Helicobacter pylori associated gastric diseases and lymphoid tissue hyperplasia in gastric antral mucosa

AIM: To investigate the relation between Helicobacter pylori associated gastroduodenal diseases and lymphoid tissue hyperplasia in the antral mucosa and to pursue its evolution after eradication of H pylori. METHODS: Gastric antral biopsy specimens were obtained from 438 patients with H pylori positive gastroduodenal diseases (185 chronic gastritis, 69 gastric ulcer, and 184 duodenal ulcer) and 50 H pylori negative healthy controls. Lymphoid follicles and aggregates were counted and other pathological features were scored according to the updated Sydney system for classification of chronic gastritis. After a course of anti-H pylori treatment, biopsy specimens were obtained at four to six weeks, 12 months, and 24 months in the chronic gastritis patient group. RESULTS: The total prevalence of lymphoid follicles and aggregates in the biopsies was 79.9% (350 of 438; 95% confidence intervals (CI), 0.76 to 0.84). The prevalence and density of lymphoid follicles and aggregates were significantly different in the various gastroduodenal diseases. The highest prevalence (89.9%; 95% CI, 0.83 to 0.97) and density (0.82) of lymphoid follicles and aggregates occurred in patients with gastric ulcers. The lowest prevalence of lymphoid follicles and aggregates was found in patients with chronic gastritis (74.6%; 95% CI, 0.68 to 0.81), and the lowest density of lymphoid follicles and aggregates (0.56) was seen in patients with duodenal ulcers. The prevalence and density of lymphoid follicles and aggregates correlated strongly with the activity and severity of gastric antral mucosal inflammation. The eradication of H pylori resulted in a decrease in the prevalence and density of lymphoid follicles and aggregates. CONCLUSION: The prevalence and density of lymphoid follicles and aggregates in gastric antral mucosal biopsies correlated closely with H pylori infection.     

The role of apoptosis and proliferation of epitheliocytes in morphogenesis of Helicobacter pylori-associated gastritis

77 patients with chronic Helicobacter gastritis verified endoscopically and exacerbation of duodenal ulcer were examined. H. pylori infection was identified by the rapid ureasa test (CLO-test) and Giemza staining. The patients received 7-day three-component therapy for eradication of H. pylori. Apoptosis and proliferation were studied in 16 patients in serial sections with the use of monoclonal antibodies. Eradication of H. pylori resulted in relief of inflammation and transformation of active gastritis in inactive one. H. pylori-associated gastritis is associated with activation of apoptosis of gastric mucosa epithelial cells and epitheliocytes proliferation. H. pylori eradication alters correlation between apoptosis of epitheliocytes and their proliferation: successful eradication of the infection decreases apoptosis, high proliferative activity of epitheliocytes persists reflecting enhancement of regeneration in gastric mucosa.     

Interobserver agreement in the assessment of gastritis reversibility after Helicobacter pylori eradication

AIM: Our aim was to determine interobserver agreement in the application of the Sydney system to assess reversibility of gastritis after Helicobacter pylori eradication. METHODS AND RESULTS: Forty-three patients with a Helicobacter pylori-positive duodenal ulcer disease were included in the study. All patients included had successful H. pylori eradication after different antimicrobial drug combinations. Biopsy samples were collected from antrum and body, according to the Sydney recommendations, before antimicrobial therapy, 2 months after and at yearly intervals during 2-4 years of follow up. Three pathologists, who were blind to clinical data, evaluated histological changes in 221 antral and 219 body specimens stained with haematoxylin and eosin and with Warthin Starry. The percentage of pairwise agreement, kappa and weighted kappa statistic were used. Agreement in recognizing the presence of H. pylori colonization of the gastric mucosa, activity of inflammation and intestinal metaplasia was over 90%. Agreement in recognizing chronic inflammation in the body and atrophy in the antrum was between 78 and 89% respectively. The kappa values were excellent (more than 0.75) for the grade of H. pylori in the body, good (between 0.50 and 0.75) for the grade of H. pylori in the antrum, grade of inflammatory activity and intestinal metaplasia in the antrum and moderate to good (0.38-0.53) for the grade of chronic inflammation. Kappa values were poor to good (from 0.17 to 0.57) only in evaluation of the grade of atrophy. CONCLUSION: Interobserver agreement in the application of the Sydney system to reversibility of gastritis after H. pylori was good. More strict criteria should be used for atrophy and to differentiate normal and mild chronic inflammation.     

