates of >90%. In those reporting compliance rates <90 %, side effect profile was the leading cause of non-compliance. Side effects were reported by 24% (11/46) of participants. These were predominantly gastrointestinal side effects and reported as mild-moderate in severity, 6% discontinued treatment on account of them (n=3). All symptoms resolved after cessation. No serious adverse events occurred. Post-treatment, a 13-C UBT was completed in 80% (n=37) of treated individuals. Eradication rates were 97% (36/37) in the per-protocol group and 89% (33/37) in the intention-to-treat group. Treatment discontinuation due to side effects was the leading cause of treatment ‘failure’. In those requiring 2^nd line therapy (n=4), levofloxacin-based quadruple therapy was found to be successful in 66%(2/3) of those who completed eradication follow-up.

Conclusion

Single capsule combination therapy and high-dose PPI achieved eradication rates of >90% in the per-protocol group. No serious adverse events occurred secondary to treatment. These interim results indicate that 10-day combination therapy serves as an effective first-line therapy for future population-based screening programmes in a European population.

References

1. Commission E. TOGAS - Towards Gastric Cancer Screening Implementation in the European Union: European Commission; 2023 [Available from: https://health.ec.europa.eu/non-communicable-diseases/cancer/europes-beating-cancer-plan-eu4health-financed-projects/projects/togas_en.

Disclosure

Dr. Deane reports receipt of research funding support from EU4 Health grant GA number: 101101252. Juvise pharmaceuticals provided PYLERA for this branch of the study.

Introduction

The urea breath test (UBT) is the clinic's most popular and accurate non-invasive diagnostic method for H. pylori infection. Yet, it is time-consuming and unavailable to some individuals. The oral rapid urease test (RUT) is an emerging non-invasive convenience method but lacks clinical data support.

Aims & Methods

A double-center, double-blind, methodological comparative design experiment is invited to evaluate the consistency of the oral RUT with UBT. 247 participants were enrolled. Their Dental plaque and tongue coating samples were collected, blind and tested with RUT.

Results

The significant association between the RUT and UBT was analyzed.A total of 247 participants were included in the study. The oral RUT showed a high level of agreement with the UBT. The sensitivity of the test reagent was 98.63% (95% CI: 92.64%, 99.76%), and the specificity was 96.34% (95% CI: 92.25%, 98.31%). The overall conformity rate was 97.05% (95% CI: 94.03%, 98.56%). The positive predictive value was 92.31%, and the negative predictive value was 99.37%. The positive likelihood ratio was 26.96, and the negative likelihood ratio was 0.01. The Kappa value was 0.97.

Conclusion

The efficacy of oral RUT for Helicobacter pylori infection diagnosis is extremely consistent with the UBT.

Introduction

Gastrointestinal (GI) hemorrhage accounts for 30% of acute decompensations in cirrhotic patients, with 60% originating from variceal bleeding. Each decompensation episode carries an in-hospital mortality rate of 13%, and a 6-week mortality rate of 20%, commonly assed using Child Pugh (CP) and MELD scores. The ALBI (Albumin-Bilirubin) score, which includes only two variables, offers a simplified evaluation of liver function. However, there is limited data on its utility in predicting short-term mortality in cirrhotic patients with GI hemorrhage.

Aims & Methods

This study aimed to evaluate the association between ALBI Score with short-term mortality in cirrhotic patients with GI hemorrhage. We conducted a prospective, cross-sectional study between January and December of 2023 at Hospital Roosevelt, Guatemala, including cirrhotic patients admitted for GI hemorrhage. Informed consent was obtained from all participants. Categorical variables were analyzed using the chi-square test, normally distributed continuous variables with Student’s t-test, and non-normally distributed variables with the Mann-Whitney U test. Logistic binary regression and AUROC analysis were used to assess associations with short-term mortality. Statistical analyses were performed using SPSS.

