Helicobacter Infection Research Articles

Helicobacter-negative gastritis: a distinct entity unrelated to Helicobacter pylori infection.

Helicobacter-negative gastritis is diagnosed when no organisms are detected in a gastric mucosa with typical features of Helicobacter gastritis (Hp-gastritis). If Helicobacter-negative gastritis consisted mostly of 'missed' Helicobacter infections, its prevalence should represent a constant percentage of these infections in a population, and their clinico-epidemiological features would overlap. To compare the epidemiologic patterns of Hp-positive and Hp-negative gastritis. From a pathology database, we extracted demographic, clinical and histopathological data from patients with gastric biopsies (1.2008-12.2013). We allocated patients to high (≥12%) and low (≤6%) H.pylori prevalence regions defined by ZIP code-based data. The prevalence of H.pylori-positive and -negative gastritis by sex, age and state were expressed as a per cent of the total study population stratified accordingly. Of 895323 patients, 10.6% had Hp-gastritis and 1.5% Helicobacter-negative gastritis. Hp-gastritis, but not Helicobacter-negative gastritis, was more common in males than females (OR 1.17, 95% CI: 1.16-1.19). While Hp-gastritis was more prevalent in high than in low-prevalence areas (OR 3.65, 95% CI: 3.57-3.74), Helicobacter-negative gastritis was only minimally affected by the underlying H.pylori prevalence (1.7% vs. 1.5%). The age-specific prevalence of Hp-gastritis peaked in the 4th to 5th decades; Helicobacter-negative gastritis exhibited a low and relatively flat pattern. The geographic distribution of H.pylori-positive and -negative gastritis showed no significant correlation. Intestinal metaplasia was found in 13.0% of patients with Hp-gastritis and in 6.1% of those with Helicobacter-negative gastritis (OR 0.43, 95% CI: 0.40-0.47). These data suggest that Helicobacter-negative gastritis is, in the vast majority of cases, a nosologically and epidemiologically distinct entity that deserves further investigation.

Gastric Helicobacter pylori infection associated with risk of diabetes mellitus, but not prediabetes.

The association between Helicobacter pylori infection and diabetes was inconsistent in previous studies. Moreover, there are no studies on the relationship between H. pylori infection and prediabetes in the literature. The aim of this study is thus to assess the association of Helicobacter infection, diagnosed by pathology from gastric biopsy, with diabetes and prediabetes. This cross-sectional study included 1285 subjects aged 19-85 who underwent esophagogastroduodenoscopy and gastric biopsy during health examinations at National Cheng Kung University Hospital from 2000 to 2009. Subjects were divided into three groups, including normal glucose tolerance, prediabetes, and diabetes. Diabetes and prediabetes were assessed according to the American Diabetes Association diagnostic criteria. Gastric Helicobacter infection was an independent variable. Chi-square tests, analysis of variance, and multinomial logistic regression models were used to analyze the effects of Helicobacter infection on the risk of diabetes and prediabetes while controlling for age, lifestyle, pathological conditions, and laboratory variables. There were significant differences in the prevalence of gastric Helicobacter infection among the three groups. The results of multivariate analysis showed that age, obesity, family history of diabetes, hypertension, and hypertriglyceridemia were significantly related to both prediabetes and diabetes. Helicobacter pylori infection was positively associated with diabetes (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.01-2.01), but not prediabetes (OR 1.02, 95% CI 0.77-1.36), in addition to male gender, education level (≤ 9 vs > 12 years), pre-hypertension, and low high-density lipoprotein cholesterol. Gastric H. pylori infection is associated with diabetes, but not prediabetes.

Histomorphological changes in gall bladder diseases and its association with helicobacter infection

