Role of Helicobacter pylori eradication in the prevention of peptic ulcer in NSAID users

Helicobacter pylori (H. pylori) and non-steroidal anti-inflammatory drug (NSAID) are independent risk factors for peptic ulcers and ulcer complications and they have additive or synergistic effects. A meta-analysis showed that the OR for the incidence of peptic ulcer was 61.1 in patients infected with H. pylori and also taking NSAID when compared to patients uninfected with H. pylori and not taking NSAID. H. pylori eradication may prevent NSAID-induced ulcers in NSAID naive patients. In patients receiving long-term NSAID, proton pump inhibitor(PPI) is more effective in the prevention of ulcer recurrence and bleeding. However, H. pylori eradication should be considered in patients receiving long -term PPI maintenance treatment to prevent the development of corpus gastritis and gastric atrophy.     

Ulcers and gastritis

This article reviews recently published literature regarding ulcers and gastritis. Although endoscopy is the most useful procedure for diagnosis in the upper gastrointestinal tract, complications do occur, and procedure-related costs are significant. The appropriate indication for endoscopy has recently been debated. Helicobacter pylori is known to be an important pathogen involved in gastric and duodenal inflammation. Peptic ulcer disease and severe gastric mucosal injury are caused by virulent strains, and many reports have focused on CagA. Follow-up studies on surveillance endoscopy in patients with peptic ulcer or gastritis report that patients with atrophic gastritis and intestinal metaplasia are at significantly higher risk for gastric cancer. H. pylori eradication sometimes causes gastroduodenal erosion and reflux esophagitis, and the mechanisms involved have been revealed. Proton-pump inhibitors are useful in the treatment of ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs), reflux esophagitis, and for preventing rebleeding after endoscopic hemostasis, but the effect of long-term acid suppression on the gastric mucosa is still a matter of debate. H. pylori infection and NSAID intake are both risk factors for peptic ulcer disease, and are important aspects in this field.     

Ulcer and gastritis

The literature on peptic ulcer and gastritis in 2000 again focused on the topics of Helicobacter pylori, nonsteroidal anti-inflammatory drugs (NSAIDs), and gastric cancer. New diagnostic tests for H. pylori infection have been evaluated, and rescue therapies for failed H. pylori eradication have been tested. The causal relationship between H. pylori infection and nonulcer dyspepsia, gastric cancer, gastroesophageal reflux disease, and NSAID-related ulcers remained heated topics of debate. In 2000, landmark clinical trials and meta-analyses were published addressing these issues. The role of endoscopy in managing nonulcer dyspepsia was better defined. The role of H. pylori eradication in NSAID/aspirin users was reexamined in high-risk patients. Clinical benefit was finally confirmed for specific inhibitors of cyclooxygenase-2 (COX-2). The millennium year turned out to be a very important one in the advancement of knowledge in this field.     

Guidelines in the management of Helicobacter pylori infection in Japan--in comparison with the guidelines published in other countries

Helicobacter pylori(H. pylori) is a causative agent for chronic gastritis and is an important risk factor for peptic ulcers, gastric carcinomas, and gastric MALT lymphomas. In 2000, the Japanese Society for Helicobacter Research published a guideline on the diagnosis and treatment of H. pylori infection for physicians in routine medical practice. In this guideline, H. pylori eradication therapy is recommended in gastric or duodenal ulcer patients. H. pylori eradication is also recommended in gastric MALT lymphoma patients but the guideline says it should be done at specialist institutions. Considering the high prevalence of gastric carcinomas in Japan. H. pylori eradication for the prevention of gastric carcinomas should be discussed urgently.     

Guidelines for the management of Helicobacter pylori--Maastricht III-2005 and Japanese guidelines

The guidelines on the management of Helicobacter pylori were updated at the European Helicobacter study group third Maastricht consensus conference in March 2005. Especially, this conference emphasis on the management of non ulcer dyspepsia, GERD, and the patients who use non steroidal anti-inflammatory drug. Eradication of H. pylori is recommended in patients with peptic ulcer, low grade MALT lymphoma, atrophic gastritis, unexplained iron deficiency anemia, chronic idiopathic thrombocytopenic purpura and first degree relatives of patients with gastric cancer. H. pylori eradication is less effective than proton pomp inhibitor(PPI) treatment in preventing ulcer recurrence in long term NSAIDs users. This meeting also emphasized on the relationship between H. pylori and gastric cancer. The guideline concluded that H. pylori eradication has the potential to reduce the risk of gastric cancer development. Japanese guideline in 2003 does not mention the effect of eradication for prevention of gastric cancer. The H. pylori eradication and new strategy should be desirable for global strategy of gastric cancer prevention.     

