Incidence and risk factor of fundic gland polyp and hyperplastic polyp in long-term proton pump inhibitor therapy: a prospective study in Japan

To investigate the development of fundic gland polyp (FGP) and gastric hyperplastic polyp (HPP) during long-term proton pump inhibitor (PPI) therapy and risk factors of each polyp via patient status in a multicenter prospective study. The risk of developing FGP may increase during long-term PPI therapy. However, the association with PPI-induced hypergastrinemia is unclear. Helicobacter pylori (Hp) infection (which there is a high rate of in Japan) may influence the development of HPP. Reflux esophagitis patients on PPI maintenance therapy were enrolled. At baseline, the presence of protruding lesion (gastric polyps) and mucosal atrophy was examined endoscopically. The serum gastrin level (SGL) and Hp infection status were noted. The patients took rabeprazole 10 mg/day for 104 weeks and endoscopy was performed at weeks 24, 52, 76, and 104 to check for newly developed FGPs and HPPs. The hazard ratios (HRs) of risk factors were calculated. 191 patients were analyzed. The distribution of patients with baseline SGLs (pg/mL) of < 200, a parts per thousand yen200 to < 400, and a parts per thousand yen400 was 118 (61.8%), 51 (26.7%), and 22 (11.5%), respectively. 78 (40.8%) patients were Hp-positive, and gastric polyps were found in 70 (36.6%) patients. By the end of rabeprazole therapy, 26 (13.6%) and 17 (8.9%) patients had developed new FGPs and HPPs. In terms of risk factors, Hp-positive was significantly lower (HR = 0.288; 95% CI, 0.108-0.764) for FGP while SGL a parts per thousand yen400 pg/mL was significantly higher (HR = 4.923; 95% CI, 1.486-16.31) for HPP. During long-term PPI therapy, FGP development was associated with absence of Hp infection. Meanwhile, Hp infection and high SGL may influence HPP development.