Helicobacter-negative Chronic Active Gastritis Is a Distinct Nosologic Entity, Not Simply Missed Helicobacter Infection

Abstract

Purpose:Helicobacter-negative chronic active gastritis (HNCAG) is a histopathologic entity characterized by diffuse chronic active inflammation in a pattern typically encountered in H. pylori gastritis, but with no organisms detectable. A recent study found no evidence to support any of the most commonly offered hypotheses: sampling error, recent use of antibiotics, and effects of proton pump inhibitors (Nordenstedt et al., Am J Gastroenterol 2012). The purpose of this study was to determine whether the epidemiologic patterns of HNCAG were sufficiently different from those of H. pylori gastritis, providing additional evidence that the two entities are unrelated. Methods: We extracted histopathologic and demographic information from the Miraca Life Sciences database for all patients with gastric biopsies (1.2008-6.2012). We then selected two groups: patients from zip codes where the mean tissue prevalence of H. pylori infection was ≤6% (“low-prevalence”) and those from zip codes with a mean prevalence of ≥12% (“high-prevalence”). Each group was then stratifi ed in eight age groups and the relative prevalence of H. pylori gastritis and HNCAG were compared in each age group. Results: From 596,480 unique patients with gastric biopsies (median age 57 years; 62% female), we extracted 79,874 subjects from low-prevalence areas (median age 57 years; 60.8% female) and 156,445 subjects from high-prevalence areas (median age 61.9 years; 61.9% female). Figure 1 shows that in high-prevalence areas, H. pylori infection increased from 14.5% in children to a maximum of 21% in the fifth decade, and declined to 13.8% after age 80 years; in low-prevalence areas, H. pylori infection increased steadily in each decade, from 2.8% in children to 6.0% in subjects older than 80 years. In contrast, HNCAG increased with age in an identical fashion among subjects from both areas, to reach a maximum prevalence of 3.8%.FigureConclusion: If HNCAG represented “missed infections” (i.e., cases of H. pylori gastritis in which organisms could not be detected), one would expect its prevalence and demographic distribution to parallel that of H. pylori gastritis. Instead, the distribution of HNCAG is virtually identical in the two groups and appears unrelated to the prevalence of H. pylori. These findings provide strong support to the concept that HNCAG is a distinct condition, unrelated not only to H. pylori infection, but also to the socioeconomic factors associated with it.