Autoimmune Atrophic Gastritis Patients Research Articles

Autoimmune atrophic gastritis and coeliac disease: A case-control study.

Autoimmune atrophic gastritis (AAG) is rarely associated with coeliac disease (CD). To assess the frequency of AAG-CD association and to compare clinical, biochemical, and histological features of adults affected by both diseases (cases) with AAG controls. This case-control study included 9 cases (F55%, median age 47, range 23-59yrs) matched (1:3) by age (±4 yrs) and gender to 27 controls randomly selected from our AAG cohort (2009-2021). The AAG and CD diagnosis was based on internationally agreed criteria. Of 434 AAG patients (median age:62.5yrs, range18-92yrs, F:M ratio=2.2:1),9 had a concomitant diagnosis of CD. The occurrence of AAG-CD association was 2% and 1.65% among AAG/CD cohorts, respectively. Cases were significantly younger than AAG cohort (n=425, p=0.002). In 4/9cases, AAG was diagnosed by proactive screening for autoimmune disorders. Autoimmune thyroid disorders were present in 5/9 cases. Cases had a significant higher prevalence of normocytic anaemia than controls (p=0.004). No significant differences were found between cases and controls concerning clinical and histological features. AAG-CD association is rare. Gastric and duodenal biopsies might be advisable in young people with normocytic anaemia and associated autoimmune disorders to timely diagnose clinically silent conditions.

The Impact of Proton Pump Inhibitors on the Development of Gastric Neoplastic Lesions in Patients With Autoimmune Atrophic Gastritis.

IntroductionProton pump inhibitors (PPIs) have been widely prescribed as a primary treatment for acid-related disorders. A large body of literature reported several adverse outcomes due to PPI therapy, including an increased risk of gastric cancer (GC). Autoimmune atrophic gastritis (AAG) is a chronic inflammatory disorder affecting the oxyntic mucosa, leading to mucosal atrophy, intestinal metaplasia, and reduced gastric acid secretion, up to the possible development of dysplasia and intestinal-type GC. Whether PPI use may increase the GC risk in AAG patients has not yet been investigated. We conducted a case–control study in AAG patients to assess the association between the PPI use before AAG diagnosis and the development of GC at follow-up (FU).Materials and MethodsPatients were included from a prospective cohort of AAG patients (diagnosed 1992–2021) in a referral center for gastric autoimmunity; all patients adhered to an endoscopic–histological FU program according to Management of precancerous conditions and lesions in the stomach (MAPS) I/II (management of epithelial precancerous conditions) guidelines. At diagnosis, clinical/biochemical data and PPI use before AAG diagnosis (withdrawn at the time of diagnosis), for at least 12 months, were evaluated. Patients who developed gastric neoplastic lesions (GNLs) at FU were considered as cases; patients without a diagnosis of GNLs at FU were considered as controls. At a total FU of 2.3 years (1–13), 35 cases were identified, and controls were matched 2:1 by age ( ± 3 years), gender, and years of FU (n=70); therefore, a total of n=105 patients were included in the study.ResultsThe proportion of PPI users before AAG diagnosis was significantly higher in cases than in controls (54.3% vs. 18.6%, p<0.001). At logistic regression, considering as a dependent variable the development of GNLs at FU, a positive association was shown for PPI use before AAG diagnosis (OR 9.6, 95%CI 2.3–40.3), while other independent variables as the use of antiplatelets/anticoagulants (OR 2.8, 95%CI 0.7–12.0), age ≥ 50 years (OR 2.0, 95%CI 0.2–18.1), 1st-degree family history for GC (OR 2.4, 95%CI 0.4–15.2), and smoking habit (OR 0.4, 95%CI 0.1–2.1) were not associated.ConclusionsPPI use before the diagnosis of AAG appears to considerably increase the risk of subsequent GNL development. Considering the common misuse of PPIs, physicians should regularly reevaluate the appropriateness of ongoing PPI therapy, in particular in patients with a clinical suspicion of or already diagnosed AAG.