Background: Gall bladder diseases can be an incidental finding and when symptomatic, present with signs and symptom of cholecystitis and cholelithiasis. On histopathological examination however wide range of pathological changes are encountered including carcinoma. Several studies have been carried out to establish relationship of helicobacter infection with gallbladder diseases. This study tries to look at the frequency of risk factors, spectrum of histological changes and the relationship between different types of gallbladder diseases and helicobacter infection.Materials and Methods: Total of 500 gallbladder specimen received over the period of 24 months was included in the study. Bile culture and histopathological examination cholecystectomy were performed with routine hematoxylin and eosin stain and Giemsa stain.Results: Out of the 500 cases. Helicobacter was seen in 166(33%) of cases. Carcinoma was seen in 7 (1%) cases. Helcobacter infection was seen positive in 5/7 (71%) malignant cases which showed a statistically significant p value of 0.03.Conclusion: Cholecystitis is the most common gallbladder disease. All gallbladder carcinomas were incidental finding and were of lower grade and stage. Helicobacter infection was prevalent in variety of gallbladder pathology and had significant association with gallbladder carcinoma. However, definite relation between the helicobacter infection and gallbladder diseases cannot be concluded. DOI: http://dx.doi.org/10.3126/jpn.v4i8.11607 Journal of Pathology of Nepal; Vol.4,No.8 (2014) 617-622

Helicobacter Infection and Chronic Liver Diseases

Abstract This paper reviews the recent Helicobacter infection associated with chronic liver disease. The bacteriology, prevalence, pathogenesis and diagnosis were reviewed. Future work should be conducted on the pathogenesis and treatment of this disease.

Evolving patterns in the diagnosis of reactive gastropathy: Data from a prospective Central European multicenter study with proposal of a new histologic scoring system

Histologic examination of gastric biopsies is crucial for determining the cause of gastritis. This prospective multicenter study was undertaken to investigate different histologic parameters arguing in favor or against the diagnosis of reactive gastropathy and to correlate findings with patient's symptoms and endoscopic findings. A total of 1123 individuals aged 15–93 years participated in a prospective multicenter study (histoGERD trial). Diagnosis of Helicobacter gastritis was made following the Updated Sydney System. Diagnosis of reactive gastropathy was based upon Dixon's parameters of foveolar hyperplasia, smooth muscle fibers in the lamina propria and vasodilatation and congestion of mucosal capillaries. Including paucity of acute and chronic inflammatory cells in analysis, a new score with visual analog scales for the diagnosis of reactive gastropathy was developed. All three histologic parameters in favor of the diagnosis of reactive gastropathy were positively associated with the endoscopic diagnosis of gastritis (p<0.001), yet negatively with Helicobacter infection (p<0.001). In contrast, presence of acute and chronic inflammatory cells in lamina propria was positively associated with Helicobacter infection (p<0.001), yet not with the endoscopic diagnosis of gastritis. Our score demonstrated strong association between histologic and endoscopic diagnoses (p<0.001), yet not with patient's symptoms. In conclusion, our data prove foveolar hyperplasia, smooth muscle fibers and vasodilatation and congestion as key histologic parameters for the diagnosis of reactive gastropathy. The proposed score may enhance the diagnostic accuracy. It should be validated in future studies.

Interferon-γ-producing B cells induce the formation of gastric lymphoid follicles after Helicobacter suis infection.

Helicobacter (H.) suis is capable of infecting various animals including humans, and H. suis infections can lead to gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Recently, we reported that interferon-γ (IFN-γ) was highly expressed in the stomachs of H. suis-infected mice, but the direct relationship between the upregulation of IFN-γ expression and the formation of gastric lymphoid follicles after H. suis infection remains unclear. Here, we demonstrated that the IFN-γ produced by B cells plays an important role in the formation of gastric lymphoid follicles after H. suis infection. In addition, IFN-γ-producing B cells evoked gastric lymphoid follicle formation independent of T-cell help, suggesting that they are crucial for the development of gastric MALT induced by Helicobacter infection.

Cardiac mucosa at the gastro-oesophageal junction: indicator of gastro-oesophageal reflux disease? Data from a prospective central European multicentre study on histological and endoscopic diagnosis of oesophagitis (histoGERD trial)

The origin and significance of cardiac mucosa at the gastro-oesophageal junction are controversial. In the prospective Central European multicentre histoGERD trial, we aimed to assess the prevalence of cardiac mucosa, characterized by the presence of glands composed of mucous cells without parietal cells, and to relate its presence to features related to gastro-oesophageal reflux disease (GORD). One thousand and seventy-one individuals (576 females and 495 males; median age 53 years) were available for analysis. Overall, in biopsy specimens systematically taken from above and below the gastro-oesophageal junction, cardiac mucosa was observed in 713 (66.6%) individuals. Its presence was associated with patients' symptoms and/or complaints (P = 0.0025), histological changes of the squamous epithelium (P < 0.001) indicative of GORD, intestinal metaplasia (P < 0.001), and an endoscopic diagnosis of oesophagitis (P < 0.001). No association with an endoscopic diagnosis of Barrett's oesophagus or with gastric pathology, particularly Helicobacter infection, was observed. Cardiac mucosa is a common finding in biopsy specimens taken from the gastro-oesophageal junction. Its association with reflux symptoms, histological changes indicating GORD and the endoscopic diagnosis of oesophagitis suggests that injury and repair related to GORD contribute to its development and/or expansion.