Results

A total of 187 patients were included: 50.8% female and 49.2% male, with a mean age of 56 among survivors and 58 among non-survivors. Of these, 52.9% had a prior diagnosis of cirrhosis, while 47.1% were newly diagnosed. Cirrhosis etiology was metabolic in 50.2%, alcoholic in 42.7%, autoimmune in 4.3%, HCV in 1.6%, and HBV in 1.1%. At admission, 80.8% had no ascites and 97.3% had no hepatic encephalopathy. he causes of GI hemorrhage were 86.1% esophageal varices, 3.2% gastric varices, 9.1% gastric ulcers, and 1.6% esophagitis.
Non-survivors had significantly lower systolic blood pressure (93.90 ± 16.3 mmHg vs. 107.92 ± 17.4 mmHg; p = 0.002) and mean arterial pressure (69.50 ± 14.5 mmHg vs. 79.67 ± 11.7 mmHg; p = 0.005) compared to survivors. Non-survivors exhibited significantly higher INR (1.79 ± 0.56 vs. 1.52 ± 0.41; p = 0.026) and total bilirubin (5.85 ± 8.73 mg/dL vs. 2.02 ± 2.82 mg/dL; p = 0.031), and lower serum albumin levels (2.40 ± 0.43 g/dL vs. 3.10 ± 0.54 g/dL; p < 0.001).

Prognostic scores were significantly higher among non-survivors: MELD (19.25 ± 10.09 vs. 13.57 ± 5.47; p = 0.002), MELD-Na (20.35 ± 9.76 vs. 14.44 ± 6.42; p = 0.002), Child-Pugh (9.15 ± 2.21 vs. 7.18 ± 1.90; p < 0.001), and ALBI score (-0.96 ± 0.51 vs. -1.76 ± 0.58; p < 0.001). Additionally, the length of hospital stay was significantly shorter among non-survivors (3.90 ± 3.82 days) compared to survivors (6.59 ± 5.58 days; p = 0.001).

Scores	Mortality In-Hospital	Mortality at 4 weeks	Mortality at 6 weeks
ALBI	AUC: 0.850 95% CI (0.780 - 0.921) p: 0.000	AUC: 0.881 95% CI (0.823 - 0.938) p: 0.000	AUC: 0.867 95% CI (0.806 - 0.927) p: 0.000
Child Pugh (CP)	AUC: 0.762 95% CI (0.668 - 0.857) p: 0.000	AUC: 0.819 95% CI (0.739 - 0.900) p: 0.000	AUC: 0.805 95% CI (0.728 - 0.881) p: 0.000
MELD	AUC: 0.714 95% CI (0.606 - 0.822) p: 0.002	AUC: 0.785 95% CI (0.693 - 0.878) p: 0.000	AUC: 0.786 95% CI (0.700 - 0.871) p: 0.000
MELD-Na	AUC: 0.711 95% CI (0.599 - 0.823) p: 0.002	AUC: 0.778 95% CI (0.683 - 0.873) p: 0.000	AUC: 0.783 95% CI (0.696 - 0.870) p: 0.000

Multivariable analysis showed that:

• Higher ALBI score was significantly associated with mortality (Risk Ratio 25.80; 95% CI: 6.75–98.67; p < 0.001),
• Hospital stay <5 days (RR 9.91; 95% CI: 2.07–47.47; p = 0.004),
• Endoscopy performed within 12 hours (RR 7.53; 95% CI: 2.01–28.15; p = 0.003).

Conclusion

The ALBI score outperforms CP and MELD scores in predicting short-term mortality (in-hospital, 4 weeks, and 6 weeks) in cirrhotic patients with GI hemorrhage. Observed mortality was 10% in-hospital, 13% at 4 weeks, and 16% at 6 weeks.

Introduction

Anti-mitochondrial antibodies (AMA) are commonly associated with Primary Biliary Cholangitis (PBC), a progressive liver disease. However, the clinical significance of AMA positivity in patients with normal liver enzymes remains poorly understood. Despite the presence of AMA, many patients maintain normal liver function, raising the question of whether these individuals are at risk for developing liver-related complications.

Aims & Methods

This study aims to evaluate the natural history, prognostic implications, and potential risk factors for disease progression in AMA-positive patients with normal liver enzymes.
A retrospective cohort study was conducted using a national healthcare database to identify patients (aged>18) with a positive AMA and normal liver enzymes between 2002 and 2023. Demographics, biochemical parameters, and liver-related complications were analyzed. Multivariate regression models assessed predictors of disease progression.