Gender-sex differences in autoimmune atrophic gastritis

Gender-sex differences in autoimmune diseases are gaining increasing attention due to their effects on prevalence and clinical features. Data on gender-sex differences in autoimmune atrophic gastritis (AAG), a chronic not-self-limiting inflammatory condition characterized by corpus-oxyntic mucosa atrophy sparing the antrum, are lacking. This study aimed to assess possible gender-sex differences of clinical, serological, histological, and genetic features in AAG patients. Cross-sectional study on 435 patients with histological-AAG, stratified according to female-male gender. In subsets of patients, serum gastric-autoantibodies against intrinsic-factor (IFA) and parietal-cells (PCA) by luminescent-immunoprecipitation-system (LIPS) (n=81) and of HLA-DRB1-genotyping (n=89) were available and stratified according to sex. Female AAG-patients were preponderant: 69.2%vs30.8%, P < 0.0001(ratio 2.2:1). Females were more frequently PCA and/or IFA-positive than males (90.9%vs73.1%, P=0.0361). HLA-DRB1*06-alleles were significantly more frequent in females [30%vs4%, P=0.01, OR 10.1(95%CI 1.3-80.4); HLA-DRB1*04-alleles were more frequent and HLA-DRB1*03 and *05-alleles less frequent in females without reaching statistical significance. At logistic regression, iron-deficiency-anemia [OR 3.6(95%CI 1.9-7.0)], body-mass-index <25m2/kg [OR 3.1(95%CI 1.7-5.6)], autoimmune-thyroid-disease [OR 2.5(95%CI 1.4-4.5), and dyspepsia [OR 2.4(95%CI 1.4-4.3) were significantly associated to females. Body-mass-index>25m2/kg [OR 3.2(95%CI1.8-5.6)], absence of autoimmune-thyroid-disease [OR 2.3(95%CI 1.3-4.2)] and dyspepsia [OR 2.1(95%CI 1.2-3.7)], smoking habit [OR 1.8(95%CI 1.1-3.1)], and pernicious-anemia [OR 1.7(95%CI 1.0-3.0)], were significantly associated to males. AAG was preponderant in women who showed stronger autoimmune serological responsiveness and different HLA-DRB1 association. AAG showed differential clinical profiles in female and male patients occurring mainly in normal weight, dyspeptic women with iron-deficiency anemia and autoimmune thyroid disease, but in overweight male smokers with pernicious anemia. Stratification for sex and gender should be considered in future genetic, immunological, and clinical studies on autoimmune atrophic gastritis.

Endoscopic diagnosis of gastric intestinal metaplasia in patients with autoimmune gastritis using narrow-band imaging: does pseudopyloric metaplasia muddy the waters?

Background and study aims In autoimmune atrophic gastritis (AAG), associated with intestinal (IM) and/or pseudopyloric metaplasia (PPM), endoscopic surveillance is recommended for gastric cancer risk mainly linked to IM. Endoscopic Grading of Gastric Intestinal Metaplasia (EGGIM) reliably identifies IM, but has not been assessed in AAG. We aimed to assess the performance of EGGIM (index test) versus histology (reference test) of corpus IM in AAG. Patients and methods This was a cross-sectional study of 210 AAG patients undergoing surveillance gastroscopy with narrow-band imaging (NBI): corpus IM scored according to EGGIM, histology according to updated Sydney system, and morphological criteria. Results NBI identified corpus IM in 88.6 % of AAG patients: EGGIM were 0, 1, 2, 3, 4 in 11.4 %, 0.5 %, 33.3 %, 1.9 %, and 52.9 %, respectively. Histology identified corpus IM in 78.1 % and PPM in 79.5 % of patients. PPM was present with IM in 57.6 % and without IM in 21.9 % patients, 20.5 % had IM without PPM. EGGIM, compared to histology, correctly classified 76.2 % of patients, showing high sensitivity (91.5 %, 95 %CI 86.1–95.3). EGGIM correctly classified 93 % of patients with IM without PPM, 90.9 % with both metaplasias, and 21.7 % with PPM without IM yielding low specificity (21.7 %, 95 %CI 10.9–36.4). Conclusions In AAG, EGGIM showed high accuracy and sensitivity identifying > 90 % of patients with histological corpus IM. EGGIM overestimated IM when PPM without IM was present, yielding low specificity. These findings raise the question of whether in AAG, PPM and IM may display similar endoscopic features on NBI.

