Helicobacter pylori and Non-malignant Diseases

It is well known that Helicobacter pylori infection is associated with many nonmalignant disorders such as gastritis, peptic ulcer, gastroesophageal reflux disease (GERD), gastric polyp, nonsteroidal anti-inflammatory drug (NSAID)/aspirin-induced gastric injury, and functional dyspepsia. In 2008, interesting articles on the association of H. pylori infection with these disorders were presented, some of which intended to reveal the mechanisms of inter-individual differences in response to H. pylori infection, and have demonstrated that genetic differences in host and bacterial factors as well as environmental factors account for these differences. A decline in the occurrence of peptic ulcer related to H. pylori was confirmed. An inverse relationship between H. pylori infection and GERD was also confirmed but the impact of gastric atrophy on the prevention of GERD remained debatable. For NSAID-induced gastric injury, eradication of H. pylori infection has been recommended. During this year, eradication of H. pylori infection was recommended for patients treated with antiplatelet therapy as well as aspirin and NSAID. It was also reported that for patients with functional dyspepsia, eradication of H. pylori offers a modest but significant benefit.     

Pilot studies to identify the optimum duration of concomitant Helicobacter pylori eradication therapy in Thailand

Background and Aim: Eradication rate for Helicobacter pylori infection with standard triple therapy has globally declined including in Thailand, and new regimens are required that provide reliable high eradication rates. The study was designed to determine whether concomitant therapy administered for either 5 or 10 days would produce a ≥ 95% (grade A) treatment success in H. pylori infected Thai subjects with nonulcer dyspepsia. Methods: Two prospective, but separate, pilot single‐center studies were carried out during September 2009–December 2010 at Thammasat University Hospital, Thailand. H. pylori infected subjects were randomized into the two pilot studies; either 5‐day or 10‐day concomitant therapy. Thai concomitant therapy consisted of rabeprazole (20 mg) twice daily, amoxicillin 1 g twice daily, metronidazole 400 mg three times a day, and clarithromycin MR 1 g once daily. H. pylori status was assessed by ¹³C‐urea breath test 4 weeks after completion of the treatment. Successful treatment was defined as achieving a grade A result (≥95%) and failure by <90% cured. Results: A total of 110 subjects were randomized (55 to the 5‐day treatment trial and 55 to the 10‐day regimen). Baseline subject demographic and clinical characteristics were similar in both studies. All subjects completed their assigned therapies. The 10‐day concomitant treatment trial was successful in 53 of the 55 subjects (96.4%; 95% CI 87.4–99.5%). The 5‐day concomitant pilot was judged to be a failure as only 49 of 55 subjects (89.1%; 95% CI = 77.7–95.8%) were cured. The frequency of adverse events was low and similar in the two studies. Conclusion: The 10‐day concomitant regimen provided excellent treatment success (eradication rate >95%) and was well tolerated. Ten‐day concomitant therapy is likely to become useful first‐line H. pylori eradication in Thailand.     

Helicobacter pylori infection and perforated peptic ulcer prevalence of the infection and role of antimicrobial treatment

Although the role of Helicobacter pylori infection on noncomplicated peptic ulcer disease has been definitively established, the precise relationship between the organism and complicated ulcer has hardly been studied. The mean prevalence of H. pylori infection in patients with perforated peptic ulcer is of only about 65-70%, which contrasts with the almost 90-100% figure reported in noncomplicated ulcer disease. However, H. pylori infection rates in various studies range markedly from 0% to 100%, suggesting that differences in variables as number and type of diagnostic methods used to diagnose H. pylori infection, or frequency of nonsteroidal anti-inflammatory drug intake, may be responsible for the low prevalence reported in some studies. Recurrent ulcer disease after peptic ulcer perforation mainly occurs in patients with H. pylori infection, which suggests that the microorganism plays an important role in this complication. All patients with perforated peptic ulcer should be treated by simple closure of the perforation and with therapy aimed at healing of the ulcer and eradicating the H. pylori infection, as disappearance of the organism prevents, or at least decreases, ulcer recurrence and ulcer perforation in patients with H. pylori-associated perforated ulcers after simple closure. Therefore, H. pylori eradicating treatment should be started during the immediate postoperative period. The patients with intractable recurrent symptoms of peptic ulcer despite adequate medical treatment, but without H. pylori infection (e.g. a patient using nonsteroidal anti-inflammatory drugs), is probably the only remaining indication for elective definitive surgical treatment of peptic ulcer disease.     