Indication of H. pylori eradication therapy

In the guideline, for H. pylori the Japanese Society of Helicobacter published diagnosis and treatment in July 2000. Only peptic ulcers and low grade MALT lymphomas are recommended as an indication of H. pylori eradication and other diseases such as atrophic gastritis, post EMR state for early gastric cancer and post-operated stomach due to gastric cancer, hyperplastic polyps and non-ulcer dyspepsia, were not included. In addition, Japanese social security foundation approves only peptic ulcers for indication of H. pylori eradication treatment. However, eradication therapy for atrophic gastritis should be considered in aspect of decreasing gastric cancer risk. Since accumulated epidemiological, experimental and clinical data strongly support its positive correlation with cancer risk, patients in high risk group for gastric cancer should be included for a target eradication therapy. Indication of the treatment should be expanded to histological gastritis caused by H. pylori in our country, where prevalence of gastric cancer is very high.     

Current state and measures of NSAIDs induced ulcer

In recent years, the incidence of Helicobacter pylori (H. pylori) infection has been decreasing and the incidence of peptic ulcer and bleeding ulcer induced by NSAIDs, especially low-dose aspirin (LDA), have been increasing. PPI and PG are useful for treatment and prevention of ulcers in patients receiving continuous administration of NSAIDs and/or LDA. H. pylori eradication is effective if performed before the start of NSAIDs administration, but a beneficial effect of H. pylori eradication performed during NSAIDs treatment cannot be expected. The incidence of ulcers is lower when administering COX-2-selective inhibitor than when administering non-selective NSAIDs, but attention must be given to cardiovascular events as side effects when administering COX-2-selective inhibitor.     

Effects of Helicobacter pylori eradication therapy on the healing process of peptic ulcers

The advent of H2-receptor antagonists (H2RA) and proton pump inhibitors (PPI) has particularly revolutionized the treatment of peptic ulcer disease. Most cases can now be successfully controlled by medical treatment with H2RA and PPI, but a high rate of ulcer recurrence remains an important problem. The quality of ulcer healing (QOUH) has therefore received increasing attention, and various investigators have attempted to define the conditions required for nonrecurrence. Ulcer scars with a good QOUH are considered to have a very low risk of recurrence. Recent studies have confirmed that recurrence of peptic ulcer can be suppressed markedly by eradication of Helicobacter pylori (H. p). Moreover, various types of endoscopic examinations (conventional observation, dye-contrast endoscopy, magnifying endoscopy, endoscopic ultrasonography, pharmacoendoscopy) have confirmed that the QOUH after eradication of H. p is better than that after conventional anti-ulcer therapy. H. p eradication therapy may become treatment of first choice for peptic ulcers.     

H. pylori infection and GI disease: what critical care physicians need to know. Who should be tested for H. pylori? When is treatment needed?

Helicobacter (Campylobacter) pylori infection has emerged as a major cause of gastritis, peptic ulcers, and gastric malignancies. Not all patients with H. pylori infection require treatment; however, for those with ulcer disease (particularly those with bleeding), antibiotic therapy can be curative. To confirm infection (or its eradication), use the rapid urease assay, serologic examination or, when available, the urea breath test. Treatment options include triple therapy (with bismuth subsalicylate, metronidazole, and either tetracycline or amoxicillin) and dual therapy (with omeprazole and either amoxicillin or clarithromycin). For patients with an active ulcer, follow antibiotic therapy with ranitidine or omeprazole.     

Eradication of Helicobacter pylori in Japan]

Twenty five years has passed since the re-discovery of Helicobacter pylori. Many people have studied on this organism since that time. Some mechanisms about gastric mucosal inflammation have been clarified, and pathogenesis of peptic ulcer formation and gastric cancer have been solved. H. pylori infection is related to chronic gastritis, peptic ulcer, gastric carcinoma, and MALToma. In 1998, it was reported that gastric cancer occurred in H. pylori infected mongolian gerbils. In Japan, the prevalence of peptic ulcer and gastric cancer is very high. Therefore, the treatment for H. pylori infection is necessary to prevent occurrence of these diseases. To treat H. pylori infection, various regimen have been tried. Triple therapy with PPI and two antibiotics is recommended for cure of H. pylori infection in European and US guidelines. Some guidelines for management of H. pylori infection and regimen were shown in this part.     

Indication of H. pylori eradication therapy--who should be treated?

With increased evidence of H. pylori infection being deeply related with various gastric diseases, its curative therapy will be approved by social security foundation soon also in Japan. Japanese Society of Helicobacter reported a guideline for H. pylori diagnosis and treatment in July 2000. In the guideline, only peptic ulcers and low grade MALT lymphomas are recommended as an indication of H. pylori eradication and other diseases such as atrophic gastritis, post EMR state for early gastric cancer and post-operated stomach due to gastric cancer, hyperplastic polyps and non-ulcer dyspepsia, were not included. It is speculated that while benefit of eradication therapy for peptic ulcers and low grade MALT lymphomas has been supported by much clinical evidence, that for other diseases was judged not to be enough. Especially as to atrophic gastritis, eradication therapy might be considered in aspect of decreasing gastric cancer risk in Japan. Since accumulated epidemiological and experimental data strongly support its positive correlation with cancer risk, patients in high risk group for gastric cancer could be included for a target eradication therapy. In present, indication of the therapy should be clinically and socially decided according to individual patient.     

