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Double gastric infection with Helicobacter pylori and non-Helicobacter pylori bacteria during acid-suppressive therapy: increase of pro-inflammatory cytokines and development of atrophic gastritis.

BACKGROUND: Long-term acid suppression may accelerate the development of atrophic gastritis in Helicobacter pylori-positive subjects. The pathogenetic mechanism remains unclear. AIM: To test the hypothesis that gastric double infection with H. pylori and non-H. pylori bacterial species-during acid suppression-may result in an enhanced inflammatory response, contributing to the development of atrophic gastritis. PATIENTS AND METHODS: A consecutive series of patients with gastro-oesophageal reflux disease undergoing treatment with proton pump inhibitors (n=113) or histamine2-receptor antagonists (H2-RAs) (n=37), and 76 non-treated dyspeptic controls were investigated. Gastric mucosal H. pylori and non-H. pylori bacteria, histological gastritis, H. pylori serology, and circulating interleukin (IL)-1beta, IL-6, and IL-8 were examined. RESULTS: Patients on acid suppression with either proton pump inhibitors or H2-RAs had a similar prevalence of H. pylori infection to the controls, but a higher prevalence of non-H. pylori bacteria (61% and 60% vs. 29%, P < 0.0001 and P < 0.002). Both the presence of H. pylori and non-H. pylori bacteria were independent risk factors of atrophic gastritis (antrum: relative risks (RRs), 10.1 and 5.07; corpus: RRs, 11.74 and 6.38). A simultaneous presence of H. pylori and non-H. pylori bacteria was associated with a markedly increased risk of atrophic gastritis (antrum: RR, 20.25; corpus: RR, 20.38), compatible with a synergistic effect. Furthermore, the simultaneous presence of both types of bacteria was associated with higher cytokine levels than in patients without any type of bacteria. This increase was also greater than in patients with H. pylori infection alone (P < 0.001, for both IL-1beta and IL-8). SUMMARY AND CONCLUSIONS: H. pylori-positive patients on long-term acid inhibition displayed three features: non-H. pylori bacterial growth; increased cytokine levels; and a higher risk of atrophic gastritis. We suggest that double infection with H. pylori and non-H. pylori bacteria is a major factor in the development of atrophic gastritis during gastric acid inhibition.

Adult↗

Helicobacter pylori infection: mechanism of colonization and functional dyspepsia Reduced colonization of gastric mucosa by Helicobacter pylori in mice deficient in interleukin-10.

BACKGROUND AND AIMS: Interleukin-10 (IL-10) is a potent anti-inflammatory and immunoregulatory cytokine. Mice deficient in IL-10 production (IL-10-/-mice) develop a spontaneous chronic enterocolitis, suggesting that IL-10 is an important regulator of the mucosal immune response in vivo. The objective of this study was to determine the role of endogenous IL-10 in the host defense against gastric colonization by Helicobacter pylori by using IL-10-deficient mice. METHODS: The IL-10-/-mice were inoculated intragastrically with a mouse-adapted H. pylori isolate (Sydney Strain 1). Gastric colonization by H. pylori (biopsy urease test and bacterial colony counts), serum levels of H. pylori-specific immunoglobulin (Ig) M, A, G, isotypes of IgG, and the gastric mucosal inflammatory scores were determined 6 weeks after inoculation. Results were compared with those obtained from H. pylori-infected control mice (IL-10+/-mice). RESULTS: The colonization of gastric mucosa by H. pylori was reduced approximately 100-fold (P < 0.0001) in IL-10-/-mice (log10 4.87 +/- 0.26CFU/g tissue) as compared to IL-10+/-mice (log10 6.64 +/- 0.22 CFU/g tissue). Furthermore, IL-10-/-mice infected with H. pylori had significantly higher H. pylori-specific IgA and IgG antibodies in serum (P < or = 0.01), and developed much more severe chronic active gastritis than infected IL-10+/-mice. The median scores of the infiltration of gastric mucosa by mononuclear cells and neutrophils were up to threefold higher in IL-10-/-mice than they were in IL-10+/-mice. CONCLUSION: Our studies suggest that endogenous IL-10 is an inhibitor of the protective immune response to H. pylori infection. Interleukin-10 participates in the downregulation of H. pylori-induced gastric inflammatory responses, which apparently confers a survival advantage to the organism promoting more effective colonization of gastric mucosa.