Eradicating Helicobacter pylori in Peptic Ulcer Disease Reduces Medical Costs in the Community

Background: Eradicating Helicobacter pylori markedly reduces ulcer recurrence in patients with peptic ulcer disease (PUD). Many decision analysis studies have concluded that eradicating H. pylori in PUD patients is more cost‐effective than maintaining antisecretory therapy. In 1995, we introduced an H. pylori eradication program into a large transportation company that experienced increased incidences of PUD among its employees along with increased medical costs, and we performed trend analysis of the actual medical costs of PUD in this cohort. Methods: In this cohort, there were approximately 8500 employees. H. pylori‐positive PUD patients were identified at the annual health check up. The patients received eradication therapy with lansoprazole, amoxicillin, and clarithromycin. After eradication, the patients were followed up by a yearly health check up. The annual number of patients who received eradication was recorded, and the annual direct medical costs of PUD therapy were analyzed. Results: A total of 440 H. pylori‐positive PUD patients received eradication therapy in a 7‐year period. Based on an intention‐to‐treat analysis, the eradication rate was 84.5% (372 of 440). The largest number of patients who received eradication therapy was found in 1995 (n = 115), and from 1995 to 2001 this number decreased yearly by 12.5 (95% confidence interval (CI): 5 to 20). Between 1989 and 1995, the annual medical costs arising of PUD therapy increased by ¥2.25 million (95% CI: 1.19 to 3.31) per year, being highest (¥22.75 million) in 1995. Between 1995 and 2001, the costs decreased by ¥3.88 million (95% CI: 3.16 to 4.59) per year. The cost in 2001 was 5.7% of the cost in 1995. The eradication program was terminated in 2001 because the prevalence of PUD diminished markedly, and the associated medical costs decreased as well. Conclusions: H. pylori eradication could reduce the number of PUD patients and associated medical costs in the workplace setting.     

Helicobacter pylori stool antigen test in patients with bleeding peptic ulcers

BACKGROUND: Helicobacter pylori has been linked to chronic gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Invasive tests are less sensitive than noninvasive tests in diagnosing H. pylori infection in patients with bleeding peptic ulcers. The H. pylori stool antigen test has been useful in diagnosing H. pylori in patients with peptic ulcers before and after eradication of H. pylori. The aim of this study was to evaluate the H. pylori stool antigen test in patients with bleeding peptic ulcers. METHODS: Patients with bleeding and nonbleeding peptic ulcers underwent a rapid urease test, histology, bacterial culture and H. pylori stool antigen test. Positive H. pylori infection was defined as a positive culture or both a positive histology and a positive rapid urease test. Helicobacter pylori stool antigen was assessed with a commercial kit (Diagnostec H. pylori antigen EIA Kit, Hong Kong). RESULTS: Between October 2000 and April 2002, 93 patients with bleeding peptic ulcers (men/women: 78/15, gastric ulcer/duodenal ulcer: 58/35) and 59 patients with nonbleeding peptic ulcers (men/women: 47/12, gastric ulcer/duodenal ulcer: 30/29) were enrolled in this study. Forty-seven (50.5%) patients with bleeding peptic ulcers and 30 (50.8%) patients with nonbleeding peptic ulcers, were found to be infected with H. pylori (p > .1). Helicobacter pylori stool antigen tests were positive in 54 (58.1%) and 30 (50.8%) patients with bleeding peptic ulcers and nonbleeding peptic ulcers, respectively (p > .1). The sensitivity (82% vs. 93%), specificity (68% vs. 93%), positive predictive value (74% vs. 93%), negative predictive value (77% vs. 93%) and diagnostic accuracy (75% vs. 93%) were all lower in patients with bleeding vs. nonbleeding peptic ulcers. The specificity, positive predictive value, and diagnostic accuracy of the H. pylori stool antigen test in patients with bleeding peptic ulcers were significantly lower than those in patients with nonbleeding peptic ulcers (p = .01, p = .02 and p = .003, respectively). CONCLUSION: The H. pylori stool antigen test is not reliable for diagnosing H. pylori infection in patients with bleeding peptic ulcers.     

