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.     

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.     

Ulcers and gastritis

This article reviews recently published reports on ulcers and gastritis. Helicobacter pylori is known to be an important pathogen involved in gastroduodenal inflammation and peptic ulcers. Conventional endoscopy is of limited usefulness in the evaluation of gastritis, but magnifying endoscopy is evidently helpful in the diagnosis of chronic atrophic gastritis, intestinal metaplasia, and H. pylori infection. A significant reduction in the incidence of refractory ulcers and the prevalence of H. pylori infection in patients with peptic ulcer disease followed the introduction of H. pylori eradication treatment. Chronic H. pylori infection is associated with gastric cancer, and the effect of H. pylori eradication on the prevention of gastric cancer is an important issue that is still a matter of controversy. Endoscopic hemostasis and intravenous proton-pump inhibitor (PPI) infusion represent a widely accepted approach to the treatment of peptic ulcer bleeding. In clinical practice, it is important to prevent recurrent bleeding and to treat patients who do not respond to endoscopic therapy or PPI treatment. Laparoscopic repair for peptic ulcer perforations, with postoperative eradication treatment, has gradually met with acceptance in patients with H. pylori infection. H. pylori infection and its treatment continue to be interesting problems in this field.     

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.     

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.     

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.     

Evidence-based recommendations for older adults with Helicobacter pylori or those using nonsteroidal anti-inflammatory drugs.

Currently, about half the world's population is infected with Helicobacter pylori. This organism is known to cause peptic ulcers and places patients at higher risk for gastric cancer. Older adults are more susceptible to the negative effects of Helicobacter pylori infection. In addition, this population consumes large amounts of nonsteroidal anti-inflammatory drugs and typically demonstrates a high incidence of atrophic gastritis, both of which place them at even higher risk for gastrointestinal disease. Consequently, older adults should be carefully assessed for gastrointestinal irritation, peptic ulcer, and gastric cancer. Age-specific therapy can result in improved outcomes related to a lower incidence of nonadherence with medications, decreasing hospital admissions, lowering costs of care, and increasing quality of life.     

Barrett's esophagus and Helicobacter pylori

Lifestyles of Japanese, including eating habits, have been similar to those in Western countries, which might be related to an increase in gastroesophageal reflux disease (GERD) in Japan. Barrett's esophagus is generally accepted as a complication of chronic and severe GERD. Helicobacter pylori (H. pylori) is a pathogen that is associated with atrophic gastritis, peptic ulcer disease, gastric adenocarcinoma, mucosa-associated lymphoid tissue lymphoma, and so on. The relationship between H. pylori and GERD+ Barrett's esophagus is controversial. H. pylori eradication therapy may increase the risk for the development of GERD, which may lead to increase a risk factor of Barrett's esophagus and esophageal adenocarcinoma. This review gives the outline regarding GERD and the relation between Barrett's esophagus and H. pylori infection.     

Helicobacter pylori eradication and associated changes in the gastric mucosa

Persistent Helicobacter pylori infection contributes towards the development of chronic gastritis. To clarify the changes in chronic gastritis as a precursor of gastric cancer secondary to H. pylori eradication is an important issue, as it has significant implications for reducing the risk of gastric cancer. Studies published to date, however, are far from consistent with regard to the morphologic changes reported following H. pylori eradication. Of these, some papers reported improvement in gastric atrophy or intestinal metaplasia, versus others reporting no improvement, with the majority of papers published after 2000 reporting improvement in these end points. The inconsistent results concerning the impact of H. pylori eradication on gastric atrophy could be due to the inconsistency of the diagnostic criteria employed for evaluation of the morphology, confounded by the difficulties involved in evaluating atrophic changes in the gastric mucosa. While adherence to the Updated Sydney System available for evaluation of gastritis is primarily required worldwide to ensure consistency in evaluating gastritis, long-term research into the morphologic changes associated with H. pylori eradication is also required to explore strategies for the prevention of gastric cancer with H. pylori eradication.     

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。     

The present status and problems of Helicobacter pylori eradication therapy with a special reference to gastric cancer

Since the eradication therapy of Helicobacter pylori(H. pylori) for peptic ulcer was covered by Japanese health insurance at 2000 November, this therapy has been generalized in Japan. However, some problems have cropped up at the time, for example, emergence of clarithromycin resistant bacterium etc. On the other hand, investigation of relation between H. pylori and gastric cancer is making progress. Uemura, et al. demonstrated H. pylori had an important role for gastric carcinogenesis by the elegant prospective study in 2001. Under the present circumstances, the Japanese society of Helicobacter Research has to reconsider the guideline for eradication therapy. In this paper, we would like to state the present status and problems of eradication therapy of the current guideline for eradication therapy, especially focusing on gastric cancer.     

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.     

Helicobacter pylori-related cytokines influence gastric acid secretion and gastric mucosal inflammation in gastroduodenal ulcers

Helicobacter pylori(H. pylori) is an important pathogenic factor for gastroduodenal ulcers and gastric cancer. The level of gastric acid output may influence the outcome of those diseases. With low acid output, H. pylori can spread to the corpus of the stomach, resulting in progression to atrophic gastritis. It may cause an increased risk of gastric cancer and ulcer. In contrast, with high output, H. pylori is confined in the gastric antrum, which develops antrum-predominant gastritis. This may contribute to an increased risk of duodenal ulcer. It is well known that inflammatory cytokines including interleukin (IL)-1 beta, IL-8 and tumor necrosis factor alpha modulate gastric acid secretion. Therefore, the host immune response by the cytokines may cause these disparate pathways in gastric acid secretion.     

