Absence of benefit of eradicating Helicobacter pylori in patients with nonulcer dyspepsia.

BACKGROUND: The relation between Helicobacter pylori infection and nonulcer dyspepsia is uncertain. We tested the hypothesis that curing the infection will relieve symptoms of dyspepsia. METHODS: We randomly assigned 170 H. pylori-infected patients with nonulcer dyspepsia to receive twice-daily treatment with 20 mg of omeprazole, 1000 mg of amoxicillin, and 500 mg of clarithromycin for 14 days and 167 such patients to receive identical-appearing placebos; all patients were then followed through regular visits for 12 months. Symptoms were scored on diary cards for seven days before each visit. A carbon-13 urea breath test was performed at base line and repeated at 1 and 12 months, and endoscopic biopsy was performed at 12 months to determine H. pylori status. Treatment was considered successful if the patient had only mild pain or discomfort or none at all. RESULTS: The rate of eradication of H. pylori infection was 90 percent in the active-treatment group and 2 percent in the placebo group at four to six weeks (P<0.001). At 12 months, there was no significant difference between groups in the rate of successful treatment (46 percent in the active-treatment group and 50 percent in the placebo group; relative likelihood of success with active treatment, 0.93; 95 percent confidence interval, 0.73 to 1.18; P=0.56). There was also no significant difference in the rate of successful treatment at 12 months between patients who were H. pylori-negative and those who were H. pylori-positive (48 percent vs. 49 percent). The rates of successful treatment were also similar when patients were analyzed according to the type of dyspepsia (ulcer-like, reflux-like, or dysmotility-like) and changes in the quality of life. There was no significant association between treatment success and histologic improvement in chronic gastritis at 12 months (P=0.68). CONCLUSIONS: We found no evidence that curing H. pylori infection in patients with nonulcer dyspepsia leads to relief of symptoms.     

Metronidazole-resistant Helicobacter pylori is more prevalent in patients with nonulcer dyspepsia than in peptic ulcer patients in a multiethnic Asian population

The trend of increasing prevalence of antibiotic resistance among Helicobacter pylori strains has been suggested as a cause of the failure of treatment of H. pylori infections. In this study, 120 of 211 antral biopsy specimens from patients with dyspeptic symptoms were found to harbor H. pylori. The isolates from the 120 specimens were tested by the agar dilution method, and 38 (31.7%) were found to be metronidazole resistant. Among the 211 subjects, 81 of 115 (70.4%) patients with peptic ulcer (PU) were infected with H. pylori, whereas 39 of 96 (40.6%) patients with nonulcer dyspepsia (NUD) were infected with H. pylori. Interestingly, significantly more NUD patients than PU patients harbored metronidazole-resistant H. pylori (22 of 39 [56.4%] and 16 of 81 [19.8%], respectively; P < 0.001). A similar pattern was also observed among NUD patients of different ethnicities but not between male and female patients (23 of 78 [29.5%] and 15 of 42 [35.7%], respectively; P = 0.54). In the posttreatment follow-up, five of six patients who had positive urea breath test results, indicating treatment failure, were NUD patients. Of these, four harbored metronidazole-resistant H. pylori strains. This further illustrates the relevance of metronidazole-resistant H. pylori in NUD patients. The significantly higher percentage of metronidazole-resistant H. pylori isolates in NUD patients may be attributed to the protection offered by the mucus layer of the nonulcerated stomach to the bacteria that reside below it, resulting in organism exposure to sublethal concentrations of metronidazole and leading to the induction of metronidazole resistance. The results demonstrate that the H. pylori isolates colonizing NUD patients are more likely to be resistant to metronidazole. It will therefore be useful to reevaluate the use of metronidazole in the treatment of NUD patients infected with H. pylori.     

Efficacy of two triple eradication regimens in children with Helicobacter pylori infection

Triple therapy with bismuth subsalicylate, amoxicillin, metronidazole (BAM) or with omeprazole, amoxicillin, clarithromycin (OAC) has been commonly used for the eradication of Helicobacter pylori infection. We compared the efficacy of these triple therapies in children with H. pylori infection. We retrospectively analyzed results in 233 children with H. pylori infection and treated with OAC (n=141) or BAM (n=92). Overall eradication rates of triple therapy with OAC and BAM were 74% and 85%, respectively, which showed no statistical difference. Our study showed that the triple therapy with BAM was more effective for the first-line eradication of H. pylori infection in Korean children, but has no statistical difference with OAC regimen.     