Animals↗

Influence of oral Helicobacter pylori on the success of eradication therapy against gastric Helicobacter pylori.

BACKGROUND: The goal of this study was to see whether Helicobacter pylori (H. pylori) in the oral cavity might adversely affect the outcome of eradication therapy for gastric H. pylori. MATERIALS AND METHODS: Forty-seven patients (36 males, 11 females) with gastric H. pylori infection were enrolled in this study. Gastric H. pylori infection was confirmed by both immunohistological staining with anti-H. pylori antibody and bacterial culture of biopsy specimens. The therapeutic regimen consisted of 30 mg/day lansoprazole, 750 mg/day metronidazole, and 400 mg/day clarithromycin administered for 2 weeks. A fragment of the H. pylori urease gene was amplified by nested PCR for DNA extracted from saliva and dental plaque from the same patients. We examined the correlation between the gastric eradication success rate and the prevalence of H. pylori in the oral cavity as determined by PCR before and after the eradication therapy. RESULTS: The eradication success rate was significantly lower in the oral H. pylori-positive cases (12/23, 52.1%) than in the negative cases (22/24, 91.6%) at 4 weeks after the therapy (p =. 0028). Two years later, only 16 of the 23 (69.5%) oral H. pylori-positive cases were disease-free, as compared to 23 of the 24 (95.8%) oral H. pylori-negative cases (p =.018). CONCLUSIONS: H. pylori in the oral cavity affected the outcome of eradication therapy and was associated with a recurrence of gastric infection. We recommend that oral H. pylori should be examined by nested PCR and, if positive, should be considered a causal factor in refractory or recurrent cases.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Prospective screening of dyspeptic patients by Helicobacter pylori serology: a safe policy? The Italian Helicobacter pylori Study Group.

BACKGROUND AND STUDY AIMS: Endoscopic screening of all dyspeptic patients is not cost-effective, nor is it feasible in many health-care delivery systems. To select the most appropriate candidates, various preendoscopic screening strategies have been proposed, some of which include Helicobacter pylori serology and patient age. We assessed the value of these two criteria in preendoscopic screening of a large series of dyspeptic patients, and compared the results obtained in a referral hospital (university center with an extensive H. pylori research program) with those in nonreferral hospital (participating centers that did not have such a program). PATIENTS AND METHODS: Blood samples for determination of anti-H. pylori IgG antibody were collected from patients with uninvestigated dyspepsia undergoing endoscopy at one referral hospital and in 93 nonreferral hospitals throughout Italy. For IgG antibody assay, an in-house enzyme-linked immunosorbent assay (ELISA) technique was used in the referral hospital, while a commercial kit was used in the nonreferral hospitals. RESULTS: A total of 1638 patients were evaluated at the referral hospital (845 men and 793 women, mean age 46.1 years, range 18-89), and 3281 at the nonreferral hospitals (1718 men and 1563 women, mean age 48.8, range 18-96), respectively. If endoscopy had not been performed in patients who were seronegative for H. pylori and younger than 45 years, 19% versus 17.5% of the tests would have been avoided in the referral and nonreferral hospitals, respectively, while six of 304 ulcers (2%) and no cancers would have been missed versus 35 of 557 ulcers (6.3%) and two of 557 cancers (0.3%). CONCLUSIONS: A screening strategy based on age and H. pylori serology is a valid means of selecting dyspeptic patients for endoscopy; however, the policy needs further refinement for use in nonreferral hospitals.

Adolescent↗

Intramucosal Helicobacter pylori in the human and murine stomach: its relationship to the inflammatory reaction in human Helicobacter pylori gastritis.

