Hepatitis B Virus, Helicobacter pylori and High-Risk Events of Gastric Cancer Development: An Observational Study...

Background: Hepatitis B virus (HBV) is an infection proven to increase the risk of gastric cancer, especially among hepatitis B virus surface antigen (HBsAg) seropositive patients. However, the route through which HBV injures gastric mucosa and its mechanism of gastric carcinogenesis are still under investigation. Aims: The present study aimed to observe and evaluate associations between HBV infection with Helicobacter pylori, atrophic gastritis, and some other high-risk events for gastric cancer development. Methods: A retrospective cross-sectional study recruited participants undergoing a health check-up between 2018 and 2020 in the West China Hospital of Sichuan University. Participants were stratified into three statuses, including Group A (non-HBV infection), Group B (resolved HBV infection), and Group C (chronic HBsAg carriers or active HBV infection). Additionally, Groups A and B were categorized as HBsAg-seronegative, whereas Group C was defined as HBsAg-seropositive. High-risk events of gastric cancer included a history of gastric ulcer, Helicobacter pylori infection, serological atrophic gastritis (serum pepsinogens), hypergastrinemia (serum gastrin-17), and endoscopic findings of atrophic gastritis, gastric polyps, and gastric ulcer. Associations of HBV infection status or HBsAg seropositivity with Helicobacter pylori infection, atrophic gastritis and other high-risk events of gastric cancer were analyzed. Results: A total of 21,505 eligible observations were included, with Group C accounting for 6.1%. In Group C, the prevalence of gastric ulcer (p = 0.002) and very-high serum gastrin-17 level (p = 0.002) was significantly greater than in Group A. In multivariate analysis, both Helicobacter pylori infection (aOR = 2.79, 95% CI 2.44-3.21) and HBsAg seropositivity (aOR = 1.28, 95% CI 1.02-1.59) were significant risk factors for hypergastrinemia. No interaction was found between Helicobacter pylori co-infection risks and Group B (aOR = 1.10, 95% CI 0.84-1.43) or Group C (aOR = 1.40, 95% CI 0.66-2.95). Helicobacter pylori infection was identified as an independent risk factor for atrophic gastritis (aOR = 1.85, 95% CI 1.44-2.39). However, HBsAg seropositivity did not show a similar association with atrophic gastritis (aOR = 1.15, 95% CI 0.75-1.74). Moreover, HBV co-infection did not exert a synergistic effect on the risk of atrophic gastritis in individuals with Helicobacter pylori (aOR = 1.09, 95% CI 0.54-2.22). Additionally, multivariate analyses did not identify significant associations between HBV infection statuses and gastric polyps or ulcers. Conclusions: HBsAg seropositivity was not associated with increased risk of atrophic gastritis, gastric polyps or ulcers, or Helicobacter pylori infection, with the exception of hypergastrinemia. Additionally, HBV co-infection did not exert a synergistic effect on increasing the risk of atrophic gastritis in patients with Helicobacter pylori. Collectively, these findings suggest that the mechanism underlying the increased risk of gastric cancer in individuals with HBV may not be predominantly mediated via Helicobacter pylori infection and atrophic gastritis. Theories regarding HBV-induced genotoxicity or confounding effects warrant further investigation.