Effect of Helicobacter pylori eradication in Iranian patients with functional dyspepsia: a prospective,randomized, placebo-controlled trial

Introduction

Whether patients with functional dyspepsia (FD) should receive Helicobacter pylori (H. pylori) eradication therapy remains controversial. The objective of this trial was to evaluate the effect of H. pylori eradication therapy on dyspeptic symptoms of patients with FD.

Material and methods

A prospective, randomized, placebo-controlled trial of H. pylori eradication for FD was conducted. A total of 720 FD patients diagnosed by Rome III criteria were consecutively enrolled. We randomly assigned 186 H. pylori infected patients with FD to receive quadruple therapy for 14 days and 173 such patients to receive identical-appearing placebos. Severity of abdominal symptoms was assessed with the Glasgow Dyspepsia Severity Score (GDSS), and eradication of H. pylori by ¹³C-urea breath test was evaluated during one year.

Results

The rate of eradication of H. pylori infection was 87.1% in the treatment group and 2.9% in the placebo group at 6 weeks (p = 0.001). The mean GDSS at 12 months was 4.9 ±2.8 in the treatment group, as compared to 5.2 ±3.4 in the placebo group (p = 0.064). The scores in both groups were lower than those at baseline. According to the intention-to-treat analysis, at 12 months, there was no significant difference between groups in the rate of successful treatment (48.6% in the treatment group and 51.2% in the placebo group; p = 0.84). There was no significant difference in mean symptom scores between the two treatment groups at any point during follow-up.

Conclusions

The results of our study provide no evidence that H. pylori eradication leads to relief of symptoms 12 months after treatment, and there is a need for further studies.     

Distribution of vacA alleles and cagA status of Helicobacter pylori in peptic ulcer disease and non-ulcer dyspepsia

The occurrence of cagA and vacA alleles among Helicobacter pylori isolates from Turkish patients and their relationship with ulcer disease outcome was investigated. Among isolates from 47 patients with peptic ulcer disease and 51 patients with non-ulcer dyspepsia, 72.3% and 44.4%, respectively, were cagA-positive (p 0.019). Most (88.8%) isolates were typed as vacA s1, and all of these were subtype s1a. The commonest (51.0%) vacA genotype was s1a m1. The results of multivariate analysis indicated that infection with cagA-positive H. pylori was the only variable associated with an increased risk of peptic ulcer disease (odds ratio, 3.01; 95% confidence interval, 1.27-7.10; p 0.012).     

Polymorphisms of Helicobacter pylori HP0638 Reflect Geographic Origin and Correlate with cagA Status

Since the associations between Helicobacter pylori genotype and disease differ in Asia and the West, we investigated the correlation between HP0638, encoding an outer membrane protein, and potential markers of virulence (cagA, vacA, and iceA). For 109 strains from nine countries, the status of cagA, vacA, and iceA was determined by PCR and/or a line probe assay. We also studied 18 strains from 8 patients (parents and 6 daughters) from a Dutch family and paired strains collected on average 8 years apart from 11 patients. When the HP0638 signal sequences were amplified by PCR and DNA sequence determinations were performed, 89 (96%) of 93 cagA-positive strains had HP0638 in frame, versus none (0%) of 16 cagA-negative strains (P < 0.001). Among strains in which HP0638 was in frame, a six-CT dinucleotide repeat pattern was dominant in Western countries (23 of 33 strains [70%]), while a pattern of three CT repeats with another CT after four T's (3 + 1-CT-repeat pattern) was dominant in East Asia (31 of 46 strains [67%]); however, specific CT repeat patterns did not correlate with clinical outcome. HP0638 phylogenetic trees also showed geographic characters. The HP0638 frame status and CT dinucleotide repeat patterns were identical for 9 of 11 pairs of strains obtained on average 8 years apart from individuals and the 15 strains obtained from the mother and all six daughters. Thus, HP0638 frame status and cagA status are strongly correlated. The CT dinucleotide repeat pattern in the putative HP0638 signal sequence has geographic characters and appears stable in particular patients and families over a period of years. Analysis of HP0638 CT polymorphisms may serve as a new typing system to discriminate H. pylori isolates for epidemiological purposes.     

