European Registry on Helicobacter pylori management (Hp-EuReg): patterns and trends in first-line empirical eradication prescription and outcomes of 5 years and 21 533 patients.

OBJECTIVE: The best approach for Helicobacter pylori management remains unclear. An audit process is essential to ensure clinical practice is aligned with best standards of care. DESIGN: International multicentre prospective non-interventional registry starting in 2013 aimed to evaluate the decisions and outcomes in H. pylori management by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables included demographics, previous eradication attempts, prescribed treatment, adverse events and outcomes. Data monitoring was performed to ensure data quality. Time-trend and geographical analyses were performed. RESULTS: 30 394 patients from 27 European countries were evaluated and 21 533 (78%) first-line empirical H. pylori treatments were included for analysis. Pretreatment resistance rates were 23% to clarithromycin, 32% to metronidazole and 13% to both. Triple therapy with amoxicillin and clarithromycin was most commonly prescribed (39%), achieving 81.5% modified intention-to-treat eradication rate. Over 90% eradication was obtained only with 10-day bismuth quadruple or 14-day concomitant treatments. Longer treatment duration, higher acid inhibition and compliance were associated with higher eradication rates. Time-trend analysis showed a region-dependent shift in prescriptions including abandoning triple therapies, using higher acid-inhibition and longer treatments, which was associated with an overall effectiveness increase (84%-90%). CONCLUSION: Management of H. pylori infection by European gastroenterologists is heterogeneous, suboptimal and discrepant with current recommendations. Only quadruple therapies lasting at least 10 days are able to achieve over 90% eradication rates. European recommendations are being slowly and heterogeneously incorporated into routine clinical practice, which was associated with a corresponding increase in effectiveness.

Role of earlier gastroscopy in predicting findings on repeat gastroscopy in a population with a low H. pylori prevalence.

OBJECTIVE: Repeat gastroscopy is not recommended for patients without alarm symptoms and with a normal earlier gastroscopy. However, there is little information available on the consequences of this recommendation. The objective of this study was to examine the role of earlier gastroscopy results in predicting the findings at repeat gastroscopy. MATERIAL AND METHODS: Patients with previous gastroscopies presenting for a new gastroscopy during 2004-05 were included consecutively. A total of 293 patients who had undergone a gastroscopy a mean of 7.7 years (range 0.6-25.4 years) before the present gastroscopy were included in the study. The patients completed a questionnaire. The associations between the findings of the present gastroscopy and the findings of the previous gastroscopy and other patient characteristics were analysed by stepwise logistic regression. RESULTS: Nine percent of the patients were positive for Helicobacter pylori infection. An abnormal macroscopic finding, defined as any erosion, ulcer or other macroscopic finding with the exception of hiatus hernia, at the repeat gastroscopy was significantly positively associated with: 1) an abnormal finding at a previous gastroscopy (OR 2.94, 95% CI 1.48-5.85), 2) obesity (body mass index, BMI >30) (OR 2.89, 95% CI 1.28-6.55), 3) the presence of alarm symptoms (OR 2.68, 95% CI 1.29-5.56), and negatively associated with 4) the use of proton pump inhibitors (OR 0.48, 95% CI 0.24-0.98). The findings were not associated with age. CONCLUSIONS: Abnormal earlier gastroscopy findings, obesity and the presence of alarm symptoms were the strongest indicators of abnormal findings at repeat gastroscopy. Our results support a restrained gastroscopy policy in patients with no alarm symptoms and a normal earlier gastroscopy.

Irritable bowel syndrome symptom severity improves equally with probiotic and placebo.