Objective Evidence of Gastro-Esophageal Reflux Disease is Rare in Patients with Autoimmune Gastritis

Patients with autoimmune atrophic gastritis (AAG) often complain of acid reflux symptoms, despite the evidence of hypo-achlorhydria. Rome IV criteria are used to define functional esophageal disorders. Our aim was to characterize gastroesophageal reflux disease (GERD) phenotypes in patients with AAG. Between 2017-2018, 172 AAG patients were evaluated at Gastro-Oncology outpatient clinic of University of Padua. Of them, 38 patients with reflux symptoms underwent high-resolution manometry (HRM) and multichannel intraluminal impedance-pH monitoring (MII-pH). Seventy-six AAG consecutive patients asymptomatic for gastroesophageal reflux were selected as age and gender matched controls. Serum biomarkers (pepsinogens, gastrin-17 and Helicobacter pylori antibodies), upper endoscopy, histology and clinical data were compared. Out of 38/172 (22%) AAG patients with reflux symptoms, 2/38 had a GERD diagnosis based on abnormal esophageal acid exposure and 6/38 had a major motility disorder (i.e. outflow obstruction). Among the 30/38 patients with normal endoscopic findings, 9/30 had reflux hypersensitivity, 19 functional heartburn, 1 functional globus, 1 functional chest pain according to the Rome IV criteria. Antral atrophy, advanced corpus atrophy and OLGA stage were more frequent in controls than in reflux patients (p=0.01, p=0.031, p=0.01, respectively). No differences were found for serum biomarkers and symptom presentation. Most of the patients received proton pump inhibitors (PPIs) treatment (87%), with a minority (34%) reporting clinical benefit. Reflux symptoms are relatively common in AAG patients, but a firm diagnosis of GERD is rare (5%), whereas most of the patients have a functional disorder. PPI treatment is mostly clinical ineffective and should not be largely indicated.

Impaired Quality of Life in Patients with Autoimmune Atrophic Gastritis.

Autoimmune atrophic gastritis (AAG) leads to vitamin B12 deficiency that may manifest with neuropsychiatric disorders, such as emotional instability, cognitive deficits, depression, and personality changes. To evaluate the quality of life (QoL) in patients with AAG and the interplay between QoL, psychopathological symptoms, and demographic factors. This is an observational, cross-sectional study including 102 patients with AAG (mean age 62 ± 13years), 100 with functional gastrointestinal disorders (mean age 38.3 ± 17years), 100 with other chronic organic gastrointestinal diseases (mean age 50.9 ± 21.4years), and 100 healthy controls (mean age 37.5 ± 18.9years). The 36-Item Short Form Health Survey questionnaire (SF-36) and the General Health Questionnaire-12 were administered. The results of the scales were compared among the study groups. Linear regression analyses were fitted to identify independent predictors of QoL in AAG patients. QoL was significantly different among the four groups in all subdomains. In particular, the AAG group was significantly (P < 0.01) more impaired than the functional gastrointestinal disorder group in the physical functioning and it was significantly more impaired than the control group in all the quality of life subdomains with exception of vitality. Vitamin B12 serum level was a significant (P < 0.04) independent predictor of physical functioning. Patients with AAG have a decreased QoL compared to healthy controls, but in line with that of patients with organic gastrointestinal disorders. Physical component is responsible for worsening QoL. Vitamin B12 supplementation may positively affect patient's perception of body functioning.

Duodenal Histological Findings and Risk of Coeliac Disease in Subjects with Autoimmune Atrophic Gastritis: A Retrospective Evaluation

Background and Aim: Autoimmune atrophic gastritis (AAG) is characterized by a variable spectrum of gastric and extra-gastric symptoms and has been associated with other autoimmune diseases. It is still unknown whether AAG patients have a higher risk of coeliac disease (CeD) or of any other particular duodenal histological damage. Our study aimed at evaluating the duodenal histological findings and the risk of CeD in patients with AAG, with and without other concurrent autoimmune diseases. Methods: We retrospectively collected all the histological findings of the adult patients undergoing upper gastrointestinal endoscopy with concurrent duodenal and gastric biopsies at our gastroenterology unit between 2015 and 2018 and who were regularly followed up at our centre. Date of endoscopy evaluation, endoscopy indication, data on previous CeD diagnosis and on other autoimmune-associated diseases, and a description of histological diagnosis were recorded. Results: Of the 2,423 evaluated endoscopies, 209 patients had an AAG diagnosis (8.6%). One hundred thirty-nine patients, aged 57.4 (standard deviation 13.2) years, were regularly followed up at our centre and were included. Of them, 4 subjects had a previous diagnosis of CeD and one had CeD diagnosis at index endoscopy. Additionally, 8 patients had an isolated increase of intraepithelial lymphocytes (IELs, 6%) and 2 villous atrophy with a normal IEL count. The risk of CeD in AAG was not modulated by the presence of other concurrent autoimmune diseases. Conclusions: We support the screening of all AAG patients with CeD autoantibodies. Findings of isolated IEL or villous atrophy are not exclusively related to CeD.

