Eradication of Helicobacter pylori in clinical situations

Helicobacter pylori is prevalent worldwide, especially in developing countries, and is associated with several upper gastrointestinal diseases. Since it is present in over 90% of duodenal ulcer patients, empirical eradication in these patients is often recommended. In gastric ulcer patients, eradication is indicated only after the infection is confirmed. Testing for H. pylori infection should be carried out in patients with peptic ulcer hemorrhage, because eradication has been shown to reduce recurrent bleeding. Both H. pylori and NSAIDs are risk factors for peptic ulceration, and it is reasonable to screen for and eradicate H. pylori infection in peptic ulcer patients taking NSAIDs. H. pylori is a group I carcinogen for gastric adenocarcinoma, and should be eradicated for the primary prevention of this cancer. Eradication of this organism has been reported to result in regression of early low-grade mucosa-associated lymphoid tissue lymphoma. The role of H. pylori infection in the causation of gastroesophageal reflux and non-ulcer dyspepsia is not clearly established. Several tests are available for the diagnosis of H. pylori infection. These include invasive tests, such as histology, culture and urease test, and non-invasive tests, such as serology, urea breath test and stool antigen test. The choice of test is determined by clinical indication, pretest probability of infection, as well as the availability, cost, sensitivity and specificity of the test. H. pylori eradication therapy using proton pump inhibitor with clarithromycin and amoxycillin for 7 days has a success rate of 85-90%. Improved living standard and sanitation are vital in the control of H. pylori transmission and infection. Future development may include the use of vaccines against H. pylori, and therapies specifically targeting cagA strains of the bacteria.     

Helicobacter pylori and associated gastroduodenal diseases. Review article

Helicobacter pylori is a microaerophilic, Gram-negative, spiral rod, the role of which in different gastric diseases has been investigated worldwide since the beginning of the 1980s. H. pylori has been shown to be the causative agent in active chronic gastritis, and it is regularly found in patients endoscopied for duodenal ulcer. The bacterium is also frequently isolated from persons with gastric ulcer, gastric carcinoma and non-ulcer dyspepsia. Apart from cultivation of the bacterium, other diagnostic procedures include various staining methods and urease tests of gastric biopsy samples. The application of non-invasive diagnostic methods, serology and urea breath tests, is rapidly increasing. H. pylori is susceptible to several antimicrobials in vitro, but eradication of the bacterium from the gastric mucosa is not always achieved. The best results until now have been obtained with the combined use of bismuth salts and two antibiotics. In active chronic gastritis and duodenal ulcer patients, eradication of the bacteria has resulted in healing of the disease with permanent decrease of circulating antibodies and negative urease tests. H. pylori has been found worldwide and the infection shows an age-dependent increase. Man, apparently, is the reservoir of the bacterium, but the exact mechanisms of interhuman transmission are still not defined.     

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.     

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.     

Helicobacter pylori non-cytotoxic genotype enhances mucosal gastrin and mast cell tryptase.

AIMS: To determine the association, if any, between H pylori genotype and the gastric mucosal variations in the levels of gastrin, somatostatin, tryptase, and histamine. METHODS: 49 patients affected by duodenal ulcer and 48 by non-ulcer dyspepsia were studied. To identify the H pylori genotype, the presence of the cagA gene and vacA alleles m1, m2, s1, and s2 were analysed by polymerase chain reaction. Gastrin, somatostatin, tryptase, and histamine were measured in antral mucosal biopsies. RESULTS: 57 patients were infected with H pylori (30 with duodenal ulcer and 27 with non-ulcer dyspepsia). Gastrin and tryptase were increased in patients with H pylori infection, although the variations were statistically significant only for gastrin; somatostatin and histamine were not influenced by H pylori infection. In patients with non-ulcer dyspepsia the absence of the cagA gene and the presence of vacA alleles s2 and m2 were associated with higher values of tryptase and to a lesser extent of gastrin. These associations were not found in patients with duodenal ulcer. CONCLUSIONS: The cagA negative s2m2 strain of H pylori may be less dangerous for the gastric mucosa than other H pylori strains since it enhances tryptase production by gastric mucosal mast cells; this enzyme is thought to stimulate tissue turnover and favour wound healing.     