AIM: To determine the effects of Lactobacillus acidophilus NCFM on irritable bowel syndrome (IBS) symptoms and quality of life (QoL). METHODS: In this randomized triple-blind trial, adult IBS volunteers who were recruited according to Rome III criteria received 109 or 1010 colony-forming units of NCFM or placebo daily for 12 wk. IBS Symptom Severity Score (IBS-SSS), which constituted the primary outcome, and secondary outcomes, including individual IBS symptoms, IBS-related QoL questionnaire, anxiety and depression, defecation frequency, and stool consistency, were assessed at baseline at the end of the 8-wk run-in period, after 4 and 12 wk of intervention, and after a 4-wk washout. RESULTS: A total of 340 of 391 randomized volunteers completed the trial. IBS-SSS improved over 12 wk of treatment in all treatment groups, decreasing by a mean ± SD of 44.0 ± 80.2, 50.8 ± 82.4, and 48.3 ± 72.2 in the placebo, active low-dose, and active high-dose groups, respectively. Similarly, secondary outcomes did not differ between treatment groups. However, in a post hoc analysis of volunteers with moderate to severe abdominal pain at baseline (VAS > 35/100), the treatment significantly reduced the sensation of abdominal pain. Pain scores fell by 20.8 ± 22.8, 29.4 ± 17.9, and 31.2 ± 21.9 in the placebo, active low-dose, and active high-dose groups, respectively (P value for placebo vs combined active doses = 0.0460). CONCLUSION: NCFM alleviates moderate to severe abdominal pain, consistent with earlier observations of this strain mitigating visceral pain through increased analgesic receptor expression.

Stool antigen tests in the diagnosis of Helicobacter pylori infection before and after eradication therapy.

AIM: To evaluate two enzyme immunoassay-based stool antigen tests, Premier Platinum HpSA and Amplified IDEIA HpStAR, and one rapid test, ImmunoCard STAT! HpSA, in the primary diagnosis of Helicobacter pylori (H pylori) infection and after eradication therapy. METHODS: Altogether 1 574 adult subjects were screened with a whole-blood H pylori antibody test and positive results were confirmed with locally validated serology and (13)C-urea breath test. All 185 subjects, confirmed to be H pylori positive, and 97 H pylori-negative individuals, randomly selected from the screened study population and with negative results in serology and UBT, were enrolled. After eradication therapy the results of 182 subjects were assessed. RESULTS: At baseline, the sensitivity of HpSA and HpStAR was 91.9% and 96.2%, respectively, and specificity was 95.9% for both tests. ImmunoCard had sensitivity of 93.0% but specificity of only 88.7%. After eradication therapy, HpSA and HpStAR had sensitivity of 81.3% and 100%, and specificity of 97.0% and 97.6%, respectively. ImmunoCard had sensitivity of 93.8% and specificity of 97.0%. HpSA, HpStAR, and ImmunoCard had PPV 77%, 80%, and 75%, and NPV 98%, 100%, and 99%, respectively. CONCLUSION: In primary diagnosis, the EIA-based tests performed well. After eradication therapy, negative results were highly accurate for all the three tests. HpStAR had the best overall performance.

Recent trends in primary antimicrobial resistance of Helicobacter pylori in Finland.

The antimicrobial susceptibility of Helicobacter pylori is an important predictor of the success of eradication therapy. To evaluate recent changes in primary antimicrobial resistance of H. pylori isolated from Finnish patients, the clinical records of H. pylori-positive patients referred for endoscopy to Herttoniemi Hospital (Helsinki, Finland) during 2000-2008 were investigated retrospectively. Stored H. pylori strains from 505 patients without previous eradication therapy were tested for clarithromycin, metronidazole, levofloxacin, tetracycline and amoxicillin susceptibility by Etest. Data on local consumption of antimicrobials were collected and correlations between consumption and resistance were calculated. During the 9-year study period, metronidazole resistance was high (range 29-59%, overall 41%). After an initial increase in clarithromycin resistance (0% in 2000 to 16% in 2003), resistance to clarithromycin decreased to 4% in 2008. No significant correlation was detected between consumption of macrolides and resistance of clarithromycin. Resistance to levofloxacin varied between 0% and 12%. Primary metronidazole resistance in H. pylori is at a high level, however levofloxacin and clarithromycin resistances are still at a reasonable level. Thus, primary clarithromycin resistance in H. pylori in Finland has not become such a problem as in many other countries. Primary resistance to the antimicrobials studied varied considerably from year to year.

