Analysis of p53 gene mutations in Helicobacter pylori-associated gastritis mucosa in endoscopic biopsy specimens.

BACKGROUND: No previous report has shown the relationship between Helicobacter pylori infection and a direct sequence analysis of p53 gene mutation in a biopsy sample of human gastric mucosa. METHODS: A total of 60 endoscopic biopsies samples (21 patients with H. pylori-positive gastritis and 9 patients with H. pylori-negative gastritis), including antral mucosa and corpus mucosa, were used in this study. Direct DNA sequencing of exons 5, 6, 7, and 8 of the p53 gene was performed by the dyedeoxy terminator method. RESULTS: Mutations in the p53 gene were identified in non-hot spot codons in exon 7 and 8 in 11 of 21 samples (52.4%) from H. pylori-positive gastritis patients. There was no mutation in H. pylori-negative gastritis patients. CONCLUSIONS: This finding shows that H. pylori infection can induce p53 point mutations and appears to be involved in the pathway leading to dysplasia or carcinoma.     

Helicobacter pylori infection in patients with celiac disease

BACKGROUND AND AIMS: Patients with Helicobacter pylori gastritis are more likely to have increased duodenal intraepithelial lymphocytes (IEL); this can be reversed by H. pylori eradication. We hypothesized that: (1) H. pylori-infected celiac disease (CD) patients could have different clinicopathological features from noninfected subjects; and (2) the histopathological responses to a gluten-free diet could be different in H. pylori-infected and noninfected patients. METHODS: Duodenal and gastric biopsies obtained from 80 adults with histologically and serologically confirmed CD before and after 12-18 months of a gluten-free diet were retrospectively evaluated. Gastritis was classified and scored according to the Updated Sydney System; duodenal biopsies were classified using both the Marsh-Oberhuber and a simplified classification proposed by our group. RESULTS: At baseline, 30 patients had H. pylori infection and 50 did not; at follow-up five new infections were detected. Fifteen patients (3 H. pylori-positive and 12 negative) had lymphocytic gastritis. At baseline, a greater proportion of H. pylori-negative patients had severe villous atrophy (p < 0.01), but milder forms were more prevalent in H. pylori-positive patients (p < 0.01). After a gluten-free diet, significant improvement occurred in all duodenal features (p < 0.001), irrespective of H. pylori status; gastric variables did not change, except for lymphocytic, which resolved in 2 infected and 10 noninfected patients. CONCLUSIONS: The clinical features of CD patients are unrelated to H. pylori gastritis, and a gluten-free diet is equally effective in infected as in uninfected patients. The higher prevalence of milder duodenal lesions in CD patients with H. pylori infection suggests that lymphocytosis induced by H. pylori gastric infection becomes less obvious as profound inflammatory and structural changes alter the mucosal architecture. This study also provides further support for a pathogenetic relationship between CD and lymphocytic gastritis.     

Helicobacter pylori in gastric corpus of patients 20 years after partial gastric resection

AIM: To determine the long-term prevalence of Helicobacter pylori (H pylori) gastritis in patients after partial gastric resection due to peptic ulcer, and to compare the severity of H pylori-positive gastritis in the corpus mucosa between partial gastrectomy patients and matched controls. METHODS: Endoscopic biopsies were obtained from 57 patients after partial gastric resection for histological examination using hematoxylin/eosin and Warthin-Starry staining. Gastritis was graded according to the updated Sydney system. Severity of corpus gastritis was compared between H pylori-positive partial gastrectomy patients and H pylori-positive duodenal ulcer patients matched for age and gender. RESULTS: In partial gastrectomy patients, surgery was performed 20 years (median) prior to evaluation. In 25 patients (43.8%) H pylori was detected histologically in the gastric remnant. Gastric atrophy was more common in H pylori-positive compared to H pylori-negative partial gastrectomy patients (P<0.05). The severity of corpus gastritis was significantly lower in H pylori-positive partial gastrectomy patients compared to duodenal ulcer patients (P<0.01). There were no significant differences in the activity of gastritis, atrophy and intestinal metaplasia between the two groups. CONCLUSION: The long-term prevalence of H pylori gastritis in the gastric corpus of patients who underwent partial gastric resection due to peptic ulcer disease is comparable to the general population. The expression of H pylori gastritis in the gastric remnant does not resemble the gastric cancer phenotype.     

