Effectiveness of Helicobacter pylori eradication in the treatment of early-stage gastric mucosa-associated lymphoid tissue lymphoma: An up-to-date meta-analysis

Abstract

Background: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML) is usually a low-grade B-cell neoplasia strongly associated with Helicobacter pylori (H. pylori)-induced chronic gastritis. Clinical practice guidelines currently recommend H. pylori eradication as the preferred initial treatment for early-stage GML. To determine the practical effect of bacterial eradication as the sole initial therapy for early-stage GML, an updated analysis and review of available evidence is imperative.

Aim: To perform a meta-analysis to assess the rate of complete remission (CR) of H. pylori-positive early-stage GML following bacterial eradication.

Methods: We performed independent, computer-assisted literature searches using the PubMed/MEDLINE, Embase, and Cochrane Central databases through September 2022. Prospective and retrospective observational studies evaluating the CR of early-stage GML following bacterial eradication in H. pylori-positive patients. The risk of bias was assessed using Joanna Briggs Institute (JBI) Critical Appraisal Tools. The pooled estimate of the complete histopathological remission rate and respective confidence intervals (95%CI) were calculated following the random-effects model. Heterogeneity and inconsistency were assessed using Cochran's Q test and I² statistic, and heterogeneity was defined as P < 0.01 and I² > 50%, respectively. Subgroup and meta-regression analyses were conducted to explore potential sources of heterogeneity.

Results: The titles and abstracts of 1576 studies were screened; 96 articles were retrieved and selected for full-text reading. Finally, 61 studies were included in the proportional meta-analysis (P-MA). Forty-six were prospective and fifteen were retrospective uncontrolled, single-arm, observational studies. The overall risk of bias was low to moderate in all but a single report, with an average critical appraisal score across all studies of 79.02%. A total of 2936 H. pylori-positive early-stage GML patients, in whom H. pylori was successfully eradicated, were included in the analysis. The pooled CR of H. pylori-positive early-stage GML after bacterial eradication was 75.18% (95%CI: 70.45%-79.91%). P-MA indicated the substantial heterogeneity in CR reported across studies (I ² = 92%; P < 0.01). Meta-regression analysis identified statistically significant effect modifiers, including the proportion of patients with t(11;18)(q21;q21)-positive GML and the risk of bias in each study.

Conclusion: Comprehensive synthesis of available evidence suggests that H. pylori eradication is effective as the sole initial therapy for early-stage GML. Although the substantial heterogeneity observed across studies limits the interpretation of the pooled overall CR, the present study is a relevant to informing clinical practice.

Keywords: B-cell; Eradication therapy; Gastric mucosa-associated lymphoid tissue lymphoma; Helicobacter pylori; Lymphoma; Marginal zone; Stomach lymphoma; Therapeutics.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 flow diagram. The flow chart describes the flow of information through the different stages of the systematic review and maps the number of records identified, included, and excluded, and the reasons for study exclusion. H. pylori: Helicobacter pylori.

Figure 2

Risk of bias assessment by the Joanna Briggs Institute Critical Appraisal Tool. The critical appraisal checklist for case series consists of 10 questions: Q1: Were there clear criteria for inclusion in the case series? Q2: Was the condition measured in a standard, reliable way for all participants included in the case series? Q3: Were valid methods used for identification of the condition for all participants included in the case series? Q4: Did the case series have consecutive inclusion of participants? Q5: Did the case series have complete inclusion of participants? Q6: Was there clear reporting of the demographics of the participants in the study? Q7: Was there clear reporting of clinical information of the participants? Q8: Were the outcomes or follow-up results of cases clearly reported? Q9: Was there clear reporting of the presenting site(s)/clinic(s) demographic information? Q10: Was statistical analysis appropriate? The percentage of risk of bias was calculated by the number of “yes” answers selected in the checklist. Questions with “not applicable” answers were not considered in the calculation. The risk of bias was classified using the following categories: High (scores up to 49.0%), moderate (scores between 50.0% and 70.0%), and low (scores above 70.0%). A: Overall risk of bias; B: Risk of bias summary: Discriminated assessments for each question across all studies. N/A: Not applicable.

Figure 3

Overall complete remission rate of Helicobacter pylori-positive early-stage gastric mucosa-associated lymphoid tissue lymphoma. A: After eradication therapy; B: After eradication therapy by study design. CI: Confidence interval.