Results

Among 1,018 patients, 76 (7.5 %) developed Primary biliary cholangitis (PBC), and 30 (2.9%) progressed to cirrhosis over a median follow-up of 6.3 years. Liver-related complications were rare, with esophageal varices in 1.1%, ascites in 1.8%, hepatocellular carcinoma in 0.2%, and liver transplantation in 0.1%. Notably, higher AMA titers were strongly associated with increased risk of developing PBC, cirrhosis and liver-related complications, demonstrating a clear titer-dependent pattern.

Conclusion

Most AMA-positive patients with normal liver enzymes do not develop clinically significant liver disease. However, higher AMA titers identify a high-risk subgroup that warrants closer monitoring. These findings underscore the need for risk-stratified follow-up strategies and may influence future clinical guidelines.

Introduction

Colorectal cancer (CRC) is the most common cancer in Spain, with an estimated 44,573 new cases in 2025. The standard CRC screening strategy involves the immunological faecal occult blood test (FIT), followed by colonoscopy in positive cases. However, the low specificity of FIT results in a significant number of unnecessary colonoscopies, placing a high burden on healthcare systems. There is a growing need to explore alternative screening strategies that offer better cost-effectiveness ratios. The gut microbiota plays a key role in CRC carcinogenesis, and several bacterial species involved in this process have been identified. A diagnostic tool based on the combination of FIT (cut-off 100 ng/mL – FIT100) and a bacterial signature has been designed to detect CRC and advanced lesions (AL, defined as ≥1 cm and/or high-grade dysplasia and/or a hairy component). This tool uses qPCR to analyse the relative abundance of specific bacteria in the same stool sample used for FIT testing. Previous studies, including a proof-of-concept (N=172), confirmatory study (N=327), and clinical performance study (N=2,481), have validated the tool.

Aims & Methods

This study aims to evaluate the diagnostic performance of the bacterial signature applied to FIT100 positive participants and its potential to reduce unnecessary colonoscopies in the CRC screening program in Catalonia.
A prospective observational study was conducted in a multicentre cohort across five hospitals, including participants from the CRC screening program with a positive FIT100. Blinding was applied to the FIT, bacterial signature, colonoscopy, and biopsy. Colonoscopy-biopsy was used as the reference standard. The study included 1,453 participants, of which 48 were excluded from the analysis mainly because of poor sample conditions, resulting in a final sample of 1,405 participants. Sensitivity was defined as the proportion of true positives detected by the FIT that the bacterial signature also identifies as positive. Specificity was defined as the proportion of false positives of FIT that the bacterial signature correctly identifies as true negatives.

Results

From the 1,405 analysed cases, 44 were CRC, 472 AL, and 889 without AL. For CRC detection, the sensitivity was 95.5%, with a specificity of 18.4%. The reduction in false positives was 18.4%. For AL and CRC combined, the sensitivity was 82.6%, with a specificity of 18.4%.

Conclusion

The bacterial signature applied to FIT100 positive participants demonstrates high sensitivity for CRC detection while reducing unnecessary colonoscopies by minimizing false positives. Its implementation in the CRC screening protocol could improve the overall efficiency of the screening process. Future studies should focus on cost minimization and assess the tool's cost-effectiveness to ensure a favourable risk-benefit ratio for broader implementation.

Introduction

Post endoscopy upper gastrointestinal cancers (PEUGIC) are often missed opportunities to diagnose earlier or even prevent cancer. Up to 71% of PEUGIC are potentially avoidable, but identifying and investigating them can be challenging. A national process for identifying all PEUGIC in the English National Health Service and performing root cause analysis was developed.

Aims & Methods

Potential PEUGIC between 2017 and 2023 occurring 3-36 months after an index endoscopy which did not result in a cancer diagnosis were identified from National Cancer Registration Dataset and Hospital Episode Statistics held by the National Cancer Registration and Analysis Service. Data from local root cause analysis were uploaded onto a secure portal for national analysis. PEUGIC following surveillance endoscopies were excluded from this analysis. Logistic regression analysis was used to identify associations with outcomes of interest.