Alterations in antral cytokine gene expression in peptic ulcer patients during ulcer healing and after Helicobacter pylori eradication

Earlier studies have shown that the antral immune response in Helicobacter pylori infection has a mixed Th1-Th2-T- regulatory profile. After eradication, a chronic inflammation remains in some patients, but a follow-up study with a comprehensive cytokine profile in has not previously been published. Twelve patients with H. pylori positive peptic ulcer disease (five antral and seven duodenal) were enrolled and cytokine gene expressions in antral biopsies were determined (1) at entry, (2) after resolving the ulcer with proton pump inhibitor (PPI) treatment and (3) after eradication. The second endoscopy was performed 4 weeks after ending the PPI treatment, and the third endoscopy was performed after a mean of 10 months after eradication. Inflammation was graded according to the updated Sydney system. Interleukin (IL)1β, IL8, IL12A, IL18, TNFα, IFNγ, IL4, IL6 and IL10 expression levels were analysed by real-time RT-PCR. Mixed mononuclear and neutrophil infiltrates were seen at entry and after ulcer healing. After eradication, low-grade mononuclear infiltrates were found. The cytokine expression levels after ulcer healing ( H. pylori positive gastritis) were not significantly different from the levels at entry (ulcer). After eradication, attenuation of the Th1 cytokines except for TNFα and a persisting increase of IL4 levels were observed, whereas the IL10 expression was markedly reduced. The present data did not indicate a specific ulcer promoting cytokine gene regulation profile. However, after eradication a chronic low-grade inflammation was seen with reduced Th1, prolonged Th2 and disappearance of the T- regulatory response.     

Improvement of gastric inflammation and resolution of epithelial damage one year after eradication of Helicobacter pylori.

AIMS--To investigate the effect of eradication of Helicobacter pylori infection on gastric epithelial damage and gastritis, scored according to the Sydney system. METHODS--Gastritis scores and epithelial damage were assessed in gastric biopsy specimens before, and five weeks and one year after anti-H pylori therapy in 66 patients with H pylori related gastritis. RESULTS--The mean initial levels of activity, inflammation, atrophy, intestinal metaplasia, and H pylori scores were higher in the antrum than in the corpus or fundus. Eradication of H pylori resulted in an improvement in the mean inflammatory score in antral biopsy specimens from 2.23 before treatment to 1.32 and 1.06, respectively, five weeks and one year after treatment. Corresponding values for fundic biopsy specimens were 1.30, 0.36 and 0.35. Activity scores improved from 1.41 before treatment to 0.13 and zero, respectively, five weeks and one year after treatment in antral biopsy specimens and from 0.60 before treatment to zero in fundic biopsy specimens. Before treatment, epithelial damage was present in 51% of biopsy specimens taken from the antrum and 23% of those from the corpus. Five weeks after eradication of H pylori none of the biopsy specimens revealed evidence of epithelial damage. CONCLUSION--Eradication of H pylori is followed by a rapid, significant improvement in the gastritis score and resolution of epithelial damage in antral and fundic mucosa.     

