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

<b>Background:</b> 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. <b>Aims:</b> The present study aimed to observe and evaluate associations between HBV infection with <i>Helicobacter pylori</i>, atrophic gastritis, and some other high-risk events for gastric cancer development. <b>Methods:</b> 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, <i>Helicobacter pylori</i> 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 <i>Helicobacter pylori</i> infection, atrophic gastritis and other high-risk events of gastric cancer were analyzed. <b>Results:</b> A total of 21,505 eligible observations were included, with Group C accounting for 6.1%. In Group C, the prevalence of gastric ulcer (<i>p</i> = 0.002) and very-high serum gastrin-17 level (<i>p</i> = 0.002) was significantly greater than in Group A. In multivariate analysis, both <i>Helicobacter pylori</i> 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 <i>Helicobacter pylori</i> 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). <i>Helicobacter pylori</i> 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 <i>Helicobacter pylori</i> (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. <b>Conclusions:</b> HBsAg seropositivity was not associated with increased risk of atrophic gastritis, gastric polyps or ulcers, or <i>Helicobacter pylori</i> 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 <i>Helicobacter pylori</i>. Collectively, these findings suggest that the mechanism underlying the increased risk of gastric cancer in individuals with HBV may not be predominantly mediated via <i>Helicobacter pylori</i> infection and atrophic gastritis. Theories regarding HBV-induced genotoxicity or confounding effects warrant further investigation.