Results

3151 potential PEUGIC were examined by local reviewers in 144 English hospitals. 635 (20%) were excluded on local review and data were available for 2516 PEUGIC. 1897 (75.4%) PEUGIC followed diagnostic, follow-up or screening endoscopies. PEUGIC sites were oesophagus 61%, stomach 34% and duodenum 5%.
Table 1 shows the summary PEUGIC root cause results analysis based on the World Endoscopy Organisation categorisation. Categories C and D were associated with poor outcomes with 29% and 23% of cases receiving curative treatment, respectively. Compared to categories A and B receiving curative treatment in 53% and 37% of cases, respectively. Squamous cell cancers accounted for 37.5% of oesophageal PEUGIC and were associated with no lesion being detected (category C or D) in the PEUGIC segment OR 1.71 (95% CI 1.21-2.43).
Findings on index endoscopy (category A or B) at later oesophageal PEUGIC: pre-malignant lesion 23% (e.g. Barrett’s), cancer associated lesion 20% (e.g. ulcer) and other oesophageal focal lesions 15%. Findings on index endoscopy in gastric PEUGIC: cancer associated lesion 26%, pre-malignant lesion 7% and other gastric focal lesions 18%. 45% of the index endoscopies were classified as inadequate. Patient harm and adverse treatment outcomes were associated with an inadequate index endoscopy OR 1.56 (95% CI 1.28-1.91). The most common reason for inadequate endoscopy was inadequate management of lesions identified, which were most likely to be cancer associated lesions OR 1.43 (95% CI 1.11-1.69), specifically oesophageal strictures (24%) and gastric ulcers (23%).
Gastric diagnostic PEUGIC were diagnosed with more advanced cancer (40% stage 4 at diagnosis vs 30% oesophageal PEUGIC). Treatment following cancer diagnosis was adversely affected in 42% of PEUGIC. Reviewers considered that 57% of PEUGIC were at least possibly avoidable and 9% led to premature death.

Table 1 Root causes of all diagnostic PEUGIC

PEUGIC categorisation	Completed cases
A: Lesion detected, adequate assessment and decision making but PEUGIC occurred	595 (31%)
B: Lesion detected, inadequate assessment and decision making	522 (28%)
C: Possible missed lesion, endoscopy and decision making adequate	464 (24%)
D: Possible missed lesion, endoscopy and decision making inadequate	315 (17%)

Conclusion

Abnormalities in the area of the later cancer were detected at index endoscopy in 59% of PEUGIC. Inadequate lesion assessment, endoscopy and/or decision making was noted in 45% of PEUGIC, which adversely affected treatment outcome. Oesophageal squamous cell cancer was a common cause of PEUGIC, suggesting issues with lesion recognition in this cancer. Many patients had incurable disease when diagnosed and treatment was adversely affected in 42%.

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly referred to as non-alcoholic fatty liver disease (NAFLD), and dyslipidemia are among the most common metabolic disorders worldwide. Disruption of intestinal barrier integrity, as reflected by elevated zonulin levels, has been implicated in insulin resistance and lipid metabolism disorders, contributing to the pathogenesis of MASLD.

Aims & Methods

The aim was to evaluate fecal zonulin levels in patients with dyslipidemia and MASLD, and to explore their potential role as risk factors for disease development and progression. The study included 342 patients with dyslipidemia, among whom MASLD was diagnosed in 152 cases based on ultrasound and steatometry findings. Fecal zonulin levels were measured by ELISA. Small intestinal bacterial overgrowth (SIBO) was diagnosed using hydrogen breath testing. Correlations between zonulin, inflammatory markers (high-sensitivity C-reactive protein, hsCRP), lipid profiles, and SIBO prevalence were analyzed.

Results

SIBO was detected in 45% of patients with dyslipidemia and 53.2% of patients with MASLD. Fecal zonulin levels in patients with MASLD (115±2.76 ng/g) significantly exceeded the normal upper limit (≤107 ng/g) and were higher compared to patients without steatosis. Zonulin levels positively correlated with hsCRP (r=0.65, p<0.05) and triglycerides (r=0.58, p<0.05). A strong negative correlation was observed between SIBO presence and HDL-C levels (r=–0.78, p<0.05) in patients with dyslipidemia.

Conclusion

Elevated zonulin levels and increased intestinal permeability are closely associated with systemic inflammation and lipid metabolism disturbances in MASLD. Zonulin and SIBO may represent novel therapeutic targets for the prevention and treatment of MASLD and metabolic disorders.