Association of autoimmune type atrophic corpus gastritis with Helicobacter pylori infection.

AIM: To study the association between Helicobacter pylori (H. pylori) infection and autoimmune type atrophic gastritis. METHODS: Twenty-three patients with different grades of atrophic gastritis were analysed using enzyme immunoassay-based serology, immunoblot-based serology, and histology to reveal a past or a present H. pylori infection. In addition, serum markers for gastric atrophy (pepsinogen I, pepsinogen I/II and gastrin) and autoimmunity [parietal cell antibodies (PCA), and intrinsic factor (IF), antibodies] were determined. RESULTS: Of the 14 patients with severe gastric atrophy, as demonstrated by histology and serum markers, and no evidence for an ongoing H. pylori infection, eight showed H. pylori antibodies by immunoblotting. All eight had elevated PCA and 4/8 also had IF antibodies. Of the six immunoblot-negative patients with severe corpus atrophy, PCA and IF antibodies were detected in four. Among the patients with low to moderate grade atrophic gastritis (all except one with an ongoing H. pylori infection), serum markers for gastric atrophy and autoimmunity were seldom detected. However, one H. pylori negative patient with mild atrophic gastritis had PCA and IF antibodies suggestive of a pre-atrophic autoimmune gastritis. CONCLUSION: Signs of H. pylori infection in autoimmune gastritis, and positive autoimmune serum markers in H. pylori gastritis suggest an etiological role for H. pylori in autoimmune gastritis.

Enhanced systemic matrix metalloproteinase response in Helicobacter pylori gastritis.

BACKGROUND: Helicobacter pylori causes chronic gastritis, peptic ulcer disease, and is the most important risk factor for non-cardia gastric cancer, and has been shown to upregulate matrix metalloproteinases (MMPs) in infected gastric mucosa. MMPs are proteolytic enzymes regulated by tissue inhibitors of metalloproteinases (TIMPs). AIMS: We set up this study to find out whether H. pylori gastritis induces systemic MMP response. METHODS: Serum samples were collected from patients undergoing gastroscopy; 26 patients had H. pylori gastritis and 18 were H. pylori-negative controls with normal gastric mucosa. Serum MMP levels were analysed by enzyme-linked immunosorbent assay. RESULTS: Significantly elevated serum levels of collagenase-2 (MMP-8), gelatinase B (MMP-9), neutrophil elastase (NE), and myeloperoxidase (MPO), and reduced serum levels of gelatinase A (MMP-2) and TIMP-1 were demonstrated in patients with H. pylori gastritis as compared to H. pylori-negative controls. No significant differences were shown in serum matrilysin-1 (MMP-7) levels. CONCLUSIONS: For the first time, we show enhanced MMP-8 response in H. pylori infection together with other neutrophil degranulation products (MMP-9, MPO, NE). Elevated circulating neutrophil degranulation product levels in serum of H. pylori-positive patients reflect accelerated proteolysis and oxidative stress, and may contribute to extraintestinal sequelae, such as cardiovascular diseases.

Evaluation of a commercial immunoblot, Helicoblot 2.1, for diagnosis of Helicobacter pylori infection.

The best method to diagnose Helicobacter pylori infection in different clinical situations is controversial. The aim of the study was to assess the performance of a commercial immunoblot, Helicoblot 2.1. The study comprised 215 patients, who were grouped according to the presence of H. pylori infection (assessed by two gastroscopies including histology with a median interval of 7.1 years, enzyme immunoassay [EIA]-based serology, and history of previous H. pylori infections and eradication therapies) into four categories: no H. pylori infection ever, previous infection, ongoing infection, and EIA seropositivity as the only marker of a possible previous infection. The sensitivity of Helicoblot 2.1 to show an ongoing or previous H. pylori infection was 100% and 92%, respectively. Helicoblot 2.1 was negative in only 80% of individuals with no evidence of present or previous infection but in 96% of patients 50 years of age or younger. The current infection marker of the immunoblot was positive in 49% of patients with successful H. pylori eradication therapy. After successful eradication therapy, Helicoblot 2.1 sustained positive results in 87% of patients, and CagA positivity was detected in 87% of patients with follow-up samples for more than 10 years after therapy. Helicoblot 2.1 is a sensitive and, among patients of ages 50 years or younger, a specific test in the primary diagnosis of H. pylori infection. However, it does not discriminate between past and current infections. It can be used in epidemiological studies assessing the role of H. pylori in different late sequelae.