Differing degree and distribution of gastritis in Helicobacter pylori-associated diseases

Infection with Helicobacter pylori (H. pylori) causes gastritis, and may be associated with gastric and duodenal ulcers and also with such malignant diseases as MALT lymphoma and gastric carcinoma. In order to determine whether there are differences in the degree and distribution of gastritis, each patient with H. pylori gastritis only (n = 50) was matched for sex and age with four patients, one each with H. pylori-associated duodenal ulcer, gastric ulcer, gastric carcinoma or MALT lymphoma. From each patient, two biopsies were taken from the antrum and two from the corpus for histopathological examination of H. pylori gastritis. The median summed gastritis score decreases in the following order: antrum: gastric ulcer > duodenal ulcer > gastritis alone > carcinoma > MALT lymphoma, and corpus: gastric ulcer > carcinoma > MALT lymphoma > gastritis alone and duodenal ulcer. We conclude that the degree and distribution of H. pylori gastritis differs significantly among H. pylori-associated diseases. These differences may explain some of the underlying pathomechanisms associated with H. pylori infection.     

Peptic ulceration may be a hormonal deficiency disease

Evidence is reviewed that Helicobacter pylori infection may cause a deficiency of the hormone secretin that allows peptic ulcer disease to develop by impairing the body's defenses to gastric acid. Secretin is released into the circulation from the S-cells of the duodenal crypts in response to gastric acid entering the duodenum. Once in the circulation, secretin has five well-documented effects that protect the upper intestine from gastric acid: it stimulates secretion of bicarbonate rich exocrine pancreatic juice; it stimulates secretion of alkaline bile; it stimulates secretion of alkaline mucus from the duodenal submucosal glands of Brunner; it inhibits the humoral phase of gastric secretion; and it inhibits gastric motility, thereby delaying gastric emptying. Impaired secretin release and reduced duodenal S-cells have been documented in peptic ulcer patients compared with control patients. Clinical evidence that patients with H. pylori infection and peptic ulceration have increased gastric secretion and motility and decreased duodenal bicarbonate response to gastric acid, all of which normalize after eradication of the infection, could be explained by reversible impairment of the secretin mechanism. Gastric metaplasia in the duodenum with H. pylori infection is known to reduce the S-cell population. The fact that not all patients with H. pylori infection develop peptic ulceration suggests that degree of secretin deficiency determined by extent of the infection must reach a critical level for peptic ulceration to occur. Peptic ulceration may be a hormonal deficiency disease, a result of secretin deficiency caused by H. pylori infection. It may be the first example of a specific hormonal deficiency disease caused by a specific bacterial infection.     

Helicobacter pylori does not release cysteamine into gastric juice.

AIM: To determine whether Helicobacter pylori releases cysteamine into gastric juice as cysteamine is known to be ulcerogenic. METHODS: Samples of fasting gastric juice were collected from 22 individuals (four women); 10 subjects were H pylori negative. The presence of infection was confirmed by examination and culture of gastric biopsies. Cysteamine in gastric juice was measured by reversed phase gradient high performance liquid chromatography with a detection limit of 10 mumol/l. RESULTS: Cysteamine was not detected in any of the gastric juice samples or in extracts of cultured H pylori. CONCLUSIONS: If H pylori produces cysteamine then the amounts produced are insignificant and are unlikely to explain the association between H pylori infection and the development of duodenal ulcer disease.     

Helicobacter pylori infection at a university hospital in Saudi Arabia: prevalence, comparison of diagnostic modalities and endoscopic findings

The presence of Helicobacter pylori (H. pylori) was examined in 491 sequential patients, complaining mainly of epigastric pain, by three biopsy-based methods (rapid urease, histology, and culture), and by a serological test, enzyme immunosorbent assay, (ELISA). H. pylori was detected in 341 (70%) of 491 patients examined by histology, 287 (59%) by rapid urease test, whereas 385 (78%) were seropositive for H. pylori immunoglobulins by ELISA. None of the test methods used was independently sufficient to make an etiologic diagnosis of H. pylori infection. The endoscopic findings revealed that 315 (69%) of 456 patients with non-ulcer dyspepsia, 17 (74%) of 23 patients with duodenal ulcer, 7 (78%) of 9 patients with gastric ulcer, and 2 (67%) of 3 patients with gastric cancer were H. pylori positive. No statistically significant correlation was found between the endoscopic and the histopathological findings. A significant correlation was found between H. pylori infection and the histopathological gradings of gastritis (P < 0.001).     