The comparison of histologic gastritis in patients with duodenal ulcer, chronic gastritis, gastric ulcer and gastric cancer

This study was designed to investigate the differences of histologic gastritis according to the endoscopic diagnosis, and between H. pylori positive and negative gastritis, using the Sydney system. A total of 122 patients (42 duodenal ulcer, 31 chronic gastritis, 35 gastric ulcer and 14 gastric cancer) underwent endoscopy with biopsies from the antrum and body. Among the 122 patients, 104 (85%) were H. pylori positive. H. pylori density of the antrum was significantly higher in duodenal ulcer than in chronic gastritis, gastric ulcer, and gastric cancer. The positivity of intestinal metaplasia was lowest in duodenal ulcer and highest in gastric cancer. H. pylori density as well as grade of activity, inflammation and atrophy were significantly higher in the antrum than in the body in duodenal ulcer, while in chronic gastritis, gastric ulcer and gastric cancer there was no difference of H. pylori density, activity, inflammation and atrophy between the antrum and body. The grade of activity and chronic inflammation were significantly higher in H. pylori positive patients than in H. pylori negative patients in both the antrum and body. In conclusion, the gastritis of duodenal ulcer was mainly localized to the antrum, while the gastritis of chronic gastritis, gastric ulcer or gastric cancer was rather uniform in the antrum and body. H. pylori seemed to be related to the development of chronic inflammation and activity.     

Time course of gastric mucosal changes in the assessment of long-term results of Helicobacter pylori eradication

The impact of Helicobacter pylori (H. pylori) eradication on the gastric mucosa (GM) was studied in patients with gastroduodenal ulcers. Clinical and morphological changes in the GM were assessed in 122 patients 3-7 years (mean 4.4 +/- 1.3 years) after eradication therapy and in 12 patients who had undergone H. pylori eradication. Successful H. pylori eradication in the gastric antral and body mucosa reduced inflammation, the degree of chronic inflammation, the number of lymphoid follicles, and the magnitude of gland atrophy. There were no statistically significant changes in intestinal metaplasia. The patients who had not received eradication therapy showed no significant GM changes as compared to the baseline values. In the unsuccessful eradication group, inflammation statistically significantly diminished in the gastric antrum and body with a reduction in the density of H. pylori contamination.     

Mast cells in Helicobacter pylori associated antral gastritis

Mast cells are known to be effector cells in various inflammatory reactions, but their role in gastritis is unclear. The present study was undertaken to investigate the extent of mast cell involvement in antral gastritis with and without Helicobacter pylori (H. pylori) infection and thus evaluate the possible role of mast cells in the pathogenesis of H. pylori-associated gastritis. Antral mucosal biopsies were taken from 212 subjects with symptoms suggestive of acid peptic disease. Sections were assessed for inflammation. Modified Giemsa stain was used to detect H. pylori infection and 1% toluidine blue to count mast cells. Mast cell counts were significantly higher in the antral mucosa even in H. pylori-negative gastritis (68.4 +/- 6.7/mm2), as compared to normal non-inflamed mucosa (45.7 +/- 5.8/mm2) (P < 0.05). However, with H. pylori infection, the mucosal mast cell count were markedly increased (123.8 +/- 4.7/mm2) as compared to normal mucosa (P < 0.01). and H. pylori-negative gastritis (P < 0.01) this increase was noticed uniformly in patients with H. pylori-positivity, irrespective of the presence or absence of a peptic ulcer. After cure of H. pylori infection, the mast cell density decreased significantly (44.9 +/- 4.6/mm2) to reach levels that were similar to those in normal mucosa. There was a positive correlation between the antral mucosal mast cell density and polymorphonuclear and mononuclear cell infiltration (rs = 0.61). H. pylori infection, and 0.73 respy. It was concluded that could be responsible for increasing the mast cell density in the gastric antrum. Probably by inducing castain mucosal cytokine.     

Two- to four-year histological follow-up of gastric mucosa after Helicobacter pylori eradication.