Campylobacter pylori: Associations with Antral and Fundic Mucosal Histology and Diagnosis by Serology in Patients with Upper Gastrointestinal Symptoms

We obtained a sample of serum and mucosal biopsies from the antrum and usually from the corpus of the stomach from 35 symptomatic patients during routine endoscopy to analyze for the relationship between Campylobacter pylori infection, inflammation, and the diagnostic utility of a C. pylori IgG antibody assay. C. pylori was identified prospectively by culture and/or silver stain in gastric biopsies from 24 patients, and the antibody was detected in 19 (79%) of these patients. The antibody assay was positive in three other patients, two of whom had C. pylori, on reexamination of their biopsies. The accuracy of the antibody assay was 83%. Inflammation was detected in all C. pylori-positive antral biopsies (N = 19). However, five (71%) of seven antral biopsies from patients in whom all tests were C. pylori negative, also had inflammation, constituting 17% of all patients with antral gastritis (N = 30). Both antral and fundic mucosa were obtained from 26 patients and, in this group, C. pylori was detected in fundic mucosa from all patients in whom the organism also was present in the antrum (N = 15). In significant (p less than 0.001) contrast to C. pylori-positive antral histology, fundic mucosal histology was normal in 6 (40%) of 15 C. pylori-positive biopsies, all from patients with peptic ulcer disease. We conclude that C. pylori antibody assays will be useful for epidemiological studies and initial screening of the C. pylori status of individual patients. In addition, there is a high concordance rate between antral and fundic mucosa for the prevalence of C. pylori, but in contrast to the probable etiological role of C. pylori in antral gastritis, the organism appears to be only a commensal of fundic mucosa. Moreover, C. pylori infection is not evident in all patients with type B gastritis.     

Helicobacter pylori infection affects the expression of PCNA, p53, c-erbB-2 and Bcl-2 in the human gastric mucosa.

OBJECTIVE: Helicobacter pylori infection has been related to gastric carcinogenesis. This association is based on epidemiological data, pathological changes observed in the gastric mucosa, and chemical products from bacteria that may induce damage of DNA. In the present study we examined gastric endoscopic biopsies from patients with chronic gastritis, with and without H. pylori infection, and surgical biopsies from gastric cancer patients to evaluate whether this bacteria may induce changes in the expression of molecular markers associated with carcinogenesis. PATIENTS AND METHODS: the study involved 57 biopsies from the antral region of the stomach of patients with chronic gastritis and gastric cancer that were analyzed by immunohistochemistry. Molecular markers examined were: PCNA (Proliferating Cell Nuclear Antigen), p53, c-erbB-2, Bcl-2, and p21 H-ras. RESULTS: PCNA content of epithelial cells was significantly higher in H. pylori infected biopsies. Treatment aimed to eradicate H. pylori decreased the level of PCNA-positive cells in the group of patients that became H. pylori-negative as well as in H. pylori-positive patients. Nuclear p53 expression (used here as a surrogate marker for p53 mutation/inactivation) and c-erbB-2 expression were observed only in the group of patients that remained with the bacteria after treatment. A higher bcl-2 expression in lymphoid cells was observed in H. pylori-positive biopsies, and treatment did not change the expression of this protein. No significant expression of p21 H-ras was observed in the studied biopsies. CONCLUSION: this study suggests that H. pylori is involved in the induction of molecular changes that might predispose human gastric mucosa cells to pre-neoplastic and neoplastic events.     

