Dataset Information

Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials.

ABSTRACT:

Objectives

To determine whether searching for Helicobacter pylori and treating with eradication therapy leads to a reduction in incidence of gastric cancer among healthy asymptomatic infected individuals.

Design

Systematic review and meta-analysis of randomised controlled trials.

Data sources

Medline, Embase, and the Cochrane central register of controlled trials were searched through to December 2013. Conference proceedings between 2001 and 2013 were hand searched. A recursive search was performed with bibliographies of relevant studies. There were no language restrictions.

Eligibility criteria for selecting studies

Randomised controlled trials examining the effect of at least seven days of eradication therapy on subsequent occurrence of gastric cancer in adults who tested positive for Helicobacter pylori but otherwise healthy and asymptomatic were eligible. The control arm had to receive placebo or no treatment. Subjects had to be followed for ≥ 2 years.

Main outcome measures

Primary outcome, defined a priori, was the effect of eradication therapy on the subsequent occurrence of gastric cancer expressed as a relative risk of gastric cancer with 95% confidence intervals.

Results

The search strategy identified 1560 citations, of which six individual randomised controlled trials were eligible. Fifty one (1.6%) gastric cancers occurred among 3294 individuals who received eradication therapy versus 76 (2.4%) in 3203 control subjects (relative risk 0.66, 95% confidence interval 0.46 to 0.95), with no heterogeneity between studies (I(2)=0%, P=0.60). If the benefit of eradication therapy was assumed to persist lifelong the number needed to treat was as low as 15 for Chinese men and as high as 245 for US women.

Conclusions

These data provide limited, moderate quality evidence that searching for and eradicating H pylori reduces the incidence of gastric cancer in healthy asymptomatic infected Asian individuals, but these data cannot necessarily be extrapolated to other populations.

SUBMITTER: Ford AC

PROVIDER: S-EPMC4027797 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVES:Recent meta-analyses of eradication therapy in Helicobacter pylori-infected adults reported significant reductions in gastric carcinoma risk. However, concerns about supporting unfocused screening and eradication programme in healthy, asymptomatic populations have arisen. We performed a systematic review and Bayesian meta-analysis to provide an accurate interpretation of randomised evidence on the preventive effectiveness of eradication therapy on gastric carcinoma risk. METHODS:We searched databases including PubMed, Cochrane Central and Embase for reference and citation tracking without language restrictions, from inception through 31 July 2018. Paired investigators independently selected randomised controlled trials (RCTs) comparing eradication therapy with placebo or no treatment for asymptomatic or dyspeptic H. pylori-infected adults with no previous gastric carcinoma. The main outcome was gastric carcinoma incidence; secondary outcomes included gastric carcinoma-specific, non-gastric carcinoma and all-cause mortality. RESULTS:A total of 5 population-based and 2 outpatient care-based RCTs involving 7303 adults were eligible. Eradication algorithms were heterogeneous, and unsuccessful eradication and reinfection were frequently observed. A Bayesian meta-analysis with competing risk outcomes found low-certainty evidence that eradication therapy might be more likely than control to reduce gastric carcinoma risk (HR=0.65; 95% credible interval (CrI) 0.41 to 1.0; I2 =11%). The CrIs included the null effects across the subgroup and sensitivity analyses, apart from those based on particular models that excluded two RCTs that enrolled subjects with specific histological findings only (HR=0.55; CrI 0.30 to 0.89; I2 =14%). The uncertainty of the average 41% risk reduction in gastric carcinoma-specific mortality included a clinically important mortality risk increase (HR=0.59 favouring eradication therapy; CrI 0.25 to 1.20; I2 =13%; low certainty). CONCLUSIONS:There is insufficient evidence to support or refute the effectiveness of eradication therapy in preventing gastric carcinoma in H. pylori-infected, high-risk populations. Rigorously conducted large RCTs of healthy infected adults only would provide evidence of the true efficacy of successful eradication. PROSPERO registration number: CRD42014009245.

Project description:BackgroundHelicobacter pylori (Hp) eradication has been used for many years. Yet, the impact of this eradication on the normal gastric microflora is not well understood. In this study, we explored the effect of eradication on the stomach microbial community and its recovery after successful Hp eradication.MethodsAmong the 89 included patients, 23, 17, 40, and 9 were included in the Hp-negative, Hp-positive, successful eradication, and failed eradication groups, respectively. Four subgroups were further determined according to disease status (Hp-negative chronic gastritis [N-CG], Hp-negative atrophic gastritis [N-AG], successful-eradication chronic gastritis [SE-CG], and atrophic gastritis with successful eradication [SE-AG]). During the endoscopic examination, one piece of gastric mucosa tissue was obtained from the lesser curvature side of the gastric antrum and gastric corpus, respectively. In addition, 16S rDNA gene sequencing was used to analyze the gastric mucosal microbiome.ResultsIn the Hp-negative group, the gastric microbiota was dominated by five phyla: Firmicutes, Proteobacteria, Actinobacteria, Bacteroidetes, and Fusobacteria. After successfully eradicating Hp, the bacterial flora in the stomach recovered to a considerable extent. In the failed eradication group, the flora was similar to the flora in Hp-positive subjects based on the alpha and beta diversities. Among the groups, Curvibacter and Acinetobacter were enriched in the presence of Hp (i.e., failed eradication and Hp-positive groups), suggesting that these two genera could be used as biomarkers in the symbiotic flora in the presence of Hp. SE-CG was characterized by an increase in Firmicutes taxa and a decrease in Proteobacteria taxa compared with N-CG. SE-AG was characterized by a decrease in Firmicutes relative to N-AG. Finally, no differences were found in the pairwise comparisons of nitrate and nitrite reductase functions of the microflora among the four subgroups.ConclusionsAfter Hp infection, the diversity and relative abundance of gastric microflora were significantly decreased. Yet, gastric microbiota could be partially restored to the Hp-negative status after eradication. Still, this effect was incomplete and might contribute to the long-term risks.