In a 2- to 4-year prospective study, the reversibility of gastritis after Helicobacter pylori eradication was analysed. Sixty-three H. pylori-positive, chronic duodenal ulcer patients were studied after the successful eradication of bacteria in the period from 1990 to 1993. H. pylori eradication was obtained by triple antimicrobial regimens (colloidal bismuth subcitrate, amoxycillin, and metronidazole) applied for at least 14 days. The criteria for eradication were the absence of bacteria from two antral and two body of stomach biopsies stained with haematoxylin, eosin, and Warthin Starry, and a negative antral biopsy culture. The same diagnostic procedures were repeated, at regular follow-up endoscopies, each year for up to 4 years. Neutrophil-granulocyte infiltration of gastric mucosa disappeared in 2 months after bacterial eradication. Mononuclear cellular infiltration was disappearing with statistical significance up to the second year and normal mucosa was observed in the majority of patients in the fourth year of follow-up. Degeneratively changed lymphoid aggregates were also present in the fourth year in the antrum (12.5 per cent of patients) and in the body of stomach (14 per cent of patients). There was no significant change in antral intestinal metaplasia during the 4 years of follow-up. Antral atrophy declined significantly in the period from 1 to 3 years of follow-up. In conclusion, 3-4 years are needed for gastric mucosa to become normal after H. pylori eradication, although some residual lymphoid aggregates persist even after that period.     

Helicobacter pylori & gastric disease

Since the discovery of Helicobacter pylori(H. pylori), causal linkage between H. pylori infection and some of gastric disease has been generally accepted from the results of many studies. Indeed the usefulness of H. pylori eradication therapy for acute gastritis, peptic ulcer, gastric polyp and MALT lymphoma etc. has been reported. In the low grade MALT lymphoma, the regression rate by this therapy is about 70%. On the other hand, we should pay the caution to several adverse effects, such as drug resistance and GERD, of H. pylori eradication therapy. However, based on the several results of comparative studies between antibiotic therapy and the other one, the antibiotic therapy for peptic ulcer is only covered by national health insurance at present. The reversibility of gastric precancerous conditions such as mucosal atrophy, intestinal metaplasia and dysplasia by antibiotic therapy has been studied, but its significance is not clear yet. In animal experiment, H. pylori infection induced gastric adenocarcinoma in Mongolian Gerbils. However, this phenomenon is limited to this kind of animal only. To proof the causal link between H. pylori infection and genesis of gastric cancer in human being, clinical intervention trials are ongoing in the world. If these trials can clarify it, the H. pylori eradication therapy will be established as preventive measure for gastric carcinogenesis.     

Campylobacter pylori is associated with chronic gastritis but not with active peptic ulcer disease

Campylobacter pylori is supposed to be involved in the pathogenesis of gastroduodenal peptic ulcer diseases and chronic gastritis. In order to study whether the Campylobacter pylori in the stomach of peptic ulcer patients is related to ulcer itself or to a co-existing chronic gastritis, we examined the frequency of the bacteria in Giemsa stained histological sections of biopsy specimens from a series of patients with active peptic ulcer and from series of non-ulcer control subjects. We found no difference in the frequency of Campylobacter- positive cases between ulcer patients and non-ulcer controls when the comparison was done within the same category of chronic gastritis; e.g., within the category of chronic superficial gastritis 74% and 78% of cases showed the bacteria in antral biopsies from ulcer patients and from non-ulcer controls, respectively. In both ulcer patients and control subjects, in similar way in both antral and body mucosa, the Campylobacter pylori was strongly associated with chronic superficial gastritis but was more weakly associated with chronic atrophic gastritis, and the bacteria were only occasionally seen in normal mucosa. We conclude that Campylobacter pylori is associated with chronic gastritis in peptic ulcer patients but is not related to active ulcer.     

Helicobacter pylori infection affects eosinophilic cationic protein in the gastric juice of patients with idiopathic chronic urticaria