Intramucosal Helicobacter pylori (H. pylori) has been described in biopsy tissues and culture systems. However, the association of intramucosal H. pylori with histopathologic features has not been evaluated. The purpose of this study is to investigate the relationship between intramucosal H. pylori and inflammatory reactions in H. pylori infection. In 113 randomly selected human gastric biopsies and 20 murine stomachs, which were inoculated with SSI every day for a week, immunohistochemical analysis for intramucosal H. pylori was done and correlated with histologic parameters. Electron microscopic examination was done on murine stomachs. H. pylori infection was present in 104 gastric biopsies and 17 murine stomachs. Intraepithelial immunopositivity for H. pylori was detected in 27 of 104 (26%) biopsies and in 11 of 17 (65%) murine stomachs. Lamina proprial immunopositivity for H. pylori was present in 51 of 104 (48%) biopsies. Neutrophil-associated immunopositivity for H. pylori was observed in 22 of 90 (24%) biopsies with H. pylori chronic active gastritis. Lamina proprial and neutrophil-associated immunopositivity for H. pylori correlated significantly with the density of H. pylori and the grade of acute inflammatory reaction in H. pylori gastritis. Intramucosal location of H. pylori itself or its antigen is closely associated with acute inflammatory reactions and may play an important role in establishing a persistent infection in chronic H. pylori gastritis. Furthermore, lamina proprial and/or neutrophil-associated H. pylori appears to be more important than intraepithelial H. pylori in acute inflammatory reactions of H. pylori gastritis.

Animals↗

Seroprevalence of Helicobacter pylori infection in inflammatory bowel disease: is Helicobacter pylori infection a protective factor?

BACKGROUND: The mechanisms for the observed low prevalence of Helicobacter pylori infection in inflammatory bowel disease (IBD) are unknown, but might be important for the pathogenesis of IBD. We have studied the seroprevalence of H. pylori in different categories of IBD and evaluated the role of medical therapy, smoking and social status. We also analysed the effect of seropositivity on the age of onset of IBD in order to find possible evidence for the protective effect of the infection. METHODS: We studied 296 (mean age 43 years, range 18-79; women 144) unselected patients with IBD, including 185 with ulcerative colitis (UC). 94 with Crohn disease (CD), and 17 with indeterminate colitis (IC). Seventy healthy age- and sex-matched subjects served as controls. Serum samples were studied for H. pylori antibodies. Detailed clinical history was obtained from patient records and by face-to-face interview. RESULTS: The prevalence of H. pylori infection was lower in IBD patients (24%) than in controls (37%; P = 0.029), and in CD lower (13%) than in UC (30%; P = 0.002). Seropositivity was not related to sulphasalazine treatment or smoking. Age of onset of IBD was higher in seropositive (mean 40 years) than in seronegative patients (30 years: P < 0.001). The age of onset of IBD showed unimodal distribution in H. pylori seronegative patients, with a peak between 30 and 40 years, although there was some evidence of bimodality in CD. In contrast, H. pylori seropositive patients had clear bimodal pattern with peaks at 20-40 and 50-60 years of age. CONCLUSIONS: Our results confirm the low prevalence of H. pylori infection in IBD, and in particular in CD. The significantly higher age of onset and bimodal pattern of age-specific incidence in seropositive IBD patients suggest that H. pylori infection significantly modifies the development of IBD and may have a protective effect.

Adult↗

Effect of helicobacter pylori eradication on sideropenic refractory anaemia in adolescent girls with Helicobacter pylori infection.

We investigated the effect of Helicobacter pylori eradication on sideropenic refractory anaemia in adolescent girls with H. pylori-associated antral gastritis without evidence of haemorrhage or clinical symptoms other than sideropenic anaemia. We conducted an open therapeutic trial in 21 adolescent girls aged 15-17 y with sideropenic refractory anaemia, which was defined as iron-deficiency anaemia refractory to oral iron therapy for 3 mo. All subjects underwent gastroduodenal endoscopy. Thirteen patients with confirmed H. pylori infection were given a 2-wk course of triple therapy and 6 wk of oral ferrous sulfate. We compared the mean levels of haemoglobin and serum ferritin among the "initial sample" (the time when the sampling was done before treatment with oral iron), "before eradication" (the time prior to triple therapy for eradication after subjects had been given oral iron for 3 mo) and "after eradication" (the time when the follow-up endoscopy was performed) data in 11 subjects in whom H. pylori infection was eradicated. Haemoglobin levels (g/dl) were 8.6+/-1.9, 8.6+/-1.4 and 11.3+/-2.3, respectively. Serum ferritin levels (microg/l) were 4.6+/-2.4, 4.2+/-2.3 and 17.5+/-6.7, respectively. After eradication of H. pylori, mean levels of haemoglobin (p = 0.0002) and serum ferritin (p = 0.0002) showed a prominent increase between "before eradication" and "after eradication". In conclusion, adolescent girls with sideropenic refractory anaemia should be evaluated for H. pylori infection. If H. pylori infection is coexistent, its eradication along with iron supplementation could correct the anaemia.

