Esophagus to Small Intestine

Gut. 2023;72(1):30–8

Rugge M, Bricca L, Guzzinati S, Sacchi D, Pizzi M, Savarino E, Farinati F, Zorzi M, Fassan M, Dei Tos AP, Malfertheiner P, Genta RM, Graham DY

Autoimmune gastritis: Long-term natural history in naive Helicobacter pylori-negative patients


Objective: Autoimmune gastritis (AIG) is an immunomediated disease targeting parietal cells, eventually resulting in oxyntic-restricted atrophy. This long-term follow-up study aimed at elucidating the natural history, histological phenotype(s), and associated cancer risk of patients with AIG consistently tested Helicobacter pylori-negative (naive H. pylori-negative subjects).
Design: 211 naive H. pylori-negative patients (tested by serology, histology, molecular biology) with AIG (F:M = 3.15:1; p < 0.001) were prospectively followed up with paired biopsies (T1 vs. T2; mean follow-up years: 7.5 ± 4.4; median: 7). Histology distinguished non-atrophic versus atrophic AIG. Atrophy was further subtyped/scored as non-metaplastic versus metaplastic (pseudopyloric [PPM] and intestinal [IM]). Enterochromaffin-like cell (ECL) status was categorized as diffuse versus adenomatoid hyperplasia/dysplasia, and type 1 neuroendocrine tumors (Type1-NETs).
Results: Over the long-term histological follow-up, AIG consistently featured oxyntic-predominant-mononuclear inflammation. At T1, PPM score was greater than IM (200/211 vs. 160/211, respectively); IM scores increased from T1 to T2 (160/211 to 179/211), with no changes in the PPM prevalence (T1 = 200/211; T2 = 201/211). At both T1/T2, the prevalence of Operative Link on Gastritis Assessment (OLGA)-III-stage was < 5%; no OLGA-IV-stage occurred. ECL-cell status progressed from diffuse to adenomatoid hyperplasia/dysplasia (T1 = 167/14 vs. T2 = 151/25). Type1-NETs (T1 = 10; T2 = 11) always coexisted with extensive oxyntic-atrophy, and ECL adenomatoid hyperplasia/dysplasia. No excess risk of gastric or other malignancies was found over a cumulative follow-up time of 10,541 person-years, except for (marginally significant) thyroid cancer (standardized incidence ratio = 3.09; 95% confidence interval: 1.001–7.20).

Conclusions: Oxyntic-restricted inflammation, pseudopyloric metaplasia (more than intestinal metaplasia), and enterochromaffin-like cell hyperplasia/neoplasia are the histological autoimmune gastritis (AIG) hallmarks. Compared with the general population, corpus-restricted inflammation/atrophy does not increase the gastric cancer (GC) risk. The excess of GC risk reported in patients with AIG could plausibly result from unrecognized previous/current Helicobacter pylori comorbidity.

Prof. Dr. M. Rugge, Department of Medicine – DIMED, Universita degli Studi di Padova, Padova, Italy,
E-Mail: massimo.rugge@unipd.it

DOI: 10.1136/gutjnl-2022-327827

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