Histological and immunological parameters to predict treatment outcome of Helicobacter pylori eradication in low-grade gastric MALT lymphoma

Helicobacter pylori eradication is generally accepted as the first choice of treatment for stage IE low-grade gastric MALT lymphoma (mucosa-associated lymphoid tissue-type lymphoma). Treatment failure may be attributed to the extent of the disease and to progression into an antigen-independent phase. This study assessed the value of morphological grading and the expression of the co-stimulatory markers CD40, CD80 and CD86 and their ligands to predict clinical outcome in 23 consecutive low-grade MALT lymphoma patients treated with H. pylori eradication. Complete regression was achieved in 13/23 patients (56%), partial regression in two (9%), and no response in eight (35%). Histological grading was highly predictive of clinical response, especially in stage IE(1) patients, with complete remissions in 10/12 tumours with purely low-grade (type A) morphology and 1/8 tumours with increased numbers of blasts (type B) (p=0.0046) and was related to the expression of costimulatory markers (p=0.0061). Moreover, CD86 as a single marker proved to be of predictive value for treatment outcome (p=0.0086). These results suggest that morphological grading and immunological criteria can be defined to recognize the transition into the antigen-independent phase of gastric MALT-NHL. In addition to clinical stage, these critera may in future serve as a practical pathological guide to the choice of therapy.     

Prevalence of Helicobacter pylori vacA and cagA genotypes in Ethiopian dyspeptic patients

A total of 300 gastric biopsy samples and 50 Helicobacter pylori isolates were collected from Ethiopian adult dyspeptic patients. The vacA and cagA genes were detected in 90 and 79% of biopsy specimens, respectively, and in 100 and 87% of clinical isolates, respectively. Both genes were detected in 84% of the gastric biopsy samples and in 87% of the clinical isolates. Among vacA genotypes, the s1/m1 genotype was the most common in gastric biopsy samples (48%). The vacA and cagA positive H. pylori strains were detected to a higher degree in patients with chronic active gastritis (71%) than patients with other histopathological findings (29%) (P < 0.05).     

Personalized treatment in the eradication therapy for Helicobacter pylori

Helicobacter pylori (HP) is known to be a causative bacterium of gastritis and peptic ulcers. The combination treatment consisting of a proton pump inhibitor (PPI), amoxicillin and clarithromycin (CAM) is widely used in eradication therapy, but the eradication fails in some patients. The main causes are CAM resistance of HP and individual variability in PPI metabolism related to the activity of the cytochrome P450 2C19 (CYP2C19) enzyme. In this study, we examined the usefulness of the prediction of the pharmacotherapeutic efficacy using a newly developed analysis system for HP CAM resistance and CYP2C19 genotypes. After obtaining the informed consent from 45 subjects with HP-positive peptic ulcers, biopsy specimens of the gastric mucosa were obtained by endoscopy. HP DNA extracted from the gastric mucosa was examined by the SELMAP-PCR method, the direct sequencing method or the single-nucleotide primer extension (SNuPE) method. HP detection rates by culture and the SELMAP-PCR method were 71% and 100%, respectively. Among 32 cultured HP, CAM resistance was confirmed in 6 samples by the in vitro drug susceptibility test. CAM-resistant gene mutations were also examined by the SELMAP-PCR method using 32 DNAs from cultured HP and the results were consistent with the drug susceptibility test. Among 22 patients, the eradication rate was 77%. Among 4 patients with CAM resistance determined by both the in vitro drug susceptibility test and the SNuPE method, eradication was successful in one intermediate metabolizer (IM), but not in three extensive metabolizers (EMs). Patients were divided into three groups according to their CYP2C19 phenotype: EMs, IMs and poor metabolizers (PMs). The eradication rates for 6 EMs, 12 IMs and 4 PMs were 33.3%, 91.7% and 100%, respectively. Based on these results, the information on CAM resistance in HP and CYP2C19 phenotypes in carriers could predict the pharmacotherapeutic efficacy and probability of eradication. It can then be possible to vary the dosing or to select another drug by the prediction of the pharmacotherapeutic efficacy.     

