Associations between hepatitis B virus infection and precancerous high-risk events of gastric cancer: a cross-sectional study (SIGES)

<h2>Abstract</h2><h3>Background</h3> Hepatitis B Virus (HBV) infection is a global public health issue, and China is also one of the epidemic areas of HBV infection. Studies found HBV infected individuals, especially with hepatitis B virus surface antigen (HBsAg) positive, might increase risk of gastric cancer. Whether precancerous high-risk events are associated with HBV infection needs further investigation. <h3>Methods</h3> This cross-sectional study collected health check-up observations (18-75 years old) at the Health Management Center, West China Hospital of Sichuan University between 2018 and 2020. Data including demographic information (sex, age, ethnicity, education, body mass index, smoking, alcohol drinking, and family history of cancer), serological test results, i.e. gastrin-17 (G-17), pepsinogen-I (PG-I), pepsinogen-II (PG-II), HBV associated antigens and antibodies, Helicobacter pylori (Hp) infection, magnetically controlled capsule gastroscopy (MCCG) outcomes were retrieved. Observations were divided into three groups according to HBV infection status: Group A was not infected with HBV; Group B was past infection with HBV; and Group C was inactive HBsAg carriers or active HBV infected people (i.e., HBsAg positive). Associations between HBV infection and the incidence of precancerous high-risk events of gastric cancer and risk factors were analyzed in univariate and multivariate manners. Precancerous high-risk events included comorbidity with chronic gastritis, history of gastric ulcer, Hp infection, serological atrophic gastritis, high level of serum G-17, as well as atrophic gastritis, gastric polyps, and gastric ulcer by MCCG. <h3>Findings</h3> A total of 21,505 eligible observations were analyzed (Group B: 54.3% and Group C: 6.1%). When compared baselines to Group A, demographic characteristics of Group B and Group C were variously and significantly different, except family history of cancer (p=0.918) in Group B, while except ethnicity (p=0.061) and alcohol drinking status (p=0.316) in Group C. In Group B, the incidence of comorbidity with chronic gastritis (33.9‰ vs. 25.0‰, p<0.001), serologic atrophic gastritis (18.7‰ vs. 13.9‰, p=0.008), and very-high serum G-17 level (28.6‰ vs. 20.9‰, p<0.001) were significantly higher than those in Group A. In Group C, the incidence of gastric ulcer (74.1‰ vs. 7.9‰, p=0.002), and very-high serum G-17 level (28.9‰ vs. 20.9‰, p=0.002) were significantly higher than those in Group A. Univariate and multivariate analyses showed that Hp infection was an independent risk factor for serologic atrophic gastritis (aOR=1.85, 95% CI 1.44-2.39), but HBsAg positive not (aOR=1.15, 95% CI 0.75-1.74). HBV co-infection did not increase the risk of serological atrophic gastritis among Hp-infected persons (oOR=1.09, 95% CI 0.54-2.22). Hp-infected (aOR=2.79, 95% CI 2.44-3.21) and HBsAg-positive (aOR=1.28, 95% CI 1.02-1.59) were potential risk factors for high serum G-17 levels, but no additional synergistic effect HBV co-infection among Hp-infected persons (aOR=1.06, 95% CI 0.74-1.52). <h3>Interpretation</h3> The past HBV infection had an increased risk of chronic gastritis and serologic atrophic gastritis, while HBsAg positive persons had an increased risk of gastric ulcer. Serum G-17 levels were significantly increased in past HBV infection and HBsAg positive persons. It might be the potential explanation of association between HBV infection and increased risk of gastric cancer, which still needs further investigation.