Clinicopathological features of duodenal bulb biopsies and their relationship with upper gastrointestinal diseases

AimTo assess the prevalence of the lesions in duodenal bulb mucosa and the relationship between duodenal lesions and upper gastrointestinal diseases, including helicobacter pylori infection.MethodsClinical, endoscopic and pathological data of the cases with duodenal bulb and gastric mucosal biopsy from January 2005 to May 2017 were analyzed retrospectively.ResultsA total of 3540 patients were enrolled. The biopsy from protuberant lesions with endoscopic morphology are mostly duodenal gastric heterotopia or adenoma. The biopsy from duodenal ulcers are often observed in inflammatory changes and gastric metaplasia.Patients with gastric heterotopia had a significantly lower prevalence of chronic atrophic gastritis, intestinal metaplasia, and gastric ulcer; and much higher prevalence of gastroesophageal reflux disease and gastric fundic polyps.Patients with gastric metaplasia had been positively associated with gastroesophageal reflux disease, and negatively associated with gastric fundic polyps.There were positive correlation between helicobacter pylori infection and duodenal active inflammation, Brunner gland hyperplasia, gastric metaplasia and duodenal ulcer. However, Patients with gastric heterotopia in bulb had been negatively associated with helicobacter pylori infection.ConclusionsThe mucosa lesions in duodenal bulb were associated with concurrent gastric fundic gland polyps, gastroesophageal reflux disease, duodenal ulcer, and helicobacter pylori infection.     

Functional promoter polymorphisms of macrophage migration inhibitory factor in peptic ulcer diseases

Macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator, which plays a pivotal role in inflammatory and immune diseases. We attempted to clarify the association of functional polymorphisms of MIF gene promoter with the development of gastro-duodenal ulcer. The study was performed in 471 stocked DNAs obtained from the subjects, including 93 healthy volunteers, with no evidence of gastric malignancy. We employed the PCR-SSCP method to detect gene polymorphisms. In all 471 DNAs, 92 and 43 were obtained from gastric and duodenal ulcer patients, respectively. By an unadjusted analysis, infection with Helicobacter pylori (H. pylori), male gender and non-steroidal anti-inflammatory drug (NSAID/aspirin) use were significantly associated with a risk for developing a gastric ulcer, whereas MIF promoter polymorphisms were not. On the other hand, infection with H. pylori, male gender and 7-CATT repeat at position -794 were significantly associated with the development of a duodenal ulcer, whereas NSAID/ aspirin use was not. By the analysis after adjustment for age, gender, NSAID/aspirin use and H. pylori infection status, 7/7-CATT homozygote had a significantly increased risk for the development of duodenal ulcers (OR, 6.31; 95% CI, 1.50-26.6; p=0.012). No factors were significantly associated with the development of peptic ulcers in NSAID/aspirin users. Our results suggested that tetranucleotide repeat polymorphism of MIF gene promoter might be associated with the development of duodenal ulcers.     

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.     

The prevalence of lymphoid follicles in Helicobacter pylori associated gastritis in patients with ulcers and non-ulcer dyspepsia.