Persisting chronic gastritis and elevated Helicobacter pylori antibodies after successful eradication therapy.

AIM: The persistence of chronic inflammation in gastric mucosa and elevated Helicobacter pylori antibodies after successful eradication therapy are common findings in clinical practice. We studied their possible association with each other and disappearance in long-term follow up, as well as their possible connection with gastric atrophy. PATIENTS AND METHODS: The study population consisted of 108 dyspeptic patients with successful eradication therapy median 6.4 years earlier. The patients underwent gastroscopy, and biopsies from antrum and corpus were evaluated by an experienced pathologist. Serum samples collected from 77 patients were studied for H. pylori antibodies, parietal cell antibodies, as well as for pepsinogen I, pepsinogen II, and gastrin-17 levels. RESULTS: The prevalence of chronic gastric inflammation and elevated H. pylori antibodies after successful eradication therapy decreased by time, but still after 5 years, 17 of 51 (33%) subjects had elevated H. pylori antibodies and 14 of 68 (21%) had a mild inactive chronic inflammation in gastric mucosa. In patients with and without chronic inflammation in gastric mucosa, elevated H. pylori antibodies were detected in three of 10 (30%) and 14 of 41 (34%), elevated parietal cell antibodies in one of 10 (10%) and six of 41 (15%), low pepsinogen I in one of 10 (10%) and none of 41, and elevated gastrin-17 in three of 10 (30%) and six of 41 (15%), respectively. CONCLUSION: More than 5 years after successful H. pylori eradication therapy, mild persistent chronic inflammation may occur in gastric mucosa in up to one-fifth and elevated H. pylori antibodies even in one-third of patients, although these two are independent phenomena.

Detection of Helicobacter species in chronic liver disease and chronic inflammatory bowel disease.

AIM: To study the association between helicobacters and chronic liver diseases and chronic inflammatory bowel diseases. PATIENTS AND METHODS: Thirty-two patients with various chronic liver diseases and 137 patients with inflammatory bowel disease were enrolled. Antibodies to H. pylori, H. hepaticus, H. bilis, and H. pullorum were measured by enzyme immunoassay (EIA), and sera positive in a non-pylori helicobacter EIA were further examined by immunoblot assay. Detection of Helicobacter DNA in liver biopsies was done by denaturating gradient gel electrophoresis of PCR products (PCR-DGGE) and DNA sequence analysis. RESULTS: Six inflammatory bowel disease patients, four with ulcerative colitis and two with Crohn's disease, and one liver disease patient with autoimmune cholangitis had antibodies to non-pylori helicobacters by an immunoblot assay. Four immunoblot assay-negative patients, three with autoimmune and one with non-autoimmune liver disease, had Helicobacter DNA in liver biopsies; three of the polymerase chain reaction (PCR) products were closely related to non-pylori helicobacters. CONCLUSION: Evidence for non-pylori helicobacters was scant in Finnish patients with inflammatory bowel disease or chronic but not end stage liver disease. We cannot, however, rule out their role in these diseases.

Helicobacter pylori eradication in the healing of atrophic gastritis: a one-year prospective study.