Adolescent↗

Application of Maastricht 2-2000 guidelines for the management of Helicobacter pylori among specialists and primary care physicians in israel: are we missing the malignant potential of Helicobacter pylori?

BACKGROUND: The Maastricht 2-2000 guidelines on the current management of Helicobacter pylori infection were recently adopted by the Israeli Gastroenterological Association. GOAL: To determine the impact of these clinical guidelines on the current knowledge, attitudes, and management of H. pylori among primary care physicians, hospital internists, and gastroenterologists in Israel. STUDY: Self-administered, voluntary, anonymous questionnaires were given personally to 229 physicians, 73 primary care physicians, 71 internists, and 85 gastroenterologists. The questions evaluated 4 main issues in the management of H. pylori: (1). the optimal diagnostic test, (2). indications for eradication, (3). combination and duration of triple therapy, and (4). the need for confirmation following eradication. RESULTS: There were significant variations in the adherence of those recommendations among gastroenterologists, internists, and primary care physicians. Specifically, 94.1% of gastroenterologists and 88.9% of internists consider the urea breath test the test of choice for H. pylori diagnosis compared with 60.0% of the primary care physicians. Significant differences in the eradication indications for mucosa-associated lymphoid tissue (MALT) lymphoma, first-degree relatives of gastric cancer patients, atrophic gastritis, functional dyspepsia, and concomitant use of nonsteroidal antiinflammatory drugs were demonstrated among gastroenterologists and the other groups. CONCLUSIONS: Primary care physicians may not be aware of important indications for diagnosis and eradication of H. pylori related to the risk of gastric malignancy or concomitant use of nonsteroidal antiinflammatory drugs. Public health agencies may need to increase penetration of the Maastricht 2000 recommendations to primary care physicians.

Amoxicillin↗

Five- to 7-year-old children with Helicobacter pylori infection are smaller than Helicobacter-negative children: a cross-sectional population-based study of 3,315 children.

OBJECTIVE: To test whether Helicobacter pylori-positive children are smaller and weigh less than H pylori-negative children. DESIGN: Cross-sectional population-based study. PARTICIPANTS: In 3,315 5-to 7-year-old preschool and school children, the putative influence of H pylori infection on growth was investigated. Standing height and weight were analyzed in relation to H pylori infection. The diagnosis of H pylori infection was established by 13C-urea-breath test. RESULTS: The prevalence of H pylori infection in boys was 7.2% (95% confidence interval, 5.9-8.9; n = 1,550) and in girls was 6.1% (95% confidence interval, 4.9-7.3; n = 1,552) H pylori-positive children were smaller than noninfected children (117.6 +/- 5.5 cm vs. 118.9 +/- 5.7 cm; P < 0.01). Although H pylori-positive boys were 2.06 cm smaller than H pylori-negative boys (117.4 +/- 5.6 cm vs. 119.5 +/- 5.7 cm; P < 0.001), the difference in girls was not significant (117.9 +/- 5.3 cm vs. 118.4 +/- 5.7 cm). When standing height was adjusted for age, the found differences were more pronounced. Differences between the infected and noninfected children with regard to body weight were not significant (22.4 +/- 4.0 kg vs. 22.1 +/- 4.0 kg), nor was there a significant difference with regard to body-mass index. However, boys with H pylori infection had a lower weight than noninfected boys (21.6 +/- 3.3 kg vs. 22.6 +/- 4.0 kg; P < 0.01), but in girls, these differences were not observed (22.2 +/- 4.0 vs. 22.8 +/- 4.6 kg, respectively). When weight was adjusted for age, H pylori -positive children also had a lower weight than H pylori -negative children because of the lower weight of boys. CONCLUSIONS: H pylori infection is associated with growth delay, growth retardation, or both in affected children.

Body Height↗

Helicobacter pylori Stool Antigen test: a reliable non-invasive test for the diagnosis of Helicobacter pylori infection in children.

