A groundbreaking meta-analysis recently published in the reputable journal eGastroenterology has unveiled a striking paradox in the management of Helicobacter pylori (H. pylori) infections. While eradication of this widely prevalent gastric pathogen remains fundamental in preventing serious gastrointestinal diseases such as peptic ulcers and gastric cancer, the comprehensive study now suggests that such treatment may surprisingly increase the risk of reflux oesophagitis (RE). This revelation challenges conventional therapeutic strategies and urges clinicians to reconsider the broader implications of H. pylori eradication beyond its immediate benefits.
The international team of researchers, led by Professor Mingxin Zhang and collaborators from Xi’an Medical University and its affiliated hospital, undertook a systematic review and meta-analysis encompassing 30 rigorous scientific studies. These included 16 randomized controlled trials (RCTs) and 14 prospective cohort studies—all carefully selected through exhaustive searches across major databases including PubMed, Embase, Web of Science, and the Cochrane Library, covering literature up to December 2024. This comprehensive approach allowed a robust synthesis of data evaluating the incidence or recurrence of reflux oesophagitis following H. pylori eradication therapy.
In their meticulous data analysis using Review Manager 5.4 software, the researchers identified a 39% increased risk of developing or experiencing recurrence of RE in patients undergoing H. pylori eradication therapy compared to placebo groups, as demonstrated by pooled data from the RCTs. This result, importantly, exhibited low heterogeneity (I²=28%), underscoring its statistical robustness and generalizability. Contrastingly, the cohort studies’ findings were less definitive, with high heterogeneity (I²=78%) and without achieving statistical significance, thereby suggesting intricate confounding influences in real-world observational data.
Delving deeper into age stratifications, the meta-analysis revealed no statistically significant increase in RE risk across different age categories—including younger adults (≤40 years), middle-aged individuals (40–60 years), and seniors (≥60 years). Nonetheless, a non-significant yet consistent trend of elevated relative risk in middle-aged groups was notable across study designs, hinting at potential age-related biological and environmental interactions modulating the post-eradication trajectory of the gastroesophageal mucosa.
Crucially, the presence of pre-existing gastrointestinal illnesses appeared to modulate risk profiles. In particular, patients diagnosed with peptic ulcer disease (PUD) exhibited a markedly higher RE risk post-eradication in randomized trials, a finding not mirrored in cohort studies. Conversely, no significant alterations in RE occurrence were observed among those with gastroesophageal reflux disease (GERD) or dyspepsia, although some prospective cohorts indicated an increase in dyspeptic patients. These nuanced differences underscore the complex pathophysiological interplay between H. pylori infection, mucosal integrity, and acid-related disorders.
Geographic analyses further illuminated intriguing variations in RE susceptibility following eradication therapy. While RCT data suggested elevated but statistically non-significant risks across Asia, the Americas, and Europe, cohort studies sharply delineated a significant risk elevation particularly within Asian populations, an observation absent in European cohorts. These findings emphasize the potential influence of region-specific factors such as genetic predispositions, dietary habits, microbiome compositions, and environmental exposures on disease progression and therapeutic response.
One of the more illuminating aspects of the study pertained to the temporal dynamics of RE risk. Longer follow-up durations exceeding one year consistently correlated with a significant increase in RE incidence, reinforcing a time-dependent deterioration of esophageal mucosal defenses or compensatory physiological changes after the clearance of H. pylori. This temporal association suggests that short-term assessments may underestimate the long-term gastroesophageal risks associated with eradication therapies.
From a mechanistic standpoint, this research invites a re-examination of H. pylori’s dualistic role within the upper gastrointestinal tract. Traditionally vilified as a pathogenic bacterium necessitating elimination, H. pylori may also exert protective effects against acid reflux by modulating gastric acid secretion and influencing gastric physiology. Its eradication likely disrupts this delicate balance, culminating in increased acid exposure, esophageal mucosal inflammation, and thus heightened RE risk, particularly in susceptible individuals.
The clinical ramifications of these findings are profound and multi-faceted. While H. pylori eradication indisputably remains vital for gastric cancer and ulcer prevention, a blanket ‘treat-all’ approach must now be tempered by an appreciation of potential downstream complications such as reflux oesophagitis. Physicians are urged to adopt a more personalized therapeutic strategy—carefully evaluating individual patient profiles, including age, baseline gastrointestinal health, and regional epidemiology—before initiating eradication protocols.
Moreover, diligent post-therapy monitoring emerges as a crucial component of patient management. Individuals undergoing treatment should be closely observed for reflux symptoms, facilitating early intervention and mitigating the risk of chronic esophagitis or its sequelae. This may encompass lifestyle modifications, pharmacologic acid suppression, or tailored follow-up endoscopies to preserve esophageal health.
Nevertheless, the authors candidly acknowledge the study’s limitations. The significant heterogeneity in cohort studies points to the complexities of observational research, including diverse patient populations, varied study designs, and potential confounders. Language restrictions to English and Chinese publications, as well as omission of unpublished data, may introduce selection bias. Furthermore, inconsistent reporting across studies hindered assessments of RE severity and precise temporal onset post-eradication. Lastly, reliance on infection status at final follow-up instead of initial eradication regimens may have induced some misclassification bias.
Despite these constraints, the meta-analysis’s rigor and the convergence of evidence from well-designed RCTs amplify the validity of its conclusions. This integrative work charts new territory in gastroenterological research, underscoring the multifaceted consequences of microbial manipulation within human hosts—especially in the tightly regulated milieu of the gastrointestinal tract.
In summation, this pivotal meta-analysis compellingly elucidates that while H. pylori eradication therapy remains a cornerstone of gastrointestinal disease prevention, it paradoxically may increase the risk of reflux oesophagitis, particularly with extended follow-up periods. These risks are nuanced, influenced by regional, demographic, and clinical variables, necessitating a more individualized and judicious approach to H. pylori treatment algorithms. Ultimately, this study highlights an urgent need for both enhanced awareness and further research into balancing microbial eradication benefits against potential gastrointestinal sequelae.
By decoding the intricate interplay between microbial infection, eradication strategies, and esophageal pathology, the findings pave the way for improved clinical guidelines and patient outcomes. As the global medical community continues to grapple with evolving understandings of the human microbiome’s role in health and disease, such comprehensive analyses serve as vital touchstones in shaping nuanced, patient-centric care paradigms.
Subject of Research: Association between Helicobacter pylori eradication and risk of reflux oesophagitis occurrence or recurrence.
Article Title: Association between infection of Helicobacter pylori and the risk of reflux oesophagitis occurrence or recurrence: a systematic review and meta-analysis.
News Publication Date: 2025.
Web References:
- DOI link: http://dx.doi.org/10.1136/egastro-2024-100121
- eGastroenterology Journal: egastroenterology.bmj.com
References: Li A, Zhang Y, Chen K, et al. Association between infection of Helicobacter pylori and the risk of reflux oesophagitis occurrence or recurrence: a systematic review and meta-analysis. eGastroenterology 2025;3:e100121.
Image Credits: Anna Li, Yanan Zhang, Kunping Chen, et al.
Keywords: Helicobacter pylori, reflux oesophagitis, eradication therapy, meta-analysis, randomized controlled trials, prospective cohort studies, gastroesophageal reflux disease, peptic ulcer disease, gastric cancer prevention, gastrointestinal microbiota, acid reflux, esophageal mucosa, regional variations.