AIMS--To determine the prevalence of lymphoid follicles in Helicobacter pylori positive and negative gastritis in antral and body type gastric mucosa in patients with non-ulcer dyspepsia (NUD), duodenal ulcer, or gastric ulcer; to correlate follicle presence with patient age; to evaluate the correlation between the prevalence of lymphoid follicles and active and inactive gastritis and its severity; and to assess the positive predictive value of lymphoid follicle prevalence with respect to H pylori infection. METHODS--Gastric biopsy specimens, graded according to the Sydney system, from 337 patients were studied. RESULTS--Lymphoid follicles occurred more often in antral mucosa (78%) than in body type mucosa (41%) and were observed in 85% of patients with H pylori positive gastritis. There was no significant difference between NUD and gastric and duodenal ulcer disease with regard to the presence of lymphoid follicles. The positive predictive value of the presence of lymphoid follicles in H pylori infection was 96%. Lymphoid follicles were more commonly observed in patients aged between 10 and 29 years. Lymphoid follicles were more frequently found in pangastritis of all subtypes than in antral gastritis and also in active gastritis than in inactive gastritis. The presence of lymphoid follicles correlated strongly with the degree and severity of gastritis. CONCLUSION--Lymphoid follicles are a constant morphological feature of H pylori associated gastritis.     

Helicobacter pylori infection and the development of gastric cancer

BACKGROUND: Although many studies have found an association between Helicobacter pylori infection and the development of gastric cancer, many aspects of this relation remain uncertain. METHODS: We prospectively studied 1526 Japanese patients who had duodenal ulcers, gastric ulcers, gastric hyperplasia, or nonulcer dyspepsia at the time of enrollment; 1246 had H. pylori infection and 280 did not. The mean follow-up was 7.8 years (range, 1.0 to 10.6). Patients underwent endoscopy with biopsy at enrollment and then between one and three years after enrollment. H. pylori infection was assessed by histologic examination, serologic testing, and rapid urease tests and was defined by a positive result on any of these tests. RESULTS: Gastric cancers developed in 36 (2.9 percent) of the infected and none of the uninfected patients. There were 23 intestinal-type and 13 diffuse-type cancers. Among the patients with H. pylori infection, those with severe gastric atrophy, corpus-predominant gastritis, and intestinal metaplasia were at significantly higher risk for gastric cancer. We detected gastric cancers in 21 (4.7 percent) of the 445 patients with nonulcer dyspepsia, 10 (3.4 percent) of the 297 with gastric ulcers, 5 (2.2 percent) of the 229 with gastric hyperplastic polyps, and none of the 275 with duodenal ulcers. CONCLUSIONS: Gastric cancer develops in persons infected with H. pylori but not in uninfected persons. Those with histologic findings of severe gastric atrophy, corpus-predominant gastritis, or intestinal metaplasia are at increased risk. Persons with H. pylori infection and nonulcer dyspepsia, gastric ulcers, or gastric hyperplastic polyps are also at risk, but those with duodenal ulcers are not.     

Histological study of chronic gastritis from the United Arab Emirates using the Sydney system of classification.

AIMS--To determine the prevalence of Helicobacter pylori in five main nationality groups with gastric ulcer, duodenal ulcer, and non-ulcer dyspepsia; and to determine the histopathological types of gastritis and assess the graded variables of Helicobacter associated gastritis. METHODS--Gastric antral and corpus biopsy specimens from 437 patients were examined for the prevalence of H pylori, 337 of which were classified and graded histologically according to the Sydney system. RESULTS--The overall colonisation rate of H pylori was 90%, and there was no significant difference between groups of different ethnic origins. The colonisation rates were 99%, 89%, and 78% in patients with duodenal ulcer, non-ulcer dyspepsia, and gastric ulcer, respectively. Helicobacter associated gastritis was the most common form of chronic gastritis (87%). H pylori density was greater in the antrum than the body. Gastric atrophy in helicobacter associated gastritis was seen in 54% of the cases (43% grade I, 10% grade II, 1% grade III) and increased the older the patients. Atrophy of the corpus alone was very rare (1%). Atrophy and intestinal metaplasia were more prevalent in patients with gastric ulcer than duodenal ulcer. CONCLUSION--The colonisation rate of H pylori was similar in the five groups studied and was almost invariably present in gastric biopsy specimens in patients with duodenal ulcer. H pylori associated gastritis was the most common form of gastritis. Atrophy was mainly of low grade and increased the older the patient.     