长春地区慢性胃病患者幽门螺杆菌感染状况调查

目的通过对本地区慢性胃病患者幽门螺杆菌（H.pylori）感染状况调查,了解本地区流行病学特点,为进一步阐明其与慢性胃病发生发展的关系提供理论依据。方法采用ELISA方法测定血清H.pyloriIgG抗体及CagA抗体;采取胃粘膜活检组织进行快速尿素酶试验,调查H.pylori感染情况,分析其与各种疾病的关系。结果1180例慢性胃病患者H.pylori感染率为67.11%,复合性溃疡、十二指肠溃疡、胃溃疡及慢性萎缩性胃炎感染率分别为90.9%、84.57%、83.96%和80.24%。与慢性浅表性胃炎相比差异有显著性。消化性溃疡、慢性萎缩性胃炎、胃癌和胃息肉患者血清Hp-CagA抗体的阳性率明显高于慢性浅表性胃炎（P〈0.05）。结论本地区慢性胃病患者H.pylori感染率高与多数地区的普通人群,H.pylori感染者尤其是CagA阳性者,更易发生慢性萎缩性胃炎、消化性溃疡及胃癌。     

Helicobacter pylori as a new paradigm in the pathogenesis of upper GI diseases

Discovery of H. pylori from human gastric mucosa have induced an evolution in the concepts of upper GI diseases, especially in those of gastritis, peptic ulcer and gastric cancer. A new classification of gastritis, Sydney system and updated Sydney system, are proposed and commonly used in worldwide. Eradication treatment against H. pylori infection can completely improve the histologic gastritis, which is defined by the infiltration of inflammatory cells. In gastric and duodenal ulceration, the eradication of H. pylori accelerates the ulcer healing without acid suppression, and prevents the ulcer recurrence without any maintenance therapy. These accumulating data suggest that H. pylori could have an etiologic relation to ulcer diseases, because these are a kind of intervention study on etiology. Thus, in ulcer diseases, H. pylori is proven to play an etiologic role. On the basis of these studies, a new treatment strategy is proposed in upper GI diseases. This is a new paradigm on upper GI diseases.     

New Therapeutic Approaches to Peptic Ulcer Disease: The Role of Helicobacter Pylori

One of the most common bacterial infections of human involves Helicobacter pylori, a spiral, gram-negative bacterium that is now thought to be a dominant factor in the development of peptic ulcer disease and may be significant in causing certain forms of gastric cancer. Almost 100% of patients with duodenal ulcer and 70 to 90% affected with gastric ulcer are infected with H. pylori. In order to achieve cure of H. pylori--induced ulcer disease, it is necesary to eradicate the bacterial infection. Mere suppression or clearance infection without eradication is associated with a >80% recurrence of the ulcer. The epidemiology, microbiology, and pathogenesis of H. pylori infections are reviewed. Diagnostic methods and optimal treatment strategies for H. pylori infections are examined. The most current diagnostic and treatment algorithms for peptic ulcer disease are discussed critically, and future directions for drug development aimed at eradication of H. pylori infection are considered.     

Helicobacter pylori: why it still matters in 2005

Despite falling prevalence rates in the developed world, H pylori is still present in the United States and is particularly prevalent among racial minorities and recent immigrants. H pylori infection is clearly associated with an increased risk of peptic ulcer disease, gastric cancer, and MALT lymphoma, and it is associated with some cases of uninvestigated dyspepsia. Identification and eradication of H pylori improves outcomes in patients with peptic ulcer disease and causes tumor regression in patients with MALT lymphoma. It is uncertain whether H pylori eradication will improve outcomes in patients with gastric cancer. Decision analytic models suggest that a test-and-treat strategy for H pylori is rational and cost-effective for patients with uninvestigated dyspepsia.     

Future for basic and clinical studies on peptic ulcer disease

Since the discovery of H. pylori, various causes of peptic ulcer disease is reevaluated, and only four factors are now considered most important; H. pylori infection, gastric acid, NSAID administration, and mental and physical stress. Among them, gastric acid is an aggravating factor, and gastric acid alone can hardly develop peptic ulcers. The relationship between H. pylori infection and stress has been studied at Hanshin-Awaji great earthquake occurred in 1995. Immediately after the earthquake, the number of patients with peptic ulcer disease has been greatly increased, and those patients were considered to be typical cases of stress ulcers. Interestingly, however, it was found that 83.2% of the patients were infected with H. pylori. The data suggested that stress ulcer developed in those infected with H. pylori. In contrast, the relationship between H. pylori infection and NSAID in the development of ulcer disease is more complex. It is still unclear whether H. pylori infection is an additive effect for development of peptic ulcer disease by NSAID administration or not.     