DNA methylation status of a distinctively different subset of genes is associated with each histologic Lauren classification subtype in early gastric carcinogenesis.

DNA methylation change is known to play a crucial role in early gastric carcinogenesis. The present study aimed to identify and validate the correlation between differentially methylated regions (DMRs) and the subtypes of early gastric cancers (EGCs). Illumina Infinium methylation assay (IIMA; 450K BeadChip kit) was performed on fresh tumor and non‑tumor tissues of 12 EGCs to screen the methylation status of 450,000 CpG sites. To evaluate the significance of DNA methylation in each histologic subtype, pyrosequencing assay (PA) was performed on 38 EGCs (18 intestinal-, 12 mixed- and 8 diffuse-type) using 12 genes selected from the screening. Between tumors of the intestinal-type (n=6), and diffuse- (n=4) plus mixed-types (n=2), 169 regions showed significant differences (intensity>3,000, Δβ>0.2) in IIMA. Hierarchical clustering using the 169 DMRs revealed distinct separation between the two groups. In PA using 12 selected genes from the IIMA results, the aberrant methylation statuses of DVL2 (p=0.0186) and ETS1 (p=0.0222) were significantly related to diffuse- and mixed-types rather than the intestinal-type, while C19orf35 (p=0.019) and CNRIP1 (p=0.0473) were related to the diffuse‑type rather than intestinal‑type, and GAL3ST2 (p=0.0158) and ITGA3 (p=0.0273) were related to the mixed-type rather than the other two types. The methylation of other genes, CLIP4, XKR6, CCDC57, MAML3 and SDC2, was related with age, tumor location, or Helicobacter infection rather than the histologic subtype. Aberrant DNA methylation of certain genes may be independently involved in each histologic subtype of EGC. Furthermore, mixed-type EGCs may be a distinctive histologic subtype based on the different subset of DMRs compared to those of other subtypes.

Treatment of Helicobacter Pylori in Children

Childrenwith Helicobacter infection need treatment. The aim of treatment is elimination of H.Pylori. Most patients with this infection are asymptomatic and without peptic disease. Treatment and management of these patients are controversy. Conventional Treatment: The best treatment for H. pylori eradication regimens should have cure rates of at least 80%, be without major side effects, and induce minimal bacterial resistance. Antibiotics alone have not achieved this. Luminal acidity influences both the effectiveness of some antimicrobial agents and the survival of the bacteri; thus antibiotics have been combined with acid suppression such as proton pump inhibitors (PPIs), bismuth, or H2 antagonists. The “classic” regimen is treatment twice daily for 7 days with a PPI and clarithromycin plus either amoxicillin or metronidazole Bismuth has been used in the treatment of peptic ulcer disease and 1 part o quadruple therapy for H.Pylori but compliance of children for it is low. Sequential Therapy Sequential therapyinvolves dual therapy with a PPI and amoxicillin for 5 days followed sequentially by clarithromycin, Tinidazole and omeperazole for 5 days or other triple therapy for 7 days. This treatment has had 97% efficacy. Adjunctive Therapies A number of studies have showed the potential benefits of probiotic therapy in H. pylori treatment regimens.Consumption of these drugs accompanied with other medications increase H.Pylori eradication.

Molecular Changes Leading to Gastric Cancer: A Suggestion From Rare-Type Gastric Tumors With GNAS Mutations

Molecular Changes Leading to Gastric Cancer: A Suggestion From Rare-Type Gastric Tumors With GNAS Mutations

Anti-CXCL13 antibody can inhibit the formation of gastric lymphoid follicles induced by Helicobacter infection.

