Helicobacter pylori eradication therapy linked to increased risk of reflux oesophagitis

The management of Helicobacter pylori (H. pylori), a globally prevalent gastric pathogen, has long been centered on its eradication to prevent peptic ulcers, gastric malignancies, and related gastrointestinal complications. However, a newly published meta-analysis in eGastroenterology raises a crucial clinical dilemma: Could the treatment itself, intended to heal, paradoxically increase the risk of reflux oesophagitis (RE)? Led by Prof. Mingxin Zhang and colleagues from Xi'an Medical University and The First Affiliated Hospital of Xi'an Medical University, this comprehensive systematic review and meta-analysis synthesizes findings from 30 studies, offering a clearer picture of the association between H. pylori eradication and RE development or recurrence.

The authors conducted a systematic search across PubMed, Embase, Web of Science, and the Cochrane Library up to December 2024. Eligible studies were randomized controlled trials (RCTs) or prospective cohort studies evaluating the occurrence or recurrence of RE following H. pylori eradication. In total, 16 RCTs and 14 prospective cohort studies were included. The meta-analysis was conducted using Review Manager 5.4, and subgroup analyses explored the role of age, region, underlying diseases, and duration of follow-up. The study was registered with PROSPERO (CRD42024529321) and adhered to PRISMA guidelines.

Key findings

(1) Overall increased risk after eradication

In the RCTs, patients who underwent H. pylori eradication had a 39% higher risk of developing or experiencing recurrence of RE compared to those in placebo groups. This result was statistically significant and showed low heterogeneity (I²=28%), strengthening its reliability. Conversely, the pooled data from prospective cohort studies did not reach statistical significance, and heterogeneity was high (I²=78%), indicating potential confounding factors.

(2) Age-based subgroup analysis

Subgroup analysis by age revealed no statistically significant increase in RE risk across young (≤40 years), middle-aged (40–60 years), or elderly (≥60 years) groups. However, most data came from middle-aged patients, where the RR remained elevated but non-significant in both RCTs and cohort studies, suggesting a potential trend.

(3) Impact of underlying disease

Among patients with peptic ulcer disease (PUD), eradication was significantly associated with a higher RE risk in RCTs, but not in cohort studies. In contrast, no significant difference was found among patients with GERD, RE, or dyspepsia across both study designs, although dyspepsia patients in cohort studies showed a notable increase.

(4) Regional differences

Geographic variations in risk were modest. RCTs showed elevated but not statistically significant risk increases in Asia, the Americas, and Europe. Among cohort studies, Asian populations demonstrated a significant risk elevation, whereas European populations did not. These findings point to potential environmental, genetic, or dietary modifiers.

(5) Follow-up duration matters

Time emerged as a critical factor. In RCTs with >1 year follow-up, the risk of RE was significantly increased, suggesting a time-dependent effect of eradication. Similarly, long-term follow-up cohort studies showed higher RE incidence, whereas short-term data did not show a difference.

Clinical implications

The findings call for a nuanced approach to H. pylori management. While eradication remains essential in preventing ulcers and gastric malignancies, clinicians should weigh the potential trade-offs, especially for patients without clear indications for therapy. In practice, individual factors such as age, existing gastrointestinal conditions, and regional background should inform clinical decisions. Moreover, monitoring patients post-eradication for reflux symptoms may be prudent, particularly in those with predisposing factors or prior RE episodes.

The authors acknowledge several limitations: (1) High heterogeneity in cohort studies due to variable designs and populations; (2) Exclusion of non-English/Chinese studies and unpublished data, introducing potential selection bias; (3) Inability to assess the severity and timing of RE symptoms post-eradication due to lack of consistent reporting; (4) The reliance on infection status at final follow-up, not the initial treatment regimen, may introduce misclassification bias. Despite these issues, the large dataset and consistent findings from RCTs enhance confidence in the results.

In conclusion, this landmark meta-analysis underscores that H. pylori eradication therapy-though beneficial in many respects-may elevate the risk of reflux oesophagitis, particularly with long-term follow-up. The effect is modified by region, age, and baseline disease but remains clinically meaningful. Physicians are urged to personalize H. pylori treatment strategies and consider patient-specific risks for RE before initiating eradication therapy.