Review for 10.1186/s12876-025-04034-3 (2025)

Title: Gastric cancer risk after Helicobacter pylori eradication in gastritis and peptic ulcer: a
retrospective cohort study in Japan
Version: 1 Date: 26 Feb 2025
Reviewer's report:
This manuscript, titled "Gastric cancer risk after Helicobacter pylori eradication in gastritis
and peptic ulcer: a retrospective cohort study in Japan," presents a retrospective cohort study
examining the impact of H. pylori eradication therapy on the risk of gastric cancer in patients
with different gastric conditions (gastritis, gastric ulcer, duodenal ulcer, and gastric and duodenal
ulcer).
The study utilized a large cohort, with over 17 million beneficiaries in Japan, and an analysis
spanning a decade. This increases the power of the study and provides robust data for the
analysis.
The use of the JMDC Claims Database, which includes detailed health insurance claims data, is
a valuable resource. It allows for a large-scale retrospective cohort analysis while minimizing
selection bias through the use of propensity score matching.
The manuscript’s objective is well-defined to assess the differences in gastric cancer risk
among patients with different gastric conditions following H. pylori eradication therapy. This
is important as it helps to understand the long-term outcomes of H. pylori eradication therapy,
particularly in Japan, where H. pylori eradication therapy has been part of the national health
insurance program since 2013.
The study uses robust statistical methods, including Cox proportional hazards regression and
propensity score matching, to minimize bias and confounding. The use of multiple sensitivity
analyses adds rigor to the findings.
Since the study uses claims data, it reflects a real-world clinical setting, which enhances the
external validity of the results. This is particularly important for understanding the outcomes in
a population-based sample rather than a controlled trial.
Limitations:
1. Although propensity score matching is used, the study is retrospective, and there may still
be residual confounding. For example, some factors such as the presence or severity of gastric
atrophy, history of gastric cancer, adherence to H. pylori eradication therapy and outcome of
eradication therapy could not be fully accounted for.
2. Misclassification Risk: The study relies on ICD-10 codes for diagnosis, and misclassification
of conditions like gastric atrophy or H. pylori infection could impact the results. The database
does not contain detailed clinical data, such as endoscopic findings or biopsy results, which
might lead to inaccuracies in categorizing patients.
3. Short Follow-Up Period: The follow-up period of the study is relatively short, with a median of
about 3.8 years. Gastric cancer may take longer to develop post-eradication, and a longer follow-
up period would have provided a better understanding of the long-term risks. A recent 24-year
long-term follow-up study demonstrated a declining trend in gastric cancer incidence beyond
five years after H. pylori eradication. The standardized incidence ratio (SIR) for all cohort
participants was initially higher than that of the background population (SIR 2.27 [95% CI 2.10–
2.44] within 1–5 years post-eradication), but progressively decreased over time, approaching
the level of the background population after 11–24 years of follow-up (SIR 1.11 [95% CI
0.98–1.27])( Gastroenterology 2025 Feb 7:S0016-5085(25)00356-7). These findings suggest
that to fully elucidate the impact of H. pylori eradication on gastric cancer risk across different
disease groups, longer follow-up studies are warranted. Additionally, the study reported a higher
incidence of gastric cancer in the gastric ulcer group compared to the gastritis group. However,
it remains unclear whether this discrepancy arises from differences in clinical diagnosis, the
presence of underlying atrophic gastritis, or variations in the severity of gastric atrophy, making
the clinical implications of these findings uncertain.
It is difficult to determine from the data in this study whether the difference in gastric cancer
incidence after H. pylori eradication is attributable to variations in disease status or to the
presence and severity of underlying atrophic gastritis. However, drawing a definitive conclusion
based on this uncertainty may be considered an overstatement.
4. Although the study attempts to control for selection bias using propensity scores, there is still a
potential for bias since it is based on a database of health insurance claims. The study population
may not be fully representative of the general population, especially those aged 65 and older,
since the JMDC database primarily includes employees and their families.
Conclusion:
The manuscript provides valuable insight into the long-term risks of gastric cancer following
H. pylori eradication therapy, with a focus on patients with gastritis, and ulcers. The findings
suggest that gastric cancer risk remains elevated in patients with gastritis, GU and DU,
highlighting the importance of the presence of gastric atrophy, but it was not evaluated in
this study. The study offers important information for clinicians regarding the long-term
management of patients after H. pylori eradication therapy, emphasizing the need for regular
endoscopic surveillance in high-risk groups
The study’s strengths lie in its large sample size, real-world data, and robust statistical analysis.
However, limitations such as the retrospective design, short follow-up period, and potential for
confounding should be acknowledged.