Helicobacter pylori induces apoptosis in mucosal lymphocytes in patients with gastritis

BACKGROUND: Previous studies suggest that Helicobacter pylori (H. pylori) induces apoptosis and compensatory hyperproliferation in gastric epithelial cells possibly explaining the carcinogenic capacity of the bacteria. The aim of this study was to measure the effect of H. pylori on apoptosis of gastric lymphoid cells in view of the development of gastric lymphoma. METHODS: 16 H. pylori-positive and 19 H. pylori-negative individuals were enrolled. Single cell suspensions were prepared from antral biopsies and apoptosis was measured by staining with the TUNEL-assay and the fluorochrome Hoechst 33342. Lymphocyte subsets were simultaneously identified by immunocytochemistry. RESULTS: The apoptotic index of all gastric mucosal cells was significantly higher in H. pylori-positive mucosa compared to negative controls. Additionally, H. pylori-infected patients showed a significant increase in apoptosis of mucosal B-lymphocytes. Apoptosis of T cells and plasma cells was unaffected by H. pylori. CONCLUSION: H. pylori induces apoptosis in mucosal B cells which might be important in the development of gastritis and possibly B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT).     

Interaction between Helicobacter pylori infection and untreated coeliac disease on gastric histological pattern

OBJECTIVE: Helicobacter pylori infection is the major agent of gastric damage. Coeliac disease may affect the morphology and function of the entire gastrointestinal tract from the stomach to the colon. The aim of this study was to assess the gastric histological pattern in patients with H. pylori and untreated coeliac disease. MATERIAL AND METHODS: We retrospectively enrolled 183 H. pylori-positive patients with (85, group A) and without (98, group B) untreated coeliac disease. The groups were similar for age, gender and smoking habit, and all the patients came from the same geographical area. Histological evaluation of gastric pattern was performed on 4 biopsies (2 in the antrum, 2 in the corpus). Gastric damage was classified according to the modified Sydney System. Diagnosis of H. pylori infection was based on positivity to histology. The chi-square test was used to assess differences between groups. A p-value <0.05 was considered significant. RESULTS: Group A showed a significantly higher prevalence of follicular gastritis than group B (23.5% versus 12.2%, p=0.045). A significantly lower prevalence of atrophic gastritis was observed in group A compared with that in group B (6% versus 22.5%, p=0.002). The prevalence of chronic superficial gastritis, activity degree and intestinal metaplasia was similar between the two groups. CONCLUSIONS: In patients with H. pylori infection, untreated coeliac disease could represent a risk factor for follicular gastritis and is associated with a lower prevalence of atrophic gastritis. The complex interaction between H. pylori and untreated coeliac disease on Th-1/Th-2 balance in the gastric mucosa could explain these results.     

Relationship of Helicobacter pylori-associated Gastritis and Polymorphonuclear Leukocyte Elastase

Abstract: Background: Much remains to be clarified about the mechanisms of Helicobacter pylori (H. pylori)-associated gastritis. We considered the possibility of neutrophil involvement and investigated the role of polymorphonuclear leukocyte elastase (PMN-E) in the etiology of H. pylori-associated gastritis. Methods: In 60 patients with gastritis, infection by H. pylori was diagnosed by a combination of the ELISA method and conventional culture method. The hexosamine contents of the mucosal tissues and plasma polymorphonucler leukocyte elastase complexes (PMN-EC) were determined. Results: PMN-EC was found to be elevated in H. pylori-positive gastritis patients, and the degree of elevation was proportionately related to the grade of gastritis inflammation. The hexosamine concentration of the gastric antral mucosa was significantly lower in H. pylori-positive patients than in the H. pylori-negative patients. The ratio of PMN-EC/gastric mucosal hexosamine concentration was significantly higher in the H. pylori-positive group than in the negative group. Conclusion: These data suggest that one of the mechanisms of the H. pylori-associated gastritis may be the infiltration of neutrophils into the gastric mucosa followed by the release of PMN-E which is responsible for the degradation of gastric mucosal proteins and resultant tissue damages.     

Mucosal tumour necrosis factor alpha and interleukin-6 in patients with Helicobacter pylori associated gastritis.

