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Dramatic shift in the epidemiology of peptic ulcer in Japan: the impact of Helicobacter pylori eradication therapy

ABSTRACT: Helicobacter pylori eradication therapy was included with insurance coverage from 1999 onwards in Japan, with the incidence of peptic ulcer expected to decrease as a consequence. This study investigated the temporal dynamics of peptic ulcer in Japan and identified underlying contributory factors using mathematical models. We investigated the seroprevalence of H. pylori and analysed a snapshot of peptic ulcer cases. Ten statistical models that incorporated important events – H. pylori infection, the cohort effect, eradication therapy and the natural trend for reduction – were fitted to the case data. The hazard of infection with H. pylori was extracted from published estimates. Models were compared using the Akaike information criterion (AIC), and factor contributions were quantified using the coefficient of determination. The best-fit model indicated that 88.1% of the observed snapshot of cases (AIC = 289.2) included the effects of (i) H. pylori infection, (ii) the cohort effect and (iii) eradication therapy, as explanatory variables, the contributions of which were 80.8%, 4.0% and 3.2%, respectively. Among inpatients, a simpler model with (i) H. pylori infection only was favoured (AIC = 107.7). The time-dependent epidemiological dynamics of peptic ulcers were captured and H. pylori infection and eradication therapy explained ⩾84% of the dramatic decline in peptic ulcer occurrence.

SUBMITTER: Lee K

PROVIDER: S-EPMC8753483 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMost peptic ulcer cases are associated with Helicobacter pylori (H. pylori) infection or the use of nonsteroidal anti-inflammatory drugs (NSAIDs). H. pylori eradication therapy is recommended for the treatment of H. pylori-positive peptic ulcers. We aimed to assess and validate the cumulative economic and health effects of H. pylori eradication strategy for the treatment of peptic ulcers compared with PPI therapy strategy.Materials and methodsWe developed a cohort state-transition model for H. pylori eradication strategy and PPI therapy strategy over a lifetime horizon from a healthcare payer perspective. We targeted two hypothetical cohorts of H. pylori-positive patients with gastric and duodenal ulcers aged 20, 30, 40, 50, 60, 70, and 80. The main outcomes were costs, quality-adjusted life-years (QALYs), life expectancy life-years (LYs), incremental cost-effectiveness ratios, ulcer recurrence cases, and ulcer-associated deaths. One-way and probabilistic sensitivity analyses were conducted to assess the impact of uncertainty.ResultsIn the base-case analysis, H. pylori eradication strategy was less costly with greater benefits than PPI therapy strategy in all age groups. Cost-effectiveness was not sensitive to any variables in all age groups. Sensitivity analyses showed strong robustness of the results. From 2000 to 2020, H. pylori eradication strategy saved US$14.07 billion over a lifetime, increased 8.65 million QALYs and 1.23 million LYs over a lifetime, and prevented 551,298 ulcer recurrence cases and 59,465 ulcer-associated deaths, compared with PPI therapy strategy.ConclusionsH. pylori eradication strategy not only has contributed significantly to preventing ulcer recurrence and reducing ulcer-associated deaths but also has resulted in great cost savings. All over the world, H. pylori eradication strategy is likely to have yielded a comparable magnitude of economic and health benefits, depending on the epidemiology of H. pylori-related peptic ulcers and the healthcare environment in each country.

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.

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Dramatic shift in the epidemiology of peptic ulcer in Japan: the impact of Helicobacter pylori eradication therapy

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