OBJECTIVE: To evaluate the Helicobacter pylori Stool Antigen (HpSA) test for the diagnosis of H. pylori infection in children. DESIGN AND SETTING: Prospective cohort study in an academic medical centre. PATIENTS AND METHODS: A total of 106 consecutive children who underwent gastroscopy were included. Biopsy specimens were sampled from the gastric antrum and corpus for the assessment of H. pylori infection by culture and histology. A patient was defined to be H. pylori positive if the results of culture and/or histology proved to be H. pylori positive; a patient was defined to be negative if both test results were negative. All children provided a stool sample within 2 days of gastroscopy. H. pylori antigens in faeces were assessed by an enzyme immunoassay (Premier HpSA, Meridian Diagnostics, Inc., Cincinnati, OH, USA). RESULTS: The mean age of included patients was 8.5 years (range 1-18.5). Thirty patients were H. pylori positive and 76 patients were H. pylori negative. Using the recommended cut-off values of 0.140 optical density (OD) and 0.159 OD, sensitivity and specificity of 100% and 92% were found. The positive and negative predicting values were 83% (30/36) and 100% (70/70), respectively. CONCLUSION: The HpSA test is an accurate test for the diagnosis of H. pylori infection in children, and might therefore be a good alternative for diagnostic tests such as the 13C-urea breath test (UBT).

Antigens, Bacterial↗

No Helicobacter pylori, no Helicobacter pylori-associated peptic ulcer disease.

Virtually all duodenal ulcers (DUs) and the vast majority of gastric ulcers (GUs) are the consequence of Helicobacter pylori-associated inflammation. In DUs, the inflammation is maximal in the antrum and is associated with gastric metaplasia in the bulb. Gastrin homeostasis is disturbed by H. pylori gastritis and there is robust acid secretion. Successful eradication of the infection cures the ulcer diathesis. Amalgamated figures for ulcer relapse per year in H. pylori-positive DUs are > 60% compared with 2.6% for H. pylori-negative DU patients. The corresponding figures for GU are > 50% for H. pylori-positive and 2.0% for H. pylori-negative individuals. This striking difference in relapse rate persists, as the re-infection rate in the developed world is < 1% per year. Recurrent bleeding in bleeding-prone DUs is essentially abolished after cure of the infection. Proton pump inhibitors (PPIs) are increasingly used in eradication regimens. PPIs have intrinsic antimicrobial activity. MICs for lansoprazole (LAN) are lower than for omeprazole (OME). Two weeks of triple therapy (bismuth, tetracycline, imidazole) has, on average, a superior eradication efficacy (> or = 90%) compared with dual therapy (PPI, amoxycillin or clarithromycin) (> or = 80%). When a combination of PPI and two antibiotics has been used, results comparable to triple therapy have been reported. However, the side-effects profile and patient acceptability of PPI plus one or two antibiotic regimens are better than for traditional triple therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗

Effect of dietary anti-Helicobacter pylori-urease immunoglobulin Y on Helicobacter pylori infection.

Recently, chicken egg yolk was recognized as an inexpensive antibody source, and the therapeutic usefulness of egg yolk immunoglobulin Y (IgY) in oral passive immunization has been investigated. Although multiple antibiotic treatments eradicate most Helicobacter pylori (H. pylori) infections, therapy fails in 10-15% of cases due to the development of drug resistance. Consequently, it is important that new, more broadly based therapies for the treatment of H. pylori infection should be identified. The present study evaluated the effect, on H. pylori infection, of IgY prepared from egg yolk of hens immunized with H. pylori urease (anti-HpU IgY). Seventeen asymptomatic volunteers diagnosed as H. pylori-positive by the 13C-urea breath test (UBT) were orally administered anti-HpU IgY for 4 weeks. Four weeks later, UBT values were significantly decreased although no case showed H. pylori eradication. An H. pylori-positive 53-year-old female gastritis patient administered anti-HpU IgY plus lansoprazole for 8 weeks showed a decrease in serum pepsinogen (PG) I and UBT values as well as an increase in the PG I/II ratio. In conclusion, anti-HpU IgY may mitigate H. pylori-associated gastritis and partially attenuate gastric urease activity. Furthermore, anti-HpU IgY combined with antacids appears to ameliorate gastric inflammation. These encouraging results may represent a novel approach to the management of H. pylori-associated gastroduodenal disease.