The production of tumour necrosis factor alpha (TNF alpha) and interleukin-6 by human antral mucosa during short term culture in vitro has been measured by enzyme linked immunosorbent assay. TNF alpha and interleukin-6 concentrations in culture supernatants were significantly greater (p less than 0.001) in patients infected with Helicobacter pylori, all of whom had chronic gastritis, than in patients who were H pylori negative with histologically normal gastric mucosa. Among H pylori colonised patients, TNF alpha concentrations were significantly higher in those with active gastritis and neutrophil infiltration into the epithelium than in those with inactive gastritis. In contrast, interleukin-6 concentrations were raised in both active and inactive gastritis. This study shows that H pylori gastritis is associated with increased gastric mucosal production of TNF alpha and interleukin-6 and that the nature of the mucosal cytokine response varies with the immunohistology of the disease. Inflammatory cytokines generated locally within the gastric mucosa could be relevant to the gastric physiology of H pylori infection.     

Helicobacter pyloriin gastric corpus of patients 20 years after partial gastric resection

AIM:To determine the long-term prevalence of Helicobacterpylori(H pylori)gastritis in patients after partial gastricresection due to peptic ulcer,and to compare the severityof Hpylori-positive gastritis in the corpus mucosa betweenpartial gastrectomy patients and matched controls.METHODS:Endoscopic biopsies were obtained from 57patients after partial gastric resection for histologicalexamination using hematoxylin/eosin and Warthin-Starrystaining.Gastritis was graded according to the updatedSydney system.Severity of corpus gastritis was comparedbetween Hpylori-positive partial gastrectomy patients andHpylori-positive duodenal ulcer patients matched for ageand gender.RESULTS:In partial gastrectomy patients,surgery wasperformed 20 years(median)prior to evaluation.In 25patients(43.8%)Hpyloriwas detected histologically inthe gastric remnant.Gastric atrophy was more common inH pylori-positive compared to H pylori-negative partialgastrectomy patients(P<0.05).The severity of corpusgastritis was significantly lower in Hpylori-positive partialgastrectomy patients compared to duodenal ulcer patients(P<0.01).There were no significant differences in theactivity of gastritis,atrophy and intestinal metaplasiabetween the two groups.CONCLUSION:The long-term prevalence of Hpylorigastritisin the gastric corpus of patients who underwent partialgastric resection due to peptic ulcer disease is comparableto the general population.The expression of Hpylorigastritisin the gastric remnant does not resemble the gastric cancerphenotype.     

Helicobacter pylori, smoking and gastroduodenitis.

There is epidemiological evidence of an association between cigarette smoking and gastritis. To find out whether the reason for this might be related to the presence of Helicobacter pylori, biopsies were taken from the gastric corpus and antrum and from the duodenal bulb in 106 consecutive patients referred for oesophagogastroduodenoscopy because of epigastric pain. Patients with ulcer disease or cancer were excluded. The biopsy specimens were cultured for H. pylori and examined histologically for the presence and grade of gastritis and duodenitis. Thirty-five percent of the patients were H. pylori-positive and 57% had histological gastritis; 37% were cigarette smokers and among these, H. pylori was found significantly less frequently than in non-smokers (18 and 45%, respectively; 2p = 0.0083). Among patients colonized with H. pylori, gastritis was found in 89% compared to 39% in non-colonized patients (2p less than 0.0001). In spite of this, 51% of the smokers and 60% of the non-smokers (2p = 0.85) had histological gastritic mucosa. No differences in the severity of the gastritis or the duodenitis in patients with histologically positive findings could be seen when comparing smokers to non-smokers and H. pylori-positive to H. pylori-negative patients.     

