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.     

Treatment of Helicobacter pylori infection

Helicobacter pylori infection has been shown to be the principal cause of peptic ulcer disease and has been associated with MALT lymphoma and gastric cancer. Eradication of H. pylori has been shown to change the natural history of peptic ulcer disease by preventing relapse and to reduce health care expenditures when compared with traditional therapy. Two-drug regimens have been superceded by three-drug regimens because they are more effective in eradication. Therapies with the highest efficacy are cost-effective because failed eradication is associated with high costs.     

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.     

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.     

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.     

The role of H pylori in gastrointestinal disease. A guide to identification and eradication

Helicobacter pylori, which is responsible for the most common infection worldwide, has been implicated in several gastrointestinal diseases, such as peptic ulcer disease, gastric adenocarcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma. In this article, Dr Knigge discusses the unique adaptation of H pylori to the acidic gastric environment and describes diagnostic tests to identify the organism, treatment recommendations, and tools to confirm eradication of infection.     

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.     

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.     

The perspectives of upper GI tract diseases

Recently, most of the upper GI tract diseases, peptic ulcer, chronic gastritis, gastric cancer as well as MALT lymphoma, have been explained by the infection of Helicobacter pylori (H. pylori). However, it is not evident whether or not gastric cancer is induced solely by the bacterial infection at this stage. On the other hand, it is reported that the eradication of H. pylori might evoke the reflux esophagitis as well as esophageal and fundic cancer. These important issues remain to be elucidated for the investigation of upper GI tract in the 21st century. The development of new endoscopic technology may be another promising field of upper GI tract.     

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.     

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.     

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.     

Treatment of Helicobacter pylori infections

The available literature on the relationship between severaldiseases and Helicobacter pylori (H. pylori) is reviewed. Duodenalulcer, gastric ulcer, complicated peptic ulcer, abdominal symptomsand gastroduodenal mucosal damage during the use of non-steroidalanti-inflammatory drugs (NSAIDs), non-ulcer dyspepsia (NUD)and gastric malignancy are discussed. The case for and againsteradication is critically discussed. Eradication of H. pylorishould be pursued in all patients with peptic ulcer disease,whether they are using NSAIDs or not. Eradication of H. pyloriin the treatment of NUD should be considered experimental. Treatmentaimed at the eradication of H. pylori should be considered inall patients with low-grade malignant mucosaassociated lymphoidtissue (MALT) lymphoma and in all patients with Menetrier'sdisease. Finally, this treatment should be considered in a subsetof H. pylori-infected patients who possibly are at an increasedrisk of gastric cancer: patients with a strong family historyof gastric carcinoma and patients in need of long-term treatmentwith a proton-pump inhibitor. In view of the importance of patientcompliance, the risk of side-effects and the possibility ofinducing metronidazole resistance when treatment with a metronidazole-containingregimen is used, treatment aimed at the eradication of H. pylorishould be carefully implemented and monitored.     

Causal relationship between Helicobacter pylori infection and upper gastroduodenal diseases

Helicobacter pylori infection causes chronic gastritis (nonatrophic gastritis), which progresses to atrophic gastritis and intestinal metaplasia over a period of decades. Atrophy may result from inflammation and apoptosis caused by H. pylori infection. H. pylori is an important risk factor for peptic ulcer disease. Duodenitis in the gastric metaplasia of the duodenum, hypergastrinemia, and impaired proximal duodenal mucosal bicarbonate secretion are considered causal factors for duodenal ulcer disease. Low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue (MALT) develops in response to H. pylori infection. Studies of Mongolian gerbil model demonstrated that H. pylori had an initiator or promoter effect on gastric carcinogenesis.     

Helicobacter pylori: ENOUGH TO GIVE ANYONE AN ULCER!

SUMMARY Since the early 1980s, research into gastritis and peptic ulcer disease has been dominated by Helicobacter pylori. This is a small, Gram-negative spiral bacterium which inhabits the mucus layer that coats the gastric mucosa. Colonisation of the human stomach by this bacterium is worldwide and, in certain continents, virtually ubiquitous. While histological gastritis is always the result, H. pylori-positive individuals are characteristically asymptomatic. Transmission is thought to be via the faecal-oral route and infection, usually acquired in childhood, will persist unless treatment supervenes. H. pylori is the main causative agent of peptic ulceration, but its role in non-ulcer dyspepsia is less clearcut. Recently epidemiological, histological and experimental data have been described linking H. pylori to gastric neoplasia — in particular adenocarcinoma and MALT lymphoma. A variety of treatment modalities exists for the eradication of this bacterium, and for adults the recommended drug therapy is a combination course of tetracycline, bismuth and metronidazole. Currently the new combination of omeprazole and amoxycillin is suggested as second-line treatment after failed triple therapy.     

Gastric mucosal immunity induced by H. pylori infection

H. pylori infection induces various humoral and cellular immunities in gastric mucosa. Some reports indicate predominant CD4+ cells infiltrate in H. pylori infected gastric mucosa, and these cells express the T helper 1 phenotype. Local humoral immunity is also induced. Gastric plasma cells produce anti-H. pylori antibodies, however, their protective immunity is not enough to eradicate bacteria in human. We found heat shock protein 60 kDa (hsp60) may be closely associated with pathogenesis in MALT lymphoma. IgG1 antibodies to hsp60 were significantly correlated with the antibodies to H. pylori whole cell in patients with MALT lymphoma. CD40-CD40L dependent B cell proliferation was induced by cytokine and/or hsp60 stimulations in those patients. Cytotoxicity of gastric epithelial cells which is associated with host immunity induced by H. pylori infection is still unclear. We found that lymphocytes from patients with peptic ulcer showed cytotoxicity to gastric cell line HGC-27 in vitro. Cytotoxicity was enhanced by cytokine stimulus to T-lymphocytes and by heat stress and/or patients' antