Meta-analysis used to identify factors associated with the effectiveness of proton pump inhibitors against non-erosive reflux disease


Dr Toru Hiyama, Health Service Center, Hiroshima University, 1-7-1 Kagamiyama, Higashihiroshima 739-8521, Japan. Email:


Background:  A lack of published data remains on factors associated with the treatment response to proton pump inhibitors (PPI) in patients with non-erosive reflux disease (NERD).

Methods:  Studies on effectiveness of PPI in patients with NERD were identified using the MEDLINE database and manual searches of the available literature. Twenty publications that comprised a total of 22 study arms were eligible, and meta-analyses of these 22 study arms were carried out.

Results:  Overall improvement rate in patients with PPI was 68%. Univariate meta-regression analysis was used to explore the source of heterogeneity, P-value for males was 0.192, and in the presence of Helicobacter pylori (H. pylori) infection was 0.186, indicating that these factors are associated with treatment effectiveness. Thus, as the frequency of male and H. pylori-infected patients increased, the effectiveness of PPI against NERD improved. By multivariate meta-regression analysis, the P-value for male and H. pylori infection decreased further (P = 0.002 and P = 0.003, respectively), indicating little interaction between male sex and H. pylori infection.

Conclusion:  These results suggest that H. pylori infection and patient sex may be associated with the effectiveness of PPI against patients with NERD. The reasons are still unclear, and further examinations are needed to clarify them.