Helicobacter pylori infection and chronic immune thrombocytopenic purpura: long-term results of bacterium eradication and association with bacterium virulence profiles

Eradication of Helicobacter pylori may lead to improvement of chronic immune thrombocytopenic purpura (ITP), although its efficacy over time is uncertain. We report the results of H pylori screening and eradication in 75 consecutive adult patients with ITP. We also used molecular methods to investigate lymphocyte clonality and H pylori genotypes in the gastric biopsies from 10 H pylori-positive patients with ITP and 19 H pylori-positive patients without ITP with chronic gastritis. Active H pylori infection was documented in 38 (51%) patients and successfully eradicated in 34 (89%) patients. After a median follow-up of 60 months, a persistent platelet response in 23 (68%) of patients with eradicated infection was observed; 1 relapse occurred. No differences in mucosal B- or T-cell clonalities were observed between patients with ITP and control participants. Of note, the frequency of the H pylori cagA gene (P = .02) and the frequency of concomitant H pylori cagA, vacAs1, and iceA genes (triple-positive strains; P = .015) resulted statistically higher in patients with ITP than in control participants. All asymptomatic H pylori-positive patients with ITP were suffering from chronic gastritis. Our data suggest a sustained platelet recovery in a proportion of patients with ITP by H pylori eradication alone. Overrepresentation of specific H pylori genotypes in ITP suggests a possible role for bacterium-related factors in the disease pathogenesis.     

Mucosal peptic activity during Helicobacter pylori infection in pediatric patients.

Intramucosal peptic activity may participate in the genesis of acute and chronic superficial gastritis. The proteolytic activity of homogenates of gastric mucosa (antrum and body) and duodenum were measured at pH 2.0 (total peptic activity) after exposure to pH 8.0 (pepsinogen) and the activated pepsinogen (pepsin) was calculated in pediatric patients investigated for the presence of Helicobacter pylori (H pylori), 122 antral, 77 stomach body, and 74 duodenal biopsies were examined in 43 H pylori positive patients, 51 controls, and 28 H pylori negative gastritis patients. Activated pepsinogen was significantly reduced in the stomach of H pylori positive patients only. Pepsinogen values were similar in all the anatomical areas tested in all patients. In 13 H pylori positive patients reinvestigated three months after antibiotic therapy, antral mucosal activated pepsinogen activity increased significantly (mean pretreatment 1.56 (1.0) U/mg protein versus mean post-treatment 2.72 (1.7) U/mg protein) and reached values comparable with controls. The decreased activated pepsinogen activity in association with normal pepsinogen content observed in the antrum of H pylori positive gastritis patients indicate local pepsin inactivation or alternately enhanced removal into the gastric lumen or backflow into the circulation.     

Effect of acid-suppressive therapy on Helicobacter pylori production of interleukin-8 in the gastric mucosa.

BACKGROUND: Recent studies have shown that acid-suppressive therapy increases the severity of Helicobacter pylori- associated gastritis in the corpus. PURPOSE: To evaluate interleukin (IL)-8 production in the gastric corpus mucosa before and during acid-suppressive therapy in H pylori-infected patients. PATIENTS AND METHODS: Ten patients with reflux esophagitis (five H pylori-positive and five H pylori-negative) were treated with omeprazole 20 mg. Serum gastrin concentrations, H pylori colonization density and mucosal IL-8 levels in the corpus were investigated at entry and two weeks after starting therapy. IL-8 levels were measured by ELISA. The organism density was determined, and scored according to area occupied by the bacterial colonies. The presence of H pylori was assessed by rapid urease testing and histological finding of gastric biopsy specimens. RESULTS: In H pylori-positive patients, concentrations of IL-8 during therapy significantly exceeded those before therapy (36.2+/-6. 8 versus 18.3+/-3.8 pg/mg protein; P<0.05) without altering H pylori density. In H pylori-negative patients, IL-8 levels were similar before and during therapy (6.1+/-2.7 versus 6.3+/-3.0 pg/mg protein). Concentrations of gastrin during therapy were significantly higher than those before therapy in all patients. CONCLUSIONS: The results suggest that acid suppression increases mucosal IL-8 levels in H pylori-infected patients with reflux esophagitis.     