Helicobacter pylori infection in gastric remnant cancer after gastrectomy

Patients who have undergone distal gastrectomy for peptic ulcer are at higher risk of developing gastric remnant cancer, and chronic bile reflux is believed to increase the risk of cancer in remnant stomach. In remnant stomach, carcinogenesis may be prevented by selecting the anastomosis method with a few reflux of intestinal juice including a bile acid. How Helicobacter pylori(H. pylori) infection participate in stomal gastritis and gastric remnant cancer, same as early gastric cancer in the intact stomach, is attended. H. pylori positive rate of remnant stomach is different by examination method and a report, but its rate is decreased every year after gastrectomy and in particular low in Billroth-II(B-II) anastomosis. B-II anastomosis is followed by a significantly lower rate than B-1. This may reflect the role of bile reflux because bile reflux interferes with colonization by H. pylori. Gastric cancer excision usual increase complicates gastric remnant stomach and H. pylori infection, but while H. pylori infection lasts after gastrectomy for gastric cancer, cell proliferation increase in remnant stomach. In remnant stomach after gastrectomy for gastric cancer, while H. pylori infection continues, H. pylori infection may cause remnant gastritis and a second cancer of remnant stomach. H. pylori infection and bile reflux seem to have a synergistic effect on cell proliferation in remnant stomach and may explain the increased risk of gastric remnant cancer. The cancer-causing dominant role might changed from H. pylori infection predominance to bile reflux every year after gastrectomy. Furthermore, a prophylactic effect to carcinogenesis by H. pylori eradication therapy is expected. Eradication of H. pylori after gastrectomy for gastric cancer has been recommended.     

Improvement in gastric histology following Helicobacter pylori eradication therapy in Japanese peptic ulcer patients

We aimed to determine if successful or failed eradication of Helicobacter pylori with triple therapy causes any difference in gastric mucosal histology. Japanese H. pylori-positive patients with a healed peptic ulcer received high (n = 112) or low (n = 113) doses of triple therapy (omeprazole, amoxicillin and clarithromycin) for 1 week. Biopsies from the greater curvature of the central antrum and upper corpus were taken 6 weeks and 30 weeks after treatment completion, and gastric mucosal histology compared between successful (n = 171) and failed (n = 34) eradication groups. Morphological variables of gastritis were graded according to the updated Sydney System. Successful eradication therapy was defined as improvement in inflammation, neutrophil activity and atrophy; failed eradication therapy as improvement in inflammation and neutrophil activity only. Gastric mucosal atrophy gradually improved (in addition to improvements in inflammation and neutrophil activity) with successful eradication of H. pylori infection.     

两种常用根除幽门螺杆菌三联方案的疗效观察

目的：观察两种常用一线根除幽门螺杆菌（H.pylori）三联方案在本地区（成都市）的疗效。方法：纳入70例诊断为消化性溃疡、慢性糜烂性胃炎、慢性萎缩性胃炎伴H.pylori感染的患者。随机分为A、B两组。A组采用埃索美拉唑（E）20 mg bid＋克拉霉素（C）500 mg bid＋甲硝唑（M）400 mg bid,B组采用E 20 mg bid＋C 500 mg bid＋阿莫西林（A）1.0g bid治疗,疗程7天。H.pylori根除失败者以1周四联方案：E 20 mg bid＋胶体次枸櫞酸铋（B）220 mg bid＋呋喃唑酮100 mg bid＋A1.0g bid治疗,观察疗效。结果：64例完成实验。三联方案H.pylori根除率：A组62.5%,B组84.4%,有显著差异（P〈0.05）。二线四联方案根除率94.1%。结论：ECA方案H.pylori根除率明显高于ECM方案,可能更适合于本地区根除H.pylori的一线治疗,EBFA方案作为二线治疗具有较高疗效。     

Anti-ulcer therapy after eradication of Helicobacter pylori

Helicobacter pylori (H. pylori) infection is the cause of the frequent relapse of peptic ulcer disease. Successful eradication therapy of H. pylori is associated with a decline in the recurrence of peptic ulcer. In this paper, we discussed the significance of anti-ulcer therapy after H. pylori eradication therapy. In patients with duodenal ulcer, maintenance therapy for preventing ulcer recurrence is not necessary because the rate of ulcer recurrence after eradication therapy is very low. However, in patients with gastric ulcer, the rate of ulcer relapse and reflux esophagitis ranges between 5-10% in the Japanese population even after successful eradication therapy; therefore, maintenance therapy for 1 year may be permissible in patients with gastric ulcer even after successful eradication therapy.     

The role of Helicobacter pylori in gastroduodenal disease.

Peptic ulcers are the result of a wide variety of factors, with H. pylori probably being one of the more significant. H. pylori has been most strongly associated with gastritis and duodenal ulcer disease. The relationship of H. pylori to gastric ulcers is less substantial. The eradication of H. pylori can be achieved in the majority of patients with triple antibiotic therapy. However, resistance to metronidazole occurs readily. Eradication of H. pylori can change the course of duodenal ulcer disease by decreasing recurrence rate from 80% to zero. Nonetheless, treatment for H. pylori should only be done in randomized trials at the current time because of the lack of completely effective therapy and the high risks of side effects. The mechanism by which H. pylori influences duodenal ulcer recurrence is unclear. Pathogenic mechanisms of the organism also need to be further elucidated.     

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.     

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.