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, 9 (9), e026002

Helicobacter pylori Eradication Treatment for Gastric Carcinoma Prevention in Asymptomatic or Dyspeptic Adults: Systematic Review and Bayesian Meta-Analysis of Randomised Controlled Trials

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Helicobacter pylori Eradication Treatment for Gastric Carcinoma Prevention in Asymptomatic or Dyspeptic Adults: Systematic Review and Bayesian Meta-Analysis of Randomised Controlled Trials

Teruhiko Terasawa et al. BMJ Open.

Abstract

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.

Keywords: Helicobacter pylori; cancer prevention; eradication treatment; gastric carcinoma.

Conflict of interest statement

Competing interests: All authors declare no conflicts of interest associated with this publication. For complete transparency, TY reports taking grants and personal fees from Chugai Pharmaceutical Co., grants and personal fees from Taiho Pharmaceutical, grants and personal fees from Yakult, personal fees from Lilly, grants from Novartis, personal fees from Ono, personal fees from Takeda, personal fees from Nippon Kayaku Co., personal fees from Covidien, personal fees from Johnson and Johnson, personal fees from Olympus, personal fees from NPO Epidemiological and Clinical Research Information Network, personal fees from NPO KSATTS, and personal fees from NPO Cancer Net Japan, outside the submitted work.

Figures

Figure 1
Figure 1
Effect of eradication therapy on gastric carcinoma incidence, gastric carcinoma-specific mortality, non-gastric carcinoma mortality, and all-cause mortality in asymptomatic or dyspeptic Helicobacter pylori-infected adults. Diamonds represent the summary HRs centred on a combined estimate and extending to 95% credible intervals (CrIs), with estimated 95% prediction intervals (PrIs) depicted as horizontal lines. Black squares and horizontal lines indicate crude ‘observed’ HRs and 95% CIs. Grey squares and horizontal lines indicate ‘adjusted’ HRs and 95% CrIs based on the posterior distribution for individual studies. The size of the square is proportional to the inverse of the variance of the logarithm-transformed HR of each study. Studies are ordered by publication year. The colours of the CIs and CrIs for non-gastric carcinoma mortality and all-cause mortality for the study by Ma et al are inverted. PrI, prediction interval.

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