Adult↗

Evaluation of anti-Helicobacter pylori IgG2 antibody for the diagnosis of Helicobacter pylori infection in western and Chinese populations.

BACKGROUND: The performance of commercial Helicobacter pylori diagnostic kits developed for particular geographic regions has often been found to be of poor diagnostic value when applied to other regions, possibly because of infections being caused by different H. pylori strains in different regions. AIM: To evaluate the performance of an IgG2 anti-H. pylori enzyme-linked immunoassay test (Helirad Alert) for detection of H. pylori infection in both Australian and Hong Kong (Chinese) subjects. METHODS: Serum samples were tested for H. pylori specific IgG2 and IgG antibodies by enzyme-linked immunoassay kits using identical antigen preparation in 168 Australian and 160 Hong Kong (Chinese) subjects diagnosed with dyspepsia. RESULTS: Using a cut-off value determined by analysis of H. pylori-negative Australian samples, the sensitivity, specificity and accuracy of the IgG2 assay were 77.8, 97.4 and 91.1%, respectively, for the Australian samples and 96.3, 83.8 and 90% for Hong Kong samples. For the IgG assay, sensitivity, specificity and accuracy were 87.0, 99.1 and 95.2% for Australian samples and 97.5, 75 and 86.3% for Hong Kong samples respectively. Receiver-operating characteristic analysis showed better discrimination of H. pylori status when the IgG2 assay was applied to Hong Kong samples, while the IgG assay was better in the Australian samples. CONCLUSION: These data demonstrate that the Helirad Alert enzyme-linked immunoassay could provide a reliable method for screening H. pylori infection in both western and Chinese populations.

Adult↗

gammadelta T cells increase with gastric mucosal interleukin (IL)-7, IL-1beta, and Helicobacter pylori urease specific immunoglobulin levels via CCR2 upregulation in Helicobacter pylori gastritis.

BACKGROUND AND AIMS: The purpose of this study was to investigate possible factors that could impact on gammadelta T cell accumulation in the gastric mucosa. METHOD: Subjects were 22 Helicobacter pylori (H. pylori)-free and 75 H. pylori-infected mucosa biopsies classified into grades I approximately III gastritis as per our previous study. The number of gammadelta- and 45 RO-positive T cells were determined by immunostaining. Gastric mucosal anti-H. pylori urease specific antibodies and interleukin (IL)-1beta, IL-2, 4, 7, 10 and IL-12 levels were assayed by enzyme-linked immunosorbent assay (ELISA). CC chemokine receptor 2 (CCR2) expression levels, migration, and cytokine production in gammadelta T cells stimulated by H. pylori urease were also evaluated. RESULTS: The gammadelta T cell count was significantly higher in grade III gastritis which exhibits strong immunoglobulin (Ig)A and IgG responses to H. pylori urease with lymphoid follicles than in other groups. gammadelta T cell count was significantly correlated with IL-1beta and interleukin-7 (IL-7) levels in the gastric mucosa. H. pylori urease immunoreactivity was detected in lamina propria of grade III gastritis, along with many gammadelta T cells. After H. pylori eradication therapy, the gammadelta T cell count in grade III gastritis significantly decreased. H. pylori urease stimulated significant increases in CCR2 expression levels, although to a lesser degree than those induced by IL-7 stimulation in both peripheral and mucosal gammadelta T cells. Interferon (IFN)-gamma and IL-10 production was also stimulated by H. pylori urease in peripheral gammadelta T cells. CONCLUSIONS: Gastric mucosal increases in IL-7 and IL-1beta closely corresponded to the accumulation of gammadelta T cells in gastric mucosa. An association was also seen between gammadelta T cell accumulation and H. pylori urease-specific Ig levels.

Adult↗

Is the only good Helicobacter a dead Helicobacter?