Helicobacter suis infects the stomachs of both animals and humans, and can induce gastric mucosa-associated lymphoid tissue (MALT) lymphomas. It is known that CXC chemokine ligand 13 (CXCL13) is highly expressed in the Helicobacter-infected mice and gastric MALT lymphoma patients, but the pathway that links the activation of CXCL13 and the formation of gastric MALT lymphomas remains unclear. In this study, we examined whether CXCL13 neutralization would interfere with the formation of gastric lymphoid follicles including B cells, CD4+T cells, dendritic cells (DCs), and follicular DCs (FDCs) in germinal centers to determine the role of CXCL13 in the formation of B-cell aggregates after H. suis infection. Moreover, the expression of genes associated with the lymphoid follicle formation was also effectively suppressed by anti-CXCL13 antibody treatment. These results suggest that the upregulation of CXCL13 has an important role in the development of gastric MALT lymphomas and highlight the potential of anti-CXCL13 antibody for protection against Helicobacter-induced gastric diseases.

Helicobacter pylori infection and normal colorectal mucosa–adenomatous polyp–adenocarcinoma sequence: a meta‐analysis of 27 case–control studies

The study aimed to determine whether Helicobacter pylori infection is associated with colorectal adenocarcinoma and to quantify the extent of the risk. A literature search was performed to identify studies published between 1995 and 2012 for relevant risk estimates. Fixed and random effect meta-analytical techniques were conducted for colorectal adenocarcinoma and adenomatous polyp. Twenty-seven case-controlled studies involving 3450 adenocarcinoma patients, 1304 adenomatous polyp patients and more than 4000 controls were included. Helicobacter pylori was associated with an increased risk of colorectal adenocarcinoma and adenomatous polyp [odds ratio (OR) 1.24, 95% CI 1.12-1.37, P = 0.66; OR 1.87, 95% CI 1.53-2.28, P = 0.81]. There was a significant association between the CagA-positive strain and adenocarcinoma risk (OR 1.22, 95% CI 1.08-1.37, P = 0.05). In addition, there was an increased risk of tubular adenoma and villous adenoma formation (OR 3.06, 95% CI 1.98-4.73, P = 0.14; OR 2.05, 95% CI 0.84-4.97, P = 0.86). The meta-analysis suggests a promoting effect of Helicobacter pylori on the risk of adenocarcinoma. It also suggests that Helicobacter infection might have its influence at the start of the adenomatous polyp disease sequence.

Helicobacter pylori sensitizes TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in human gastric epithelial cells through regulation of FLIP

Helicobacter pylori (H. pylori) infection is associated with chronic gastritis, peptic ulcer and gastric cancer. Apoptosis induced by microbial infections is implicated in the pathogenesis of H. pylori infection. Here we show that human gastric epithelial cells sensitized to H. pylori confer susceptibility to TRAIL-mediated apoptosis via modulation of death receptor signaling. Human gastric epithelial cells are intrinsically resistant to TRAIL-mediated apoptosis. The induction of TRAIL sensitivity by H. pylori is dependent on the activation of caspase-8 and its downstream pathway. H. pylori induces caspase-8 activation via enhanced assembly of the TRAIL death-inducing signaling complex (DISC) through downregulation of cellular FLICE-inhibitory protein (FLIP). Overexpression of FLIP abolished the H. pylori-induced TRAIL sensitivity in human gastric epithelial cells. Our study thus demonstrates that H. pylori induces sensitivity to TRAIL apoptosis by regulation of FLIP and assembly of DISC, which initiates caspase activation, resulting in the breakdown of resistance to apoptosis, and provides insight into the pathogenesis of gastric damage in Helicobacter infection. Modulation of host apoptosis signaling by bacterial interaction adds a new dimension to the pathogenesis of Helicobacter.