Giardia lamblia trophozoites in gastric biopsies

To assess the prevalence of gastric giardiasis in gastric biopsies of patients with carcinoma stomach and in patients taking treatment for duodenal ulcer. Gastric biopsy specimens from 54 patients of carcinoma stomach and 100 antral biopsies from patients taking treatment for duodenal ulcer were included in the study. Sections were stained with haematoxylin and eosin, methylene blue and May Grunwald-Giemsa stains and examined for presence of Giardia lamblia trophozoites. Eight out of 54 (14.9%) biopsies of gastric carcinoma patients harboured trophozoites of Giardia lamblia. Associated H. pylori infection was present in all biopsies (8/8; 100%). Atrophy and intestinal metaplasia was present in 62.5% (5/8) and 25% (2/8) cases respectively. Sections from seven out of 35 patients (20%) taking treatment for duodenal ulcer showed presence of G. lamblia. H. pylori infection, gastritis and atrophy were found in 85.7% (6/7), 71.4% (5/7) and 28.6% (2/7) cases respectively. First gastric biopsy in these patients was negative for G. lamblia but 2nd and 3rd biopsies were positive. A careful search for G. lamblia trophozoites should be made while examining the gastric biopsies, especially in patients with carcinoma stomach, intestinal metaplasia, atrophic gastritis and those taking treatment for duodenal ulcer. This may help in indirect diagnosis of clinically unsuspected cases of intestinal giardiasis and may explain persistence of vague upper gastrointestinal tract (UGIT) symptoms despite clearance of H. pylori in patients on anti-ulcer therapy.     

Helicobacter pylori.

Helicobacter pylori is a gram-negative bacterium which causes chronic gastritis and plays important roles in peptic ulcer disease, gastric carcinoma, and gastric lymphoma. H. pylori has been found in the stomachs of humans in all parts of the world. In developing countries, 70 to 90% of the population carries H. pylori. In developed countries, the prevalence of infection is lower. There appears to be no substantial reservoir of H. pylori aside from the human stomach. Transmission can occur by iatrogenic, fecal-oral, and oral-oral routes. H. pylori is able to colonize and persist in a unique biological niche within the gastric lumen. All fresh isolates of H. pylori express significant urease activity, which appears essential to the survival and pathogenesis of the bacterium. A variety of tests to diagnose H. pylori infection are now available. Histological examination of gastric tissue, culture, rapid urease testing, DNA probes, and PCR analysis, when used to test gastric tissue, all require endoscopy. In contrast, breath tests, serology, gastric juice PCR, and urinary excretion of [15N]ammonia are noninvasive tests that do not require endoscopy. In this review, we highlight advances in the detection of the presence of the organism and methods of differentiating among types of H. pylori, and we provide a background for appropriate chemotherapy of the infection.     

CagA和机体免疫反应在幽门螺杆菌致病中的作用及相互关系

目的　探讨幽门螺杆菌 (Helicobacterpylori,Hp)菌型差异和机体免疫反应在Hp致病中的作用及其相互关系。方法　采用间接ELISA法检测了 175例患者血清抗HpCagA IgG和抗HpIgE。结果　①Hp感染者抗HpCagA IgG的阳性率 (80 % )明显高于抗HpIgE(5 8 2 9% ,P <0 0 1)。②血清抗HpCagA IgG在慢性活动性胃炎 (ACG)和十二指肠球部溃疡 (DU)患者显著高于胃溃疡 (GU)、胃癌(GCa)、慢性非活动性胃炎 (NACG)和对照组 (P <0 0 1) ,而后 4组之间差异无显著性。③血清抗HpIgE在ACG显著高于DU、GU、GCa、NACG和对照组 (P <0 0 1) ,并且在中重度胃炎显著高于轻度胃炎(P <0 0 0 1)。④血清抗HpCagA IgG和抗HpIgE无明显相关性 (r=0 2 45 9,P >0 0 5 )。结论　CagA和血清抗HpIgE参与了Hp的致病过程 ,但是两者之间无明显相关性 ,并且它们在疾病中的含量也有一定差异 ,这说明二者在Hp的致病过程中是相互独立的因素 ,Hp感染引起疾病是多因素的综合作用。