BACKGROUND: Vast numbers of therapeutic studies of various drug regimens used for the cure of H. pylori infection have been published. However, many of these studies have been uncontrolled, included small numbers of patients, were published only as abstracts, differed widely in dosage sizes, schedules and durations and were of insufficient statistical power to make meaningful statements concerning their efficacy. Furthermore, there are no clear or universally accepted guidelines for the treatment of H. pylori infection. Thus, there remains profound confusion among practitioners on whom and how to treat. OBJECTIVE: To critically review the currently available management strategies for H. pylori infection. METHODS: Review of the literature. RESULTS: Treatment of H. pylori requires the use of multiple drug regimens (triple therapy) which can be expensive and is often associated with side effects. Bad choice of treatments, poor patient counseling and compliance will lead to the emergence of resistant H. pylori strains. Resistance to H. pylori to metronidazole is already widespread and resistance to other antimicrobial agents is increasing. The resource/financial implications are not negligible. CONCLUSIONS: The introduction of kits that will enable the identification of pathogenic strains of H. pylori in the office setting may decrease the number of patients being given H. pylori eradication therapy, but much more evidence is needed to establish the practical value of such tests. In the meantime, as many clinicians adhere to the idea that the only good H. pylori is a dead H. pylori, the best practical policy option is education concerning the correct diagnostic methodology, correct choice of patients and the correct choice of treatment regimens. The discovery of Helicobacter pylori (H. pylori) has revolutionized our concepts of etiology, pathophysiology and treatment of many foregut diseases. Gastritis, gastric ulcer (GU), duodenal ulcer (DU), gastric cancer, MALT gastric lymphoma and other conditions are now regarded as being independent on the colonization of the stomach by H. pylori. Many aspects of pathophysiology, such as the abnormalities of gastric acid secretion in duodenal ulcer disease, now for the first time fall into a logical and comprehensible pattern.

Anti-Bacterial Agents↗

Anti-Helicobacter pylori specific antibody immunohistochemistry improves the diagnostic accuracy of Helicobacter pylori in biopsy specimen from patients treated with triple therapy.

OBJECTIVE: To investigate the effectiveness of immunohistochemical technique to detect Helicobacter pylori (H. pylori) in patients treated with triple therapy. METHODS: Forty patients (18 men, 22 women, mean age 43 years) with active antral gastritis, H. pylori positive at urease test, culture, and histology, were treated for 1 wk with omeprazole, amoxicillin, and metronidazole. Gastritis was scored according to Sydney criteria. Two months after the end of therapy, endoscopy, urease test, culture, and histology were repeated. RESULTS: Culture and histology were negative in 32 (80%) of treated cases. Biopsy specimens of the eradicated group were stained with immunohistochemical technique using an anti-H. pylori specific polyclonal antibody. In 12 of 32 (37.5%) patients, clusters of round or vibrio-shaped bacteria, unidentified at histology, were stained by the specific anti-H. pylori antibody. After triple therapy, at histology all patients were found with improved gastritis. In six patients however, mucosal-associated lymphoid tissue (MALT) appearance, present before therapy, persisted after therapy. In five of six patients with MALT, immunostaining with anti-H. pylori antibody was positive. CONCLUSIONS: The immunohistochemical technique is more accurate than classical methods in identifying H. pylori after specific therapy. This method should, therefore, be used in all studies that aim to achieve eradication. Whether the H. pylori identified at immunohistochemistry is able to reactivate and induce recrudescence of infection remains to be clarified.

Adult↗

Noninvasive antigen-based assay for assessing Helicobacter pylori eradication: a European multicenter study. The European Helicobacter pylori HpSA Study Group.