幽门螺杆菌与 2005 年诺贝尔医学奖

今年的诺贝尔医学或生理学奖授予 Robin Warren 和 Barry Marshall 两位坚韧不拔且敢于挑战传统观念的科学家 . 奖励他们所做出的非凡的和出人意料的发现：慢性胃炎、胃溃疡以及十二指肠溃疡主要是由幽门螺杆菌感染所导致的 .     

Double-dose, new-generation proton pump inhibitors do not improve Helicobacter pylori eradication rate

BACKGROUND: Up to present, omeprazole plus two antibiotics are used for Helicobacter pylori eradication therapy . Few studies have compared double-dose new-generation, proton pump inhibitors (PPI) with omeprazole. Therefore, we conducted a randomized, prospective study to evaluate differences in H. pylori eradication rates by PPI type. MATERIAL AND METHODS: Between January 2006 and December 2006, 576 consecutive patients with proven H. pylori infection were enrolled prospectively. Four different PPIs [omeprazole 20 mg b.i.d. (old generation), or pantoprazole 40 mg b.i.d., rabeprazole 20 mg b.i.d., or esomeprazole 40 mg b.i.d. (new generation)] were added to clarithromycin (500 mg b.i.d.) and amoxicillin (1 g b.i.d.) for 1 week. RESULTS: By intention-to-treat analysis, no difference was found between the eradication rates of these four PPIs: 64.9% (omeprazole, n = 148), 69.3% (pantoprazole, n = 140), 69.3% (rabeprazole, n = 140), and 72.9% (esomoprazole, n = 148). When eradication rates were analyzed according to whether patients had an ulcer or not on a per-protocol basis, no difference was found between the eradication rates of the four PPIs. However, side-effects were more common in the esomeprazole-based triple therapy group than in the other groups (p < .05). CONCLUSIONS: No convincing evidence was obtained that double-dose new-generation PPIs have better H. pylori eradication rates and tolerability than omeprazole.     

Review: Helicobacter pylori and non‐malignant upper gastrointestinal diseases

This review covers recent publications investigating the relationship between Helicobacter pylori infection and gastroesophageal reflux disease, Barrett's esophagus, eosinophilic esophagitis, peptic ulcer disease (PUD), H pylori gastritis, and functional dyspepsia. In the area of gastroesophageal reflux disease, new data suggest that reflux may have a role in the transmission of H pylori infection. In addition to several observational studies, data on alterations in esophageal physiology in patients with H pylori infection are presented. Further evidence for the inverse relationship between H pylori infection and Barrett's esophagus is available in the form of a meta‐analysis from the North American Barrett's and Esophageal Carcinoma Consortium. The relationship between H pylori infection and eosinophilic esophagitis remains uncertain. Although new data do not indicate a significantly lower prevalence of H pylori among patients with eosinophilic esophagitis, a meta‐analysis showed a 37% reduced risk of eosinophilic esophagitis among H pylori‐infected patients. Novel data are presented on the genetic variability of bacterial virulence factors and their relationship with PUD. We also report data on plasma biomarkers, which may detect progression to gastric cancer in H pylori‐associated PUD. A new meta‐analysis was published, which assessed the risk of PUD in low‐dose aspirin users with H pylori infection. Finally, we report on the ongoing attempts to stratify patients with gastritis using endoscopic methods when compared to standard biopsy examination.     