Changing prevalence patterns in endoscopic and histological diagnosis of gastritis? Data from a cross-sectional Central European multicentre study

Traditionally, Helicobacter infection is considered to be the most common cause of gastritis. In the cross-sectional Central European histoGERD trial, we assessed the prevalence of different types of gastritis, correlating histological and endoscopic diagnoses. A total of 1123 individuals participated in an observational multicentre study. Endoscopists classified individuals as positive or negative for gastritis and rendered the putative cause. Pathologists evaluated biopsy specimens based upon the Updated Sydney System. Histological diagnosis of gastritis was made in 639 (56.9%) participants. In all, 210 (18.7%) individuals were diagnosed with Helicobacter gastritis, 215 (19.1%) with post Helicobacter gastritis, 234 (20.8%) with reactive gastropathy, 26 (2.3%) with autoimmune gastritis, and 6 (0.5%) with focally enhanced gastritis related to Crohn's disease. In 46 out of 639 (7.2%) individuals diagnosed with gastritis, combinations of different histological subtypes were noted the most common being reactive gastropathy and post Helicobacter gastritis. Endoscopic diagnosis of gastritis was made in 534 (47.6%) individuals. Reactive gastropathy was more common than active Helicobacter gastritis, and the majority of cases attributable to Helicobacter infection were no longer ongoing, i.e. post Helicobacter gastritis. Agreement between histological and endoscopic diagnoses was better in reactive gastropathy than in Helicobacter gastritis.

Mouse models of gastric carcinogenesis.

Gastric cancer is one of the most common cancers in the world. Animal models have been used to elucidate the details of the molecular mechanisms of various cancers. However, most inbred strains of mice have resistance to gastric carcinogenesis. Helicobacter infection and carcinogen treatment have been used to establish mouse models that exhibit phenotypes similar to those of human gastric cancer. A large number of transgenic and knockout mouse models of gastric cancer have been developed using genetic engineering. A combination of carcinogens and gene manipulation has been applied to facilitate development of advanced gastric cancer; however, it is rare for mouse models of gastric cancer to show aggressive, metastatic phenotypes required for preclinical studies. Here, we review current mouse models of gastric carcinogenesis and provide our perspectives on future developments in this field.

Capsaicin as new orally applicable gastroprotective and therapeutic drug alone or in combination with nonsteroidal anti-inflammatory drugs in healthy human subjects and in patients.

Capsaicin is a specific compound acting on capsaicin-sensitive afferent nerves. Capsaicin was used to study the different events of human gastrointestinal physiology, pathology, and clinical pharmacology, and possible therapeutic approaches to enhance gastrointestinal mucosal defense in healthy human subjects and in patients with various different gastrointestinal disorders as well as its use with nonsteroidal anti-inflammatory drugs (NSAIDs) in healthy subjects and in patients. The observations were carried out in 198 healthy human subjects and in 178 patients with different gastrointestinal (GI) diseases (gastritis, erosions, ulcer, polyps, cancer, inflammatory bowel diseases, colorectal polyps, cancers), and in 69 patients with chronic (Helicobacter pylori positive and negative) gastritis (before and after eradication treatment). The gastric secretory responses and their chemical composition, gastric emptying, sugar loading test, gastric transmucosal potential difference (GTPD) with application of capsaicin alone, after ethanol alone and with capsaicin, indomethacin-induced gastric mucosal microbleeding without and with capsaicin were studied. The immunohistochemical examinations of the capsaicin receptor (TRVP1), calcitonin gene- related peptide (CGRP), and substance P (SP) were carried out in gastrointestinal tract, and especially in patients with chronic gastritis (with and without Helicobacter infection, before and after classical eradication treatment). Classical molecular pharmacological methods were applied to study the drugs inhibiting the gastric basal acid output. Capsaicin decreased the gastric basal output, enhanced the "non-parietal" (buffering) component of gastric secretory responses, and gastric emptying, and the release of glucagon. Capsaicin prevented the indomethacin- and ethanol-induced gastric mucosal damage; meanwhile capsaicin itself enhanced (GTPD). Capsaicin prevented the indomethacin-induced gastric mucosal microbleeding. The expression of TRVP1 and CGRP increased in the gastric mucosa of patients with chronic gastritis (independently of the presence of Helicobacter pylori infection), and the successfully carried out eradication treatment. The human first phase examinations (the application of acetylsalicylic acid (ASA), diclqfenac, and naproxen together with capcaicinoids) (given in doses that stimulate capsaicin-sensitive afferent vagal nerves) showed no change in the pharmacokinetic parameters of ASA and diclofenac and the ASA and diclofenac-induced platelet aggregation. Capsaicin represents a new orally applicable gastroprotective agent in healthy human subjects and in patients with different chemical and Helicobacter pylori-induced mucosal damage and in many other diseases requiring treatment with NSAIDs.