OBJECTIVE: In a recently published multicenter study involving 501 patients undergoing esophagogastroduodenoscopy (EGD) throughout Europe, we showed the high accuracy of a recently developed simple test (HpSA) to detect Helicobacter pylori (H. pylori) antigens in stools of untreated patients. The aim of this study was to assess the diagnostic usefulness of HpSA compared with 13C UBT shortly after H. pylori eradication treatment. METHODS: Of the 501 patients enrolled in the validation study, 279 were found to be H. pylori-positive. These patients were given H. pylori eradicating regimen and asked to return for follow-up EGD with biopsies, 13C UBT and HpSA testing 4 wk after therapy. Follow-up results were available for 235 patients. Of these, 162 consented to all testing and 73 consented only to 13C UBT and HpSA testing. We assessed sensitivity and specificity of both HpSA and 13C UBT compared with biopsy-based methods in the 162 patients, who accepted follow-up EGD. We also assessed sensitivity and specificity of HpSA compared with 13C UBT, arbitrarily chosen as the gold standard, in the whole population of 235 patients. RESULTS: Sensitivity and specificity in 162 patients who consented to a second EGD were 93.8% (CI: 85.4-100%) and 96.9% (CI: 93.9-99.9%) for HpSA, and 90.6% (CI: 80.5-100%) and 99.2% (CI: 97.7-100%) for UBT. Using EGD-based methods as the gold standard, 130 of the 162 treated patients' H. pylori infection were eradicated (125 HpSA-negative, one borderline, and four false-positive; 129 13C UBT-negative, one false-positive), and 32 remained H. pylori-infected (30 HpSA-positive, two false-negative, 29 13C UBT-positive, three false negative). The overall eradication rate was 80.2%. The sensitivity and specificity of HpSA relative to UBT as the gold standard in the overall population (n = 235) were 95.6% (CI: 89.6-100%) and 94.7% (CI: 91.5-97.9%), respectively. CONCLUSIONS: HpSA has proven to be a useful method in posttreatment eradication testing for H. pylori. Its ease of use, speed, and noninvasive nature make HpSA testing an ideal method for post-treatment monitoring where a second EGD may not be justified.

Adult↗

Evaluation of the Helicobacter pylori stool antigen test (HpSA) for detection of Helicobacter pylori infection in children.

OBJECTIVE: Helicobacter pylori (H. pylori) infection is usually acquired in early childhood. Noninvasive methods for detection of H. pylori infection are required to study its incidence, transmission, and clearance. They should be easy to perform, inexpensive, and have a high diagnostic accuracy, especially in infants and toddlers. Both serology and the 13C-urea breath test (13C-UBT) do not fulfill all these requirements. The aim of this study was to evaluate a new enzyme immunoassay for detection of H. pylori antigen in stool (Premier Platinum HpSA, Meridian Diagnostics, Cincinnati, OH) in a large cohort of children and to compare it to invasive techniques and the 13C-UBT. METHODS: HpSA was performed in 310 stool samples of 274 children divided into three groups. Group A consisted of 145 children and adolescents (0.5-19.8 yr, 66/145 <6 yr) who underwent upper endoscopy for various gastrointestinal symptoms. H. pylori status was defined by histology, culture, and rapid urease test from biopsies of the antrum and corpus. A 13C-UBT was performed in 133 of 145 children. Group B consisted of 22 patients (5.7-16.1 yr) who were retested with both noninvasive tests 8 wk after anti-H. pylori triple therapy. Group C consisted of 129 healthy infants and toddlers (0.9-3.1 yr) who were tested with the 13C-UBT. Children with discrepant or positive test results were retested after 2 and 12 months. Results of the HpSA were read at 450/620 nm by spectrophotometry. An optical density <0.100 was defined as negative, >0.120 as positive, and values between 0.100 and 0.120 were considered as equivocal. RESULTS: In Group A, the HpSA gave false-negative results in five of 45 infected children and false-positive results in four of 100 noninfected children, whereas four patients (2.8%) showed equivocal results. In both infected and noninfected children, no relation between the optical density values and age was found. The 13C-UBT was correct in 132 of 133 children tested. In Group B, there was complete concordance between the HpSA and 13C-UBT: 19 children tested negative and three positive. In Group C, concordant results between the two noninvasive methods were found in 124 of 129 (96%) toddlers (122 negative and two positive). Retesting of five children with discrepant results revealed that, on initial testing, the HpSA was incorrect in two (one false-positive, one false-negative), and the 13C-UBT was incorrect in three (always false-positive). CONCLUSIONS: In symptomatic children, the HpSA revealed a sensitivity of 88.9% (95% CI 77.3-96.3) and a specificity of 94.0% (88.1-97.7) compared to the 13C-UBT, 100% (94.0-100) and 98.9% (94.7-100), respectively. However, in healthy toddlers, the HpSA performed as well as the 13C-UBT with excellent concordance between the two noninvasive tests. There was no age dependency of the stool test results, and changing the cutoff would not have improved accuracy. Thus, the HpSA test seems suitable to monitor the success of anti-H. pylori therapy.

Adolescent↗