Interaction of Helicobacter pylori Infection and Nonsteroidal Anti‐Inflammatory Drugs in Gastric and Duodenal Ulcers

Background: Gastric (GU) and duodenal ulcers (DU) are in most instances either induced by Helicobacter pylori infection or by nonsteroidal anti‐inflammatory drugs (NSAIDs). Whether eradication of H. pylori is beneficial in NSAID users for preventing NSAID induced GU and DU has been the focus of different studies. Materials and Methods: Mechanisms shared by both H. pylori and NSAIDs for the induction of GU and DU were reviewed and randomized controlled trials on H. pylori eradication for prevention and healing of GU and DU in patients requiring NSAID therapy were identified by a PubMed search. Results: Key factors in the induction of GU and DU for both H. pylori and NSAIDs are a decrease in pH, imbalance between apoptosis and proliferation, reduction in mucosal blood flow, and recruitment of polymorphonucleates in distinct compartments. For primary ulcer prevention, H. pylori eradication before starting an NSAID therapy reduces the risk of NSAID induced GU and virtually abolishes the risk of DU. H. pylori eradication alone is not sufficient for secondary prevention of NSAID induced GU and DU. H. pylori infection appears to further increase the protective effects of proton‐pump inhibitors (PPI) to reduce the risk of ulcer relapse. H. pylori eradication does not influence the healing of both GU and DU if NSAID intake is discontinued. Conclusions: Duodenal ulcer is more closely related to H. pylori infection than GU in NSAID users. H. pylori eradication is recommended for primary prevention of GU and DU in patients requiring NSAID therapy. PPI therapy is mandatory for secondary prevention of gastroduodenal ulcers, and appears to further reduce the risk of ulcer relapse in the presence of H. pylori.     

Helicobacter pylori and Gastroesophageal Reflux Disease: A Case–Control Study

Background:  Gastric colonization with Helicobacter pylori is a proposed protective factor against gastroesophageal reflux disease (GERD), but little population-based data exist and other data conflict.
Methods:  We conducted a case–control study within the membership of a large integrated health-care system that compared GERD-free subjects with two groups: subjects with a physician-assigned GERD diagnosis and randomly selected members with self-described weekly GERD symptoms. Subjects completed interviews, GERD questionnaires, and antibody testing for H. pylori and its cagA protein.
Results:  Serologic data were available for 301 physician-assigned GERD patients, 81 general membership subjects with GERD symptoms, and 175 general membership subjects without GERD symptoms. Physician-assigned GERD patients were less likely to have H. pylori antibodies than GERD-free member controls (odds ratio (OR) = 0.27, 95% confidence interval (CI) 0.15–0.47); there was also an inverse association between H. pylori and GERD symptom severity (OR = 0.18, 95% CI 0.08–0.41; severe or very severe symptoms) and GERD frequency (OR = 0.18, 95% CI 0.09–0.38; for symptoms at least weekly). The association was stronger among persons with erosive GERD and was similar between H. pylori -positive subjects with and without cagA. There was no association among persons who were cagA positive, but H. pylori negative. Similar findings were found in analyses of the general membership with self-described GERD symptoms.
Conclusions:  H. pylori antibody status was inversely associated with a GERD diagnosis and GERD symptoms compared with a general membership population.     

Review ‐ Helicobacter pylori and non‐malignant upper gastro‐intestinal diseases

This review takes into account recent publications focusing on the relationship between Helicobacter pylori infection and non‐malignant diseases of the upper gastro‐intestinal tract. The authors have summarized current knowledge on associations between the H pylori infection and non‐malignant upper GI conditions including gastroesophageal reflux disease (GERD), Barrett's esophagus, eosinophilic esophagitis (EOE), peptic ulcer disease (PUD), H pylori gastritis, celiac disease and functional dyspepsia. In the field of GERD, current data focusing on different locations of H pylori infection detect significant differences between antrum‐ and corpus predominant gastritis explainable by different changes in acid secretion in different gastric niches. High volume studies from Sweden and Brazil underline the safety of H pylori eradication concerning the risk of Barret's esophagus or adenocarcinoma. The relationship betweenH pylori infection and EOE remains uncertain, but current data supports the concept of expected positive and protective effects of H pylori exposure reducing the risk of EOE. Analyzing biomarkers might be helpful to identify subjects under risk for the development of precancerous lesions after H pylori infection, where microRNAs, IL‐9 and IL‐4, and also Tc17/9 and Th17/9 and microbiota profiles showed promising results to identify subgroups under risk.