Cell Blood Count Alterations and Patterns of Anaemia in Autoimmune Atrophic Gastritis at Diagnosis: A Multicentre Study.

Background: Autoimmune atrophic gastritis (AAG) leads to iron and/or vitamin B12 malabsorption, with subsequent haematological alterations which could represent the sole clinical manifestation. We aimed to assess patterns of anaemia and micronutrient deficiencies in patients with AAG at the time of diagnosis. Methods: Observational, multicentre, cross-sectional study including consecutive adult patients diagnosed with AAG within the last ten years. Cell blood count, red cell distribution width, serum vitamin B12, and ferritin were collected. Multivariate analysis for predictive factors of anaemia was computed. Results: 654 AAG patients (mean age 59.2 ± 13.8 years, female (F): male (M) ratio = 2.3:1) were included. Anaemia was present in 316 patients (48.3%; mean age 60.1 ± 15.8 years, F:M ratio = 2.3:1). Pernicious anaemia (132/316 cases, 41.7%) was more common in males (27.1% versus 12.4%; p = 0.001) and in older patients (63.0 ± 14.6 versus 58.9 ± 14.9 years; p = 0.014), while iron deficiency anaemia (112/316 cases, 35.4%) was more common in females (16.9% versus 10.0%; p = 0.039) and in younger patients (56.8 ± 16.6 versus 60.2 ± 14.6 years; p = 0.043). The prevalence of iron deficiency was equally distributed between anaemic and non-anaemic patients (p = 0.9). Anisocytosis (odds ratio: 10.65, 95% confidence interval: 6.13–18.50, p < 0.0001) was independently associated with anaemia. Conclusions: Anaemia is a common manifestation in AAG patients, mostly due to micronutrient deficiencies. Scant haematologic alterations and micronutrient deficiencies may precede overt anaemia.

Natural history of autoimmune atrophic gastritis: a prospective, single centre, long-term experience.

Autoimmune atrophic gastritis (AAG) is an immune-mediated disorder characterised by destruction of gastric oxyntic mucosa AIM: To explore gastric histopathological evolution in a cohort of AAG patients over a prolonged follow-up METHODS: Single centre prospective study enrolling consecutive patients with histologically confirmed AAG between 2000 and 2018. All AAG patients undergoing endoscopic follow-up every 1-3years were classified as having stages 1, 2 or 3 according to atrophy severity (mild, moderate and severe). AAG patients with either glandular or neuroendocrine dysplasia/neoplasia were classified as having stage 4. Disease stage progression, and changes in serum anti-parietal cell antibody (PCA), chromogranin A and gastrin-17 were assessed. In total, 282 AAG patients (mean age 60.3years; F:M ratio 2.4:1; median follow-up 3years, interquartile range 1-7) were enrolled. All patients with stages 1 or 2 progressed to stage 2 or 3 over time with a steady trend (P=.243) and regression from a severe to a milder stage was never noticed. Disease progression of patients with stages 1 or 2 occurred within the first 3years. PCA positivity rate did not change over time. Stage 3 patients had higher gastrin-17 levels compared to patients with stages 1 and 2 (median 606 vs 295pg/mL; P<.001). In stage 3, the hazard ratio for the risk of developing stage 4 was 6.6 (95% CI 1.5-29; P=.001). AAG is a steadily progressive disease, in which stages 1 and 2 always progress to stage 3. The risk of developing a complicated disease stage is greater in patients with more severe gastric lesions.

