Gastric cancer in patients with Helicobacter pylori-negative autoimmune gastritis

Although Helicobacter pylori (H. pylori) is implicated in the development of most cases of gastric cancer with autoimmune gastritis, cases of gastric cancer have been reported in patients testing negative for H. pylori. Here, we aimed to outline the current research status of the factors involved in the development of gastric cancer in H. pylori-negative autoimmune gastritis. Predictive pathological conditions for the development of gastric cancer in H. pylori-negative autoimmune gastritis are postulated to be: (1) Severe atrophy; (2) Hypergastrinemia; (3) Bile reflux; and (4) Low acidity, which are directly related to the pathophysiology of autoimmune gastritis, as well as smoking and family history, which are not related to autoimmune gastritis. In autoimmune gastritis, where there is a possibility of spontaneous disappearance of H. pylori in advanced atrophy, it is difficult to assess H. pylori. Since H. pylori infection begins in the antrum and subsequently progresses to the proximal stomach, it is interpreted as H. pylori-negative autoimmune gastritis if histologically consistent with autoimmune gastritis in the body with spared antrum, and negative for other H. pylori tests. However, it is essential to examine whether the currently prevailing histological interpretation used to evaluate H. pylori infection status is appropriate.