Evolution of gastritis in patients with gastric erosions

OBJECTIVE: Gastric erosions are mainly associated with Helicobacter pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs), but there has been no information available on the long-term evolution of gastritis in subjects with erosions. MATERIAL AND METHODS: A series of 117 patients with gastric erosions without peptic ulcer disease and matched controls without erosions or ulcers were studied. Available subjects underwent endoscopy and biopsy 17 years later. Parietal cell antibodies were analysed at the first visit. RESULTS: Fifty-two patients and 67 controls were available for follow-up. Since H. pylori was a major determinant of gastritis, only subjects with unchanged H. pylori status were included in the evaluation of gastritis progression. At the follow-up visit, gastric erosions were present in 38% (16/42) of the patients and 11% (5/46) of the controls (p=0.005). In H. pylori-negative subjects, no evolution of histological changes was seen. In H. pylori-positive subjects, body gastritis was initially less active in the erosion group. With time, antral gastritis worsened only in the erosion group. Parietal cell antibodies were more common in the control group (23%; erosion patients 0%; p=0.01), which also showed worsening of gastritis (p=0.003) and aggravation of atrophy (p=0.002) in the body mucosa. CONCLUSIONS: Gastritis in H. pylori-positive subjects with gastric erosions shows evolution of antral predominance, body predominance including development of atrophic changes being rare. Accordingly, patients with erosions share the characteristics of gastritis of the duodenal ulcer phenotype. These findings support the importance of H. pylori and acid in the pathogenesis of gastric erosions in H. pylori-positive patients.     

Increase in apoptosis and decrease in ornithine decarboxylase activity of the gastric mucosa in patients with atrophic gastritis and gastric ulcer after successful eradication of Helicobacter pylori

OBJECTIVE: Recent reports have shown that patients infected with Helicobacter pylori (H. pylori) have a higher risk of gastric cancer. However, the mechanism of this increased risk is still unclear. In the gastric mucosa, the size of a continuously renewed population of cells is determined by the rates of cell production and of cell loss. Ornithine decarboxylase (ODC) activity is elevated in various gastrointestinal cancers and serves as a marker of mucosal proliferative activity. Apoptosis occurs throughout the gut and is associated with cell loss. Both cell proliferation and cell loss have important roles in H. pylori-associated gastric carcinogenesis. Therefore, we investigated the effect of H. pylori eradication on ODC activity and apoptosis in the gastric mucosa of patients with atrophic gastritis and gastric ulcers. METHODS: Biopsy specimens of the gastric antrum were obtained at endoscopy from 17 H. pylori-positive gastric ulcers patients and 15 H. pylori-positive gastritis patients before and 4 wk after eradication therapy with amoxicillin, omeprazole, and a new anti-ulcer agent, ecabet sodium, and from 10 gastric ulcer patients in whom ulcer healed but H. pylori was left untreated. ODC activity and induction of apoptosis were determined immunohistochemically. RESULTS: H. pylori was successfully eradicated with the triple therapy in 12 (80%) of 15 gastritis patients and 13 (76%) of 17 gastric ulcer patients. ODC activity was present in the gastric mucosa in 21 (84%) patients before eradication but in only four (16%) patients after successful eradication (p = 0.0005). The apoptotic index increased significantly (p = 0.0006) from 4.2% +/- 0.4% before treatment to 7.4% +/- 0.5% after successful eradication. CONCLUSIONS: Successful eradication of H. pylori decreases mucosal ODC activity and increases apoptosis in the gastric mucosa. These findings indicate that by decreasing mucosal cell proliferation and increasing epithelial cell loss, H. pylori eradication may help decrease the subsequent risk of gastric cancer.     

Characteristics of gastritis in patients with Helicobacter pylori-positive reflux esophagitis