271 Cathelicidin Inhibits Colitis Associated Colon Cancer Development by Inhibition of Epithelial-Mesenchymal Transition and Cancer Associated Fibroblasts

Oxyntic atrophy and intestinal metaplasia are considered critical precursors for the development of gastric adenocarcinoma. Autoimmune atrophic gastritis (AAG) is characterized by immune-mediated destruction of gastric parietal cells, chronic inflammation, atrophic gastritis, and pernicious anemia. While AAG is associated with increased risk of carcinoids, the risk for adenocarcinoma in the absence of H. pylori infection is controversial. Here, we investigated the differences between AAG and chronic atrophic gastritis (CAG) with intestinal metaplasia (IM). Methods: Tissue from 6 patients with CAG were obtained at the time of resection for gastric adenocarcinomna and all patients showed IM. 20 AAG patients were diagnosed by upper endoscopy, oxyntic atrophy, and the presence of anti-parietal cell antibodies. 20/20 AAG patients were negative for H. pylori. 19/20 AAG patient showed marked elevations in both serum gastrin and serum chromogranin. In the body mucosa, we evaluated the presence of spasmolytic-polypeptide expressing metaplasia (SPEM) with TFF2 staining, IM with MUC2, macrophages with CD68, neutrophils with myeloperoxidase (MPO) and proliferative cells with Ki67. Results: 20/20 AAG patients showed profound parietal cell loss with SPEM and 15 demonstrated IM (75%). AAG patients had significantly fewer MPO positive neutrophils (6.4/1000 cells) compared to CAG patients (21.9/1000 cells) (p<0.01). The gastric biopsies from AAG patients also showed significantly fewer CD68 positive macrophages (10.1/1000 cells) compared to CAG patients (17.4/1000 cells, p= 0.01). Ki67 positive cells were markedly decreased in AAG patients (0.2/1000 cells) compared to CAG patients (14.5/1000 cells) (p<0.01). Conclusions: The metaplasia observed in AAG patients exhibited a low proliferative rate compared with the metaplasia samples from CAG patients. This lower proliferative rate was associated with smaller macrophage and neutrophil numbers in AAG patients compared to those in CAG patients. The lower proliferative rate in metaplasia and reduced macrophage and neutrophil infiltrates may explain in part the lower tendency of metaplasia in H. pylori-negative AAG patients to evolve into gastric adenocarcinoma compared with individuals with CAG.

Occurrence ofBifidobacteriaceaein human hypochlorhydria stomach

BackgroundThe human stomach, when healthy, is not a suitable host for microorganisms, but in pathological conditions such as gastritis, when gastric acid secretion is impaired, microbial overgrowth can be observed. Apart from Helicobacter pylori, the composition of microbiota, resident or exogenously introduced during neutral/high pH conditions, has not been investigated thoroughly. Thus, it is possible that Bifidobacteriaceae, important autochthonous and beneficial bacteria of human gastrointestinal microbiota, could over-colonize the stomach of hypochlorhydria patients suffering from autoimmune atrophic gastritis (AAG) or omeprazole-treated (OME) gastritis. This prompted us to characterize the Bifidobacteriaceae in such patients’ gastric microbiota and to study its abnormal colonization.MethodsSamples of gastric juices, and antrum and corpus mucosa from 23 hypochlorhydria patients (13 AAG and 10 OME) and from 10 control volunteers with base-line normochlorhydria, were cultivated in Brain Heart Infusion (BHI) and selective Bifidobacterium-Tryptone-Phytone-Yeast extract (Bif-TPY) media. The isolates were characterized by the fructose-6-phosphate phosphoketolase (F6PPK) test, electrophoresis of cellular proteins, the fermentation test, guanine-cytosine% DNA content, and DNA–DNA hybridization. Negative F6PPK isolates were characterized by order-specific polymerase chain reaction (PCR).ResultsA total of 125 isolates, assigned to the Bifidobacteriaceae family on the basis of their morphology, were obtained from AAG and OME patients, but not from normal subjects. Of these isolates, 55 were assigned to the Bifidobacteriaceae family on the basis of their fructose-6-phosphoketolase (PPK) activity, PPK being the key taxonomic enzyme of this family. The remaining 70 isolates, which were PPK-negative, were attributed to the Actinomycetales order following specific primer PCR analysis. We observed a significantly higher abundance of Bifidobacteriaceae (Bifidobacterium dentium, Scardovia inopinata, and Parascardovia denticolens) in OME group than the AAG group. Furthermore, the Actinomycetales distribution was homogeneous for both hypochlorhydria patient groups.ConclusionsThis study suggests that the Bifidobacteriaceae species, typically found in the oral cavity, readily colonizes the hypochlorhydria stomach of OME patients. The clinical relevance and the mechanism underlying this Bifidobacteriaceae presence in OME gastritis requires further functional studies.

Immunoblotting reveals signs of infection in all autoimmune atrophic gastritis patients

Immunoblotting reveals signs of infection in all autoimmune atrophic gastritis patients