Prevalence of Helicobacter pylori vacA,cagA and iceA genotypes in Nigerian patients with duodenal ulcer disease

Distinct virulence factors of Helicobacter pylori have been associated with clinical outcome of the infection; however, considerable variations have been reported from different geographic regions. Data on genotypes of African H. pylori isolates are sparse. The aim of this study was to determine the prevalence of specific genotypes of H. pylori in Nigerian patients with duodenal ulcer and non-ulcer dyspepsia. H. pylori was cultured from endoscopic biopsies obtained from 41 Nigerian patients (19 with duodenal ulcer, 22 with non-ulcer dyspepsia). The vacA alleles, cagA and iceA genotypes were determined by PCR. The vacA s1,m1 and s1,m2 genotypes were found in 26.3% and 22.7%, and in 73.7% and 72.7% of H. pylori isolates from patients with duodenal ulcer and non-ulcer dyspepsia, respectively. The iceA1 genotype was present in 94.7% and 86.4% of isolates from duodenal ulcer and non-ulcer dyspepsia patients, respectively. cagA+ infection was found predominantly (> 90%) in Nigerian H. pylori isolates irrespective of the clinical diagnosis. In conclusion, vacA s1,m2, iceA1 and cagA+ are common genotypes of H. pylori isolated from Nigerian patients. As in several other developing countries there seems to be no association between these genotypes and duodenal ulcer disease.     

The prevalence of anti-Helicobacter (Campylobacter) pylori antibodies in patients and healthy blood donors

An enzyme linked immunosorbent assay (ELISA) with a sonicated suspension of Helicobacter (Campylobacter) pylori as antigen was used to detect anti-H. pylori antibodies in 517 patients without dyspepsia or peptic ulcer symptoms and 401 healthy blood donors. The criterion of seropositivity was determined from a receiver operating curve computed with the values of optical densities of 48 sera from dyspeptic patients with proven helicobacter-associated gastritis and 16 sera from dyspeptic patients with normal antral mucosa and no microbiological or histological evidence of H. pylori infection. The 227 (44%) seropositive persons amongst the patient group appeared to be significantly higher than the 142 (35%) sera with antibodies in the blood donors tested (p less than 0.03), even when adjustment was made for increasing age. We conclude that the prevalence of antibodies against H. pylori increases with age and that although antibodies are more prevalent in patients attending a hospital than in healthy blood donors, seropositivity suggestive of current or past infection can be found in one third of a randomly chosen population of blood donors.     

The effect of Helicobacter pylori eradication on proteinuria in patients with primary glomerulonephritis

Introduction

Glomerulonephritis is still the primary cause among the diseases causing end stage renal disease. Helicobacter pylori (HP), also having a local proinflammatory effect on gastric mucosa, can trigger a local and systemic inflammatory response, and consequently have a role in the development of extragastrointestinal defects.

Material and methods

The study was composed of patients diagnosed with primary glomerulonephritis who had dyspeptic complaints throughout the diagnosis. Patients who received endoscopic biopsy upon the determination of pathologic findings in their upper gastrointestinal endoscopy were HP positive in their biopsy material. A triple eradication therapy was initiated for HP.

Results

The study included 14 female and 19 male patients, 33 in total, whose biopsy material was determined to be HP positive. Before the eradication for HP, we found serum albumin to be 34.0 (19.0–51.0) g/l, serum total protein 58.6 ±12.9 g/l, serum creatinine 0.9 (0.5–1.2) and proteinuria 3069 (652–12392) mg/day in 24-hour urine. After the eradication, however, serum albumin was found to be 40 (20–52) g/l, serum total protein 62.3 ±11.1 g/l, serum creatinine 1.02 (0.6–1.29) mg/dl and proteinuria was 2850 (172–15181) mg/day in 24-hour urine. A comparison of the results showed that a statistically significant difference is established between the serum albumin, total protein and creatinine values (p = 0.001, p = 0.001 and p = 0.021, respectively), but not between proteinuria values in 24-hour urine (p = 0.990).

Conclusions

Patients with primary glomerulonephritis, HP eradication treatment has an effect on serum albumin levels.     

Insulin-like growth factor-I in Helicobacter pylori gastritis and response to eradication using bismuth based triple therapy.

AIMS: To measure insulin-like growth factor-I (IGF-I) concentrations in the presence and absence of Helicobacter pylori infection and in response to eradication of the organism. METHODS: An enzyme linked immunosorbent assay was used to measure gastric and fasting serum concentrations of IGF-I in 17 patients with and 11 without H pylori infection. Repeat assessments were performed in the infected patients six weeks after they received a two week course of bismuth chelate, metronidazole, and amoxycillin. RESULTS: IGF-I was detected at very low concentrations in gastric juice and in mucosal incubates. The median serum IGF-I concentration was 88 micrograms/l in the patients infected with H pylori compared with 90 micrograms/l in the non-infected controls; IGF-I concentrations dropped to 77 micrograms/l following eradication therapy (p = 0.014). CONCLUSION: The similarity in baseline IGF-I concentrations in the presence and absence of H pylori suggests that their subsequent drop after treatment is more likely to be due to the treatment.     