OBJECTIVE: Whether gastric atrophy or intestinal metaplasia heals after successful treatment of Helicobacter pylori (H. pylori) infection is still a matter of controversy. The aim of this article was to clarify whether, after one year, H. pylori eradication is associated with healing in glandular atrophy and intestinal metaplasia in the corpus and antrum. MATERIAL AND METHODS: Ninety-two H. pylori-positive peptic ulcer patients with atrophic gastritis (panatrophy, antral or corpus predominant) participated in the baseline study, 1-year prospective follow-up data being available from 76 patients. Mean age was 58+/-12.6 years (mean+/-SD) and the male/female ratio 2/1. The patients participated in an H. pylori eradication study in which they randomly received active eradication therapy. Endoscopy was performed before H. pylori eradication therapy and after 8 and 52 weeks, with specimens examined according to the Sydney system. RESULTS: Of the 92 patients, 8 (9%) had panatrophy, 58 (63%) had antral- and 26 (28%) had corpus-predominant atrophic gastritis. After H. pylori eradication, the mean atrophy score declined in patients with antral-predominant atrophy from 1.5 (mean) to 0.7 (p<0.05), in corpus-predominant atrophy from 1.7 to 0.2 (p=NS) and in patients with panatrophy from 1.2 to 0.8 (p=NS). Atrophy healing was seen in 55% of antral-predominant atrophy patients who had successful H. pylori eradication. The mean antral atrophic score in one year declined in patients with duodenal ulcer (from 1.0 mean to 0.4) whereas it remained the same (1.3) in those with gastric ulcer (p<0.05). CONCLUSIONS: Atrophy can diminish or even disappear, especially in the antrum, during a 1-year follow-up after eradication of infection. Atrophy progression seems milder in patients with duodenal ulcer than in patients with gastric ulcer.

Clinical significance of widespread gastric metaplasia in the duodenal bulb.

BACKGROUND: All the risk factors of peptic ulcer disease are not thoroughly understood. GOALS: To assess duodenal gastric metaplasia (DGM) in relation to Helicobacter pylori status and endoscopy findings with special reference to the effects of highly selective vagotomy. STUDY: The study population consisted of 1056 adult patients and an additional 154 patients who had had a highly selective vagotomy. Their clinical and endoscopy records as well as the histology of gastric and duodenal biopsies were evaluated retrospectively. H. pylori infection had been determined by serology and culture. RESULTS: Widespread (more than 20%) DGM was strongly associated with H. pylori positive duodenal ulcer disease (in 59.7% of patients). The prevalence of DGM diminished progressively the more proximally the ulcer was located in the stomach, and was 2.5% in proximal gastric ulcers patients. In vagotomized patients, the prevalence of widespread DGM (8.4% of patients, median 14 years after operation and the majority still H. pylori positive) was close to that of patients with H. pylori gastritis without peptic ulcer disease (4.5%). CONCLUSIONS: Widespread DGM is an indicator for an increased risk of duodenal ulcer among H. pylori positive patients and it could be used to select patients for eradication therapy.

Comparison of three stool antigen tests in confirming Helicobacter pylori eradication in adults.

OBJECTIVE: Reliable and readily available non-invasive methods are needed for detection of Helicobacter pylori infection and assessment of eradication therapy. In H. pylori-positive subjects we compared three stool antigen tests (Premier Platinum HpSA, Amplified IDEIA HpStAR and ImmunoCard STAT!HpSA) with invasive tests before their eradication therapy, and with non-invasive diagnostic methods after their therapy. MATERIAL AND METHODS: A total of 82 adults with dyspepsia (aged 24-79 years) with an H. pylori-positive rapid urease test were enrolled in the study. Before therapy, H. pylori status was also confirmed with histology, culture and serology. After eradication, success was assessed with the [13C]-urea breath test (UBT) and usually also with serology. RESULTS: At baseline, sensitivities of these stool antigen tests were 90.2% for HpSA, 97.6% for HpStAR and 96.3% for ImmunoCard. Eradication therapy was successful in 66 patients and unsuccessful in 16. Sensitivity and specificity of the three stool antigen tests in the post-eradication setting were, respectively, 75.0% and 95.5% for HpSA, 93.8% and 98.5% for HpStAR and 87.5% and 95.5% for Immunocard. CONCLUSIONS: The performance of all three stool antigen tests in the post-treatment setting was slightly inferior to that of the UBT test and serology, with monoclonal antibody-based tests showing better results.