PCR analysis and specific immunohistochemistry revealing a high prevalence of non‐Helicobacter pylori Helicobacters in Helicobacter pylori‐negative gastric disease patients in Japan: High susceptibility to an Hp eradication regimen

Abstract Background The clinical significance of non‐ Helicobacter pylori Helicobacter (NHPH) is still unknown. There are many reports of NHPH‐infected patients suffering from gastric diseases. Here, we investigated the polymerase chain reaction (PCR) positivity of NHPH infection in gastric disease patients who were negative for H. pylori (Hp) by the rapid urease test and by pathological observation. Materials and methods We collected the 296 endoscopically obtained gastric mucosal samples of Hp‐negative gastric disease patients diagnosed based on a rapid urease test and pathology from 17 hospitals in Japan from September 2013 to June 2019, and we analyzed the existence of Hp and NHPH by PCR. The samples were also treated by indirect immunohistochemistry using an anti‐ Helicobacter suis VacA paralog antibody and were observed by confocal laser microscopy. Results Among the 236 non‐Hp‐eradicated cases, 49 cases (20.8%) were positive for NHPH. Among them, 20 cases were positive for Helicobacter suis , 7 cases were positive for Helicobacter heilmannii sensu stricto/ Helicobacter ailurogastricus (Hhss/Ha), and the other 22 cases could not be identified. The regional differences in the infection rates were significant. Forty percent of the nodular gastritis cases, 24% of the MALT lymphoma, 17% of the chronic gastritis cases, and 33% of the gastroduodenal ulcer cases were NHPH positive. Forty‐five patients had been treated with one of the four types of combinations of a proton pump inhibitor and two antibiotics, and in all of these cases, the NHPH diagnosed by PCR was successfully eradicated. Immunohistochemistry using the Helicobacter suis ‐specific HsvA antibody coincided well with the PCR results. Among the 29 post‐Hp eradication cases, three were NHPH positive, including one Hhss/Ha‐positive case. Thus, approx. 20% of the Hp‐negative non‐Hp‐eradicated gastric disease patients treated at 17 hospitals in Japan were infected with NHPH.