Gastric pseudocarcinomatous regeneration

<h3>Introduction</h3> NSAID and ASA intake for various reasons is a widespread worldwide phenomenon. The first gastroscopic observation of ASA effects in the stomach dates back to 1938. Up till the beginning of the 1990s before the era of Helicobacter eradication 70% of all gastric ulcers were connected to Helicobacter infection. From the beginning of the 21st century almost 70% of gastric ulcers are now believed to be based on NSAID/ASA intake. NSAID damages the epithelium in three ways: a) direct damage by inhibition of prostaglandin, b) inducing complications in preexisting ulcers, c) enhanced bleeding (due to inhibition of platelet aggregation). Besides these systemic effects, topical effects may play a role in ulcer etiogenesis with entrapment of H+ ions within the cells by ion trapping. In conjunction with swelling of the cappilary endothelium these processes lead to the typical ischemic necrosis in NSAID ulcerations. It has been shown earlier that such typical necrosis may help to identify the etiology of gastric erosions and ulcerations. Regernating cells and ischemic damage may lead to hyperchromatic, pleomorphic cells that may sometimes be mixed up with carcinomatous changes. We aimed to answer the question how many gastric biopsies were erroneously assigned representing neoplastic changes instead of regenerative changes in cases that were sent in for second opinion. <h3>Patients and methods</h3> Within ten years 738 gastric biopsy cases with suspicion for neoplasia were sent in for second opinion. Among these 228 cases were downstaged to pseudoneoplastic regeneration, 489 clear cut gastric carcinomas and 19 cases were diagnosed as tubular adenoma (LGD). <h3>Results</h3> There were no gender differences in cases with regenerative changes (1.1:1) and adenomas (0.9:1) but carcinomas were more likely to be diagnosed in males (1.6:1). Patients with regernative changes significantly younger than carcinoma patients (62.8 vs 68.3 years). Regenerative lesions were found in 80% of the cases in the antrum whereas only 62% of the carcinomas occurred in the antrum. Following the time line from 2001 to 2011 it became evident that the overdiagnosis of regenerative changes as carcinomatous lesions decreased to 20% from the intial number in 2001. In parallel an increase in correct carcinoma diagnoses was observed. The gastritis status may help in a questionable situation since in regenerative changes less than 20% of the individuals had an active Helicobacter gastritis whereas this was in more than 70% the case in carcinoma patients. <h3>Discussion</h3> The diagnosis of pseudocarcinomatous regeneration is an important differential diagnosis of neoplastic gastric lesions. In some cases it can be really hard to distinguish bizarre epithelial changes due to drug incuded lesions from carcinomatous foci. Without Helicobacter gastritis the diagnosis of carcinoma should be made even more carefully and the differential diagnosis of pseudocarcinomatous changes should be considered. Fortunatly with time the number of erroneously carcinoma diagnoses went down in 2011 to 20% compared to the year 2001. Nevertheless gastric ulcerations should always receive proper follow-up with biopsies until healed. In difficult cases a second opinion by an experienced GI-pathologist may be helpful to confirm pseudocarcinomatous changes vs carcinomatous lesions.

Eradication of gastric Helicobacter spp. by triple therapy in dogs

The aim of this study was to determine the efficacy of a triple anti-Helicobacter therapy using omeprazole, amoxicillin and clarithromycin (OAC) in dogs. A total of 15 healthy adult stray dogs with naturally acquired Helicobacter infection were evaluated using polymerase chain reaction and rapid urease test. Subsequently, they received a 21-day triple regimen. One day after the discontinuation of treatment, a second molecular analysis of gastric biopsies revealed complete eradication of Helicobacter DNA with negative quantitative urease testing in all 15 dogs. Our results confirmed the high prevalence of gastric Helicobacter-like organisms (GHLOs) in the stray dog population of Shiraz, Iran, and the effectiveness of our therapeutic regimen for the complete eradication of these microorganisms in stray dogs. In conclusion, for the complete elimination of non-pylori Helicobacter spp. from the gastric mucosa of dogs, a 21-day three-drug regimen with omeprazole, amoxicillin and clarithromycin is suggested.

A Cross-Sectional Study of Helicobacter Infection Among Laboratory Animals and Animal Research Workers

A Cross-Sectional Study of Helicobacter Infection Among Laboratory Animals and Animal Research Workers

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

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.