The cause of failure of eradication treatment of Helicobacter pylori

The drug treatment, the combination of lansoprazole + amoxicillin + clarithromycin, for Helicobacter pylori infection with gastroduodenal ulcer was approved for the national heath insurance November 2000 in JAPAN, and has been widely applied. However, failures of eradication have been counted in 10-20% of the cases. The major reason of the failure has been reported as the drug resistance of the H. pylori. Here, we surveyed the antimicrobial resistance of 70 clinical isolates in a Showa University Hospital 2001, 1 to 2002, 1. As a result, the ratio of primary resistance to amoxicillin was about 1.4%, and clarithromycin was about 11.4%. Among 70 H. pylori positive cases, 14 cases were treated with eradication 3 drug combination therapy. In 5 cases, H. pylori were detected after eradication treatment and these five strains acquired the second resistance to neither amoxicillin nor clarithromycin. To distinguish the cause of H. pylori culture-positive after eradication treatment is whether the failure of eradication itself or re-infection, we attempted the analysis of the restriction pattern of H. pylori genome (genome type) using pulsed-field gel electrophoresis. In all 5 cases, genome types of before and after treatment were identical, suggesting the failure of eradication treatment. Three of 5 cases, isolates before and after treatment were susceptible to both of amoxicillin and clarithromycin. Thus, the reason of failure of eradication is considered to ingestion compliance, not antimicrobial agent resistance nor reinfection. The rest of 2 cases, the primary resistance to clarithromycin may result the failure of eradication. Test for drug susceptibility and genome type analysis of H. pylori are significant in certification of an authenticity of an eradication treatment.     

Clinical relevance of cagA and vacA gene polymorphisms in Helicobacter pylori isolates from Senegalese patients

The molecular epidemiology of Helicobacter pylori in Africa is poorly documented. From January 2007 to December 2008, we investigated 187 patients with gastric symptoms in one of the main tertiary hospitals in Dakar, Senegal. One hundred and seventeen patients were culture-positive for H. pylori. Polymorphisms in vacA and cagA status were investigated by PCR; the 3′-region of cagA was sequenced, and EPIYA motifs were identified. Bacterial heterogeneity within individuals was extensively assessed by using an approach based on vacA and cagA heterogeneity. Fourteen per cent of H. pylori-positive patients displayed evidence of mixed infection, which may affect disease outcome. Patients with multiple vacA alleles were excluded from subsequent analyses. Among the final study population of 105 patients, 29 had gastritis only, 61 had ulcerated lesions, and 15 had suspicion of neoplasia based on endoscopic findings. All cases of suspected neoplasia were histologically confirmed as gastric cancer (GC). The cagA gene was present in 73.3% of isolates. CagA proteins contained zero (3.7%), one (93.9%) or two (2.4%) EPIYA-C segments, and all were western CagA. Most of the isolates possessed presumed high-vacuolization isotypes (s1i1m1 (57.1%) or s1i1m2 (21.9%)). Despite the small number of cases, GC was associated with cagA (p 0.03), two EPIYA-C segments in the C-terminal region of CagA (p 0.03), and the s1 vacA allele (p 0.002). Multiple EPIYA-C segments were less frequent than reported in other countries, possibly contributing to the low incidence of GC in Senegal.     

Relationship between bacterial load,morbidity and cagA gene in patients infected by Helicobacter pylori

One hundred and seventy-six biopsies of the gastric corpus and antrum from 97 patients were processed using classical and molecular methods in order to study the relationship between the factor cagA of Helicobacter pylori, bacterial load and morbidity. Bacterial load in patients with cagA was greater than in patients without it, both in the antrum and corpus (p < 0.01). There was a statistically significant association between cagA and consumption of proton pump inhibitors (adjusted odds ratio 3.11). Haemorrhage of the upper digestive tract was more associated with bacterial load than with the cagA gene (adjusted odds ratio 2.34 and 1.12, respectively), but none of these associations yielded statistical significance.