BACKGROUND: Helicobacter pylori, the main cause of gastritis and peptic ulcer, has been associated with idiopathic chronic urticaria (ICU), an immunological skin disorder of unknown origin. Eosinophilic cationic protein (ECP) is a cytotoxic molecule secreted by the activated eosinophils involved in the pathogenesis of ICU. We assessed serum/gastric juice ECP levels and gastric mucosal eosinophil infiltration in ICU patients infected or not with H. pylori and evaluated the modification after bacterium eradication. METHODS: 33 patients with ICU and 25 dyspeptic controls underwent upper gastrointestinal endoscopy for histological evaluation and assessment of H. pylori infection. One-week triple therapy was given to H. pylori-positive patients. Serum and gastric juice ECP levels, eosinophil infiltration from gastric mucosal sections and urticaria symptoms were evaluated in all patients at enrollment and 8 weeks after eradication. RESULTS: 19 of 33 (57%) ICU patients and 16 of 25 (64%) controls were found to be infected with H. pylori. Serum ECP was significantly higher in ICU patients compared to controls, regardless of infectious status. Gastric juice ECP and gastric eosinophil infiltration were significantly higher in infected ICU patients when compared both to uninfected ICU patients and controls. H. pylori eradication determined a significant decrease in gastric juice ECP and gastric eosinophil infiltration only in ICU patients. Moreover, a total or partial remission of urticaria symptoms was observed only in ICU patients in whom the bacterium was eradicated. CONCLUSIONS: Although H. pylori infection affects gastric juice ECP and eosinophil infiltration of ICU patients, the role of the bacterium in the pathogenesis of this skin disorder still remains uncertain.     

Spectrotypic analysis of antibodies to Helicobacter pylori in patients with antral gastritis and duodenal ulcer.

AIMS--To investigate the anti Helicobacter pylori (H pylori) spectrotype associated with (a) antral gastritis and duodenal ulcer; (b) the H pylori eradicating treatment. METHODS--Spectrotypic analysis was performed by isoelectric focusing and reverse blotting (IEFRB) in a cross sectional study on sera from 70 patients with antral gastritis and duodenal ulcer. In addition, a longitudinal study was performed on 40 of these patients (20 with antral gastritis and 20 with duodenal ulcer) who underwent eradicating treatment. RESULTS--The cross sectional study showed that the oligoclonal spectrotype was present in 74% of antral gastritis patients and in 85% of duodenal ulcer patients. In only a minority of subjects (23% with antral gastritis and 3% with duodenal ulcer) was a polyclonal spectrotype observed. The longitudinal study showed a reduction in the intensity of the spectrotypic bands in 5/10 antral gastritis patients with eradicated H pylori as opposed to only 2/10 patients without eradication. A reduction was also observed in 6/11 eradicated v 0/9 non-eradicated patients with duodenal ulcer. Collectively, a reduction in the spectrotype was observed in 11/21 patients (52%) who--independently of the disease--underwent H pylori eradication, as opposed to 2/19 of the non-responder patients (10.5%). The polyclonal spectrotype was found exclusively in four patients with antral gastritis, all belonging to the group without eradication of H pylori after eradicating treatment. CONCLUSIONS--The anti H pylori oligoclonal spectrotype is the most common pattern observed in patients with antral gastritis and duodenal ulcer. After H pylori eradicating treatment the spectrotype does not change qualitatively, but the polyclonal pattern seems to be predictive of a poor response to eradication.     

Helicobacter heilmannii gastritis: association with acid peptic diseases and comparison with Helicobacter pylori gastritis.

