The relationship between inflammatory bowel disease and Helicobacter pylori across East Asian, European and Mediterranean countries: a meta-analysis

Abstract

Background: The current literature suggests a protective benefit of Helicobacter pylori (H. pylori) infection against inflammatory bowel disease (IBD). Here we assessed whether this effect varied by IBD subtype-Crohn's disease (CD) or ulcerative colitis (UC)-and geographic region: East Asia, Europe (non-Mediterranean) or Mediterranean region.

Methods: A database search was performed up to July 2019 inclusive for all studies that compared H. pylori infection in IBD patients vs. non-IBD controls. The relative risk (RR) was used to quantify the association between IBD and H. pylori, and the effects were combined across studies using a mixed-effects meta-regression model, which included IBD subtype and geographic region as categorical moderator variables.

Results: Our meta-regression model exhibited moderate heterogeneity (I²=48.74%). Pooled RR depended on both region (P=0.02) and subtype (P<0.001). Pooled RRs were <1 for all subtype and region combinations, indicative of a protective effect of H. pylori against IBD. The pooled RR was 28% (9%, 50%; P=0.001) greater for UC vs. CD and 43% (4%, 96%; P=0.02) greater for Mediterranean countries vs. East Asia. The pooled RR was 18% (-13%, 60%; P=0.48) greater for Europe vs. East Asia and 21% (-13%, 68%; P=0.42) greater for Mediterranean vs. Europe, though these differences were not statistically significant.

Conclusions: The protective effect of H. pylori on IBD varied by both subtype (more protection against CD vs. UC) and region (East Asia more protected than Mediterranean regions). Variation due to these effects could provide insight into IBD etiology.

Keywords: East Asia; Europe; Helicobacter pylori; Mediterranean; inflammatory bowel disease.

Figure 1

Study flow diagram showing identification, screening and eligibility stages which resulted in 32 studies being included in our meta-analysis N; number

Figure 2

Relative risks (RR) and 95% confidence intervals for each primary study by region and subtype (CD = Crohn’s disease; UC = ulcerative colitis. The pooled summary effects are shown at the base of the plot aligned with ‘All’. Vertical dashed lines are shown at RR=1 to indicate the null effect (confidence intervals that do not include 1 are statistically significant at P<0.05)

Figure 3

Ratios of relative risks (RRR) and 95% confidence intervals for pre-specified contrasts of moderator variables (region and subtype) included in our meta-regression model. RRR represent average effects, pooled over levels of the other moderator in the model. Confidence intervals are adjusted for simultaneous inference using the single-step method. The vertical dashed line at RRR=1 indicates the null effect (confidence intervals that do not include 1 are statistically significant at P<0.05)

Figure 4

Standard funnel plot for all studies included in our meta-regression model. The cluster of studies on the lower left side might be suggestive of small study bias

Figure 5

Contour-enhanced funnel plot for all studies included in our meta-regression model. The plot is approximately symmetrical and is not indicative of publication bias. All of the smaller studies (larger standard error towards base of plot) lie within 0.10