BACKGROUND AND AIM: The influence of Helicobacter pylori on gastric acid secretion differs with the status of gastritis. The histological characteristics of gastritis in H. pylori-positive patients with reflux esophagitis have not been fully investigated. We therefore studied the pattern of endoscopic gastric mucosal atrophy and degree of histological gastritis in such patients. METHODS: Subjects comprised 41 H. pylori-positive patients with reflux esophagitis, 41 age- and sex-matched patients with duodenal ulcer, and 41 patients with early gastric cancer. The endoscopic pattern of gastric mucosal atrophy was reviewed, and the degree of histological gastritis in biopsy specimens from the antrum and corpus was assessed in accordance with the updated Sydney system. RESULTS: The grade of endoscopic and histological gastric mucosal atrophy in patients with reflux esophagitis was significantly lower than that in patients with gastric cancer, and the histological scores for antral atrophy and metaplasia in patients with reflux esophagitis tended to be lower than those in patients with duodenal ulcer. In patients with reflux esophagitis and duodenal ulcer, the scores for antral inflammation and activity tended to be higher than those for the corpus. Conversely, the inflammation and activity score in patients with early gastric cancer showed a corpus-predominant gastritis pattern. CONCLUSION: In H. pylori-positive patients with reflux esophagitis, the degree of endoscopic gastric mucosal atrophy is low and histologically there is an antral-predominant gastritis pattern. Therefore, gastric acid secretion in H. pylori-positive patients with reflux esophagitis may be augmented by H. pylori infection.     

Prolonged use of proton pump inhibitors, CagA status, and the outcome of Helicobacter pylori gastritis

GOALS AND BACKGROUND: To assess whether prolonged use of proton pump inhibitors (PPIs) in patients infected with Helicobacter pylori has adverse effects on gastritis. STUDY: We studied 34 H. pylori-positive individuals with reflux esophagitis, Barrett esophagus, or nonulcer dyspepsia. Half of them were on maintenance treatment with PPIs (mean, 8 years) and half were not.H. pylori and CagA status were tested serologically. Gastric biopsies were classified histopathologically by the updated Sydney classification. RESULTS: Proton pump inhibitors in H. pylori gastritis are associated with significantly less antral inflammation and lower H. pylori density, regardless of CagA status. There was a tendency toward more antral atrophy in patients with the CagA strain who were undergoing maintenance treatment with PPIs (p = 0.08), but there was an opposite tendency in CagA-negative individuals (p = 0.08). Intestinal metaplasia was seen more frequently in CagA-positive, treated individuals (p = 0.028). CONCLUSIONS: These findings support the hypothesis that CagA status is important in the progression to atrophy and that maintenance treatment with PPIs accelerate this progression, while reducing inflammatory infiltration.     

Expression of cytokeratins in Helicobacter pylori -associated chronic gastritis of adult patients infected with cagA ＋ strains： An immunohistochemical study

AIM:To investigate the expression of differentcytokeratins(CKs)in gastric epithelium of adult patientswith chronic gastritis infected with Helicobacter pylori(Hpylori)cagA strains.METHODS:The expression of CK 7,8,18,19 and 20was studied immunohistochemically in antral gastricbiopsies of 84 patients.All the CKs were immunostainedin cagA H pylori gastritis(57 cases),non-H pylori gastritis(17 cases)and normal gastric mucosa(10 cases).RESULTS:In cagA H pylori gastritis,CK8 wasexpressed comparably to the normal antral mucosafrom surface epithelium to deep glands.Distributionof CK18 and CK 19 was unchanged,i.e.transmucosal,but intensity of the expression was different in foveolarregion in comparison to normal gastric mucosa.Cytokeratin 18 immunoreactivity was significantly higherin the foveolar epithelium of H pylori-positive gastritiscompared to both Hpylori-negative gastritis and controls.On the contrary,decrease in CK19 immunoreactivityoccurred in foveolar epithelium of H pylori-positive gastritis.In both normal and inflamed antral mucosawithout Hpylori infection,CK20 was expressed strongly/moderately and homogenously in surface epithelium andupper foveolar region,but in H pylori-induced gastritissignificant decrease of expression in foveolar regionwas noted.Generally,in both normal antral mucosa andH pylori-negative gastritis,expression of CK7 was notobserved,while in about half cagA H pylori-infectedpatients,moderate focal CK7 immunoreactivity of theneck and coiled gland areas was registered,especially inareas with more severe inflammatory infiltrate.CONCLUSION:Alterations in expression of CK 7,18,19 and 20 together with normal expression of CK8 occurin antral mucosa of H pylori-associated chronic gastritisin adult patients infected with cagA strains.Alterationsin different cytokeratins expression might contribute toweakening of epithelial tight junctions observed in Hpylori-infected gastric mucosa.