H. pylori Infection and Marsh Classification in Celiac Disease: Insights from a Mixed-Methods Approach

Aim: Previous studies have reported conflicting associations between Helicobacter pylori infection and celiac disease (CD). Some suggest a protective effect, whereas others propose a pathogenic role. These inconsistencies may be due to overlapping histological features such as intraepithelial lymphocytosis and duodenitis. This study aimed to evaluate the clinical and histopathological consequences of H. pylori infection in biopsy-proven CD cases. Materials and Methods: Between 2017 and 2025, a dual-center, convergent parallel mixed-methods study was conducted with 377 participants (226 CD patients, 151 controls). Quantitative analyses assessed clinical symptoms, histopathological features, and Marsh classification, with H. pylori status evaluated using chi-square tests, logistic regression, and odds ratios. In addition, purposively selected CD patients underwent semi-structured interviews exploring abdominal pain, weakness, dietary experiences, and perceptions of H. pylori diagnosis. Results: The prevalence and semi-quantitative severity of H. pylori colonization were similar between CD and control groups (44.6% vs. 44.2%, p = 0.947), with no significant correlation to Marsh grades. Histopathology revealed antral gastritis, pangastritis, duodenitis, and duodenal ulcers more frequently in controls, while villous atrophy with crypt hyperplasia was higher in CD patients (43.2% vs. 1.3%, p < 0.001). Clinically, weakness was more common in CD patients (24.8% vs. 10.6%, p < 0.001), whereas abdominal pain was more frequent in controls (77.5% vs. 44.7%, p < 0.001). Qualitative findings highlighted fatigue as an “invisible disability” and reflected uncertainty about symptom improvement following H. pylori eradication. Conclusion: H. pylori colonization was not associated with histopathological severity in CD, supporting evidence that it has neither a protective nor pathogenic role. While H. pylori–related lesions were more frequent in dyspeptic controls, CD-specific mucosal injury remained distinct. Fatigue emerged as a key symptom in qualitative accounts, underscoring the need for patient-centered management. Future prospective, strain-level, and multi-center studies are warranted to clarify potential context-dependent interactions.