Helicobacter pylori infection and eradication

H. pylori infection is associated with various gastroduodenal diseases such as gastritis, peptic ulcer, gastric cancer, gastric MALT lymphoma. H. pylori infection is suggested that it plays a role as protective factor not promoting factor for reflux esophagitis and GERD. Epidemiological studies showed lower prevalence of H. pylori infection in reflux esophagitis and Barrett's esophagus comparing the control. Increased occurrence of reflux esophagitis after curing of H. pylori infection was reported. However, the relationship between H. pylori infection and reflux esophagitis has not been actually made clear. Also the mechanism of reflux esophagitis occurrence after H. pylori eradication is not obscure.     

Influence of H. pylori infection on upper gastrointestinal damage

H. pylori infection and low-dose aspirin (LDA) are not only independent causal factors of peptic ulcer and gastrointestinal bleeding, they also have synergistic and additive effects. H. pylori infection rate has drastically decreased over the past decade to 34.3% amongst people in their 40's, 28.0% amongst those in their 30's, and 15.7% amongst those in their 20's. Therefore, LDA are expected to become more important factor of peptic ulcer in the near future. The incidence of peptic ulcer induced by LDA was 15.8% (16/101) in authors' hospital. Deep ulcers(more than proper muscularis layer) were only 4 cases, shallow ulcers(submucosal layer) were 12 cases. All deep ulcers were gastric ulcers (3 H. pylori positive, 1 negative), on the other hand shallow ulcers were 8 gastric ulcers (3 H. pylori positive, 5 negative), and 4 duodenal ulcers (1 H. pylori positive, 3 negative). Majority of peptic ulcers induced by LDA were shallow, and independent on H. pylori infection.     

Pathogenesis of gastric and duodenal ulcer in the elderly

In the elderly, H. pylori infection and nonsteroidal anti-inflammatory drug(NSAID) use are most important risk factors for peptic ulcer disease. It is now recognized that, in patients with H. pylori infection, nonatrophic antral-predominant gastritis results in increased acid secretion, which is seen in duodenal ulcer patients, whereas corpus-predominant gastritis and pangastritis result in decreased acid secretion, that are seen in patients with proximal gastric ulcer and gastric cancer. These physiological changes are considered to be related to disease outcome. On the other hand, NSAIDs induced gastrointestinal toxicity is primarily due to the inhibition of mucosal prostaglandin synthesis in the gastric mucosa, which subsequently impairs the gastric cytoprotective factors. These two factors may independently, or even synergistically, cause the development of peptic ulcer disease in the elderly.     

Helicobacter pylori associated antral gastritis in peptic ulcer disease patients and normal healthy population of kashmir, India

Aim: To study the association of Helicobacter pylori infection with chronic antral gastritis in peptic ulcer disease patients and healthy population of Kashmir.Methods: 50 peptic ulcer patients (duodenal ulcer = 46, gastric ulcer = 2 and combined duodenal and gastric ulcer = 2) and 30 asymptomatic healthy volunteers were included in this study. Peptic ulcer was diagnosed on endoscopic examination. 4-6 punch biopsies were taken from gastric antrum in all the individuals and in case of gastric ulcer an additional biopsy was taken from the edge of the ulcer to exclude its malignant nature. Helicobacter pylori (H. pylori) organism was diagnosed using three different test methods, viz. Histology (using Giemsa Stain), Microbiology (Gram Stain) and Biochemistry (using one minute Endoscopy Room Test). Histological diagnosis of H. pylori was taken as the "gold standard" for the presence of H. pylori organism. Histological diagnosis of gastritis was made using Hematoxylin and Eosin Stain and the gastritis was classified as active chronic gastritis and superficial chronic gastritis.Results: Out of 30 peptic ulcer disease patients with associated antral gastritis, 27 (90%) were positive for H. pylori on histological examination (13 superficial chronic gastritis and 14 active chronic gastritis) whereas out of 8 healthy volunteers with histological evidence of chronic antral gastritis, H. pylori was observed in 7 individuals (87.50%) (4 active chronic gastritis and 3 superficial chronic gastritis).Conclusion: A highly significant association between H. pylori infection with chronic antral gastritis both in peptic ulcer disease patients and healthy volunteers of Kashmir was found in this study. Association between H. pylori infection and chronic gastritis was 90% in peptic ulcer group and 87.50% in healthy population (P<0.005).