Abstract

Background: Given the close relationship between Helicobacter pylori (Hp) infection and gastric cancer, accurate diagnosis of Hp infection is important in subjects with high gastric cancer risk. At present, Hp infection is often diagnosed based on serum levels of antiH. pylori IgG antibody. However, this test is known to show false negatives for some patients. We investigated the characteristics of Hp in falsely sero-negative patients in relation to serum pepsinogen as a serum marker of gastric atrophy. Methods: A total of 276 outpatients at the University Hospital of Hamamatsu University School of Medicine who underwent gastroscopy for screening of Hp infection were enrolled. For diagnosis of Hp infection, PCR using gastric juice samples and culture tests were performed. Serum levels of pepsinogen I (PGI), pepsinogen II (PGII), and anti-H. pylori IgG antibodies (anti-Hp IgG) were measured. The ratios of PGl to PGII (PGI/PGII ratios) were calculated as a serological marker of gastric atrophy. A PGI/PGII ratio , 3.0 indicated severe gastric atrophy and increased gastric cancer risk. Samples with an anti-Hp IgG titer , 10 U/ml were diagnosed as sero-negative for Hp. If the PCR or culture test was positive, the subject was diagnosed as infected with Hp. However, if a subjects was positive based on only the PCR test, had a titer value of , 10 U/ml, and had no atrophy endoscopically, they were deemed false-positive for PCR and excluded from the analysis. Results: Of the 276 subjects, 6 were diagnosed as false-positive for PCR. Of the remaining 270, 24 were not infected with Hp or negative for anti-Hp IgG (Hp-/IgG-), 219 were infected with Hp and positive for anti-Hp IgG (Hp+/IgG+), 16 were infected with Hp but negative for negative for anti-Hp IgG (Hp+/IgG-) and therefore considered falsely sero-negative for Hp infection, and 11 were not infected with Hp but positive for anti-Hp IgG (Hp-/IgG+) and therefore considered falsely sero-positive for Hp infection. Serum PGI/PGII ratios in the Hp-/IgG-, Hp+/IgG+, Hp+/IgG-, and Hp-/IgG+ groups were 5.46, 2.55, 2.59, and 5.28 respectively. The mean of serum PGI/PGII ratios in the falsely sero-negative group was lower than those of the Hp-/IgGor Hp-/IgG+ groups (P ,0.001 and 0.003), and its subjects were considered to be at risk for severe gastric atrophy that was the same as that of the Hp+/IgG+ group. Of the 16 subjects, 15 were positive for the PCR test alone. Conclusion: The results of the present study suggest that individuals who are falsely sero-negative for Hp infection have high risk of severe atrophic gastritis. Although the serological test for Hp is a simple and easy assay for use in screening of Hp infection, it carries risk of false negatives. In contrast, the PCR method can cause false positives but can diagnose Hp infection in sero-negative subjects who are at high risk for gastric cancer.

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