We analyzed 2 antral and 1 corpus full-thickness random endoscopic gastric mucosal samples obtained from 946 patients with duodenal ulcers (6077 biopsies) and from 281 patients with nonsteroidal anti-inflammatory drug-associated gastric ulcers (1794 biopsies). We stained tissue sections with hematoxylin and eosin and Warthin-Starry silver stain and immunostained them with polyclonal antibodies against Helicobacter pylori. Hematoxylin- and eosin-stained sections from 6 patients with Helicobacter heilmannii (18 biopsies) and 23 randomly selected patients with H. pylori (68 biopsies) were evaluated and semiquantitated for the presence of acute inflammation, chronic inflammation, glandular atrophy, intestinal metaplasia, H. pylori, H. heilmannii, lymphoid follicles, or vasodilatation. Additional specimens were obtained for H. pylori culture, a CLO test, and serologic examination. H. heilmannii was detected in 6 (0.49%) of 1227 patients (14 [0.18%] of 7871 biopsies). Of these, 4 (0.42%) of 946 were patients with duodenal ulcers (9 [0.15%] of 6077 biopsies), and 2 (0.71%) of 281 were patients with nonsteroidal anti-inflammatory drug-associated gastric ulcers (5 [0.28%] of 1794 biopsies). We found H. heilmannii with hematoxylin and eosin stain, Warthin-Starry stain, and immunoperoxidase stain for H. pylori. Culture for H. pylori was negative in the four patients with duodenal ulcers. The CLO and serologic tests were positive in three of five and five of five patients, respectively. Our results indicate that H. heilmannii, like H. pylori, is associated with peptic ulcer disease (both active and inactive gastritis) and that it preferentially colonizes the gastric antrum. The severity of the H. heilmannii-associated gastritis is less intense and lymphoid aggregates are less common than in H. pylori-associated gastritis. Morphologic detection seems to be the method of choice for detecting H. heilmanni. Immunoperoxidase stain specific for H. pylori also stains H. heilmannii, indicating cross-reacting antigenic epitopes between H. heilmannii and H. pylori.     

CagA antibodies in Japanese children with nodular gastritis or peptic ulcer disease

cagA(+) Helicobacter pylori strains have been linked to more severe gastric inflammation, peptic ulcer disease, and gastric cancer in adults, but there have been few studies of cagA in children. We examined the relationship between H. pylori cagA status and clinical status in Japanese children. Forty H. pylori-positive children were studied: 15 with nodular gastritis, 5 with gastric ulcers, and 20 with duodenal ulcers. H. pylori status was confirmed by biopsy-based tests and serum anti-H. pylori immunoglobulin G (IgG) antibody. As controls, 77 asymptomatic children with sera positive for anti-H. pylori IgG were enrolled. Levels of IgG antibodies to CagA in serum were measured by an antigen-specific enzyme-linked immunosorbent assay. In 16 patients with successful H. pylori eradication, posttreatment levels of CagA and H. pylori IgG antibodies also were studied. The CagA antibody seropositivities of asymptomatic controls (81.8%) and patients with nodular gastritis, gastric ulcers, and duodenal ulcers (80.0 to 95.0%) were not significantly different. Compared with pretreatment levels of CagA antibodies, posttreatment levels decreased progressively and significantly. We conclude that, as in Japanese adults, a high prevalence of cagA(+) H. pylori strains was found in Japanese children, and that there was no association with nodular gastritis or peptic ulcer disease. In the assessment of eradicative therapies, monitoring of serum anti-CagA antibodies does not appear to offer any direct benefit over monitoring of anti-H. pylori antibodies.     

Co-expression in Helicobacter pylori of cagA and non-opsonic neutrophil activation enhances the association with peptic ulcer disease

AIMS: To investigate the association of cagA positivity and non-opsonic neutrophil activation capacity in wild-type Helicobacter pylori strains with peptic ulcer disease or chronic gastritis only. METHODS: Helicobacter pylori were isolated from antral biopsies of 53 consecutive patients with chronic antral gastritis, of whom 24 had peptic ulcer disease endoscopically. The presence of cagA, a marker for the cag pathogenicity island, was determined by polymerase chain reaction with specific oligonucleotide primers, and non-opsonic neutrophil activation capacity by luminol enhanced chemiluminescence. RESULTS: The cagA gene was present in 39 of 53 (73.6%) strains, 20 of which (83.3%) were from the 24 patients with peptic ulcer disease and 19 (65.5%) from the 29 patients with chronic gastritis only. Non-opsonic neutrophil activation was found in 29 (54.7%) strains, 16 of which (66.7%) were from patients with peptic ulcer disease, and 13 (44.8%) from those with chronic gastritis. Non-opsonic neutrophil activation was found more frequently in cagA+ than cagA- strains (59% v 42.9%). Whereas four of the 14 cagA- strains and eight of the 24 non-opsonic neutrophil activation negative strains were from patients with peptic ulcer disease, only two of 24 (8.3%) peptic ulcer disease strains expressed neither cagA nor non-opsonic neutrophil activation. The cagA gene and non-opsonic neutrophil activation capacity were co-expressed in 14 of 24 (58.3%) strains from patients with peptic ulcer disease, and in nine of 29 (31%) strains from individuals with chronic gastritis. CONCLUSIONS: Positivity for cagA and non-opsonic neutrophil activation occur independently in wild-type H pylori strains. However, co-expression of the two markers enhanced the prediction of peptic ulcer disease.     

Association of Helicobacter pylori with gastritis and peptic ulcer diseases

The occurrence of Helicobacter pylori(H.pylori) and its relationship with gastric mucosa were studied by light and electron microscopy and culture of biopsy specimens from gastric mucosa of 160 patients with upper gastrointestinal symptoms. H. pylori were present in 96.6% of patients with active chronic gastritis, 100% of patients with duodenal ulcer and 76.9% of patients with gastric ulcer, while present in only 6.3% of individuals with histologically normal gastric mucosa. The bacteria colonized the antral mucosa more frequently than the body or than the duodenal cap mucosa. The bacteria were rarely seen in the intestinalized epithelium per se, but there was no significant difference in prevalence of H. pylori between gastritis with intestinal metaplasia and gastritis without intestinal metaplasia. H. pylori could be seen in close association with the surface of gastric epithelial cells below the mucus layer without evidence of intracellular parasitism, All of the strains tested were susceptible to penicillin, erythromycin, and most of them susceptible to tinidazole and bismuth salts. It is concluded that H. pylori are highly associated with gastritis and peptic ulcer diseases and its prevalence rates in patients with those diseases is higher than in developed countries. This strong association of H. pylori infection with gastritis and peptic ulcer diseases suggest a possible etiologic role for the bacterium in those diseases.     

Determination of Helicobacter pylori virulence by simple gene analysis of the cag pathogenicity island

Nucleic acid amplification was performed for five loci in the cag pathogenicity island (PAI) of Helicobacter pylori (comprising cagA, the cagA promoter region, cagE, cagT, and the left end of cagII [LEC]), and gastric inflammation in patients was evaluated. Of 204 H. pylori isolates from Japanese patients (53 with peptic ulcer, 55 with gastric cancer, and 96 with chronic gastritis), 197 (96.6%) were positive for all five loci. Two isolates (1%) were negative for all five loci, and five isolates (2.4%) were positive for only cagA and LEC. These latter seven isolates were all from patients with mild chronic gastritis. Neutrophil infiltration in gastric mucosa was significantly milder in patients infected with partially or totally deleted-PAI strains than in those with intact-PAI strains. The cagE gene was a more accurate marker of an intact cag PAI than the cagA gene, and cagE seemed to be more useful in discriminating between H. pylori strains causing different rates of disease progression.     

The pathological effect of Helicobacter pylori infection on liver tissues in mice

Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. Some reports also suggest that it causes extragastric disease, including hepatitis. In this study, the pathological changes in the liver and gall bladder in H. pylori -colonized C57BL/6 mice were investigated. Twenty mice were inoculated orally with H. pylori strain SS1, and ten controls were injected with phosphate-buffered saline. Gastric colonization with H. pylori was assessed at 2 months after inoculation. Mice were examined at 8 months by histopathology, culture for H. pylori , and PCR for specific H. pylori genes. All C57BL/6 mice infected with H. pylori for 8 months developed severe gastric mucosal inflammation. Three mice showed mild-to-moderate mutifocal hepatitis. The gall bladder mucosa of one H.  pylori -infected mouse showed thickening of the mucous membrane with mild submucosal lymphocytic infiltration. H. pylori was observed morphologically in four liver specimens and six gall bladders from infected mice by immunohistochemistry. Specific H. pylori genes were also detected in six liver samples from infected mice, six samples of bile, and two blood samples by nested PCR. Thus, H. pylori inoculated orally may reach the hepatobiliary system and cause inflammation as an independent aetiological factor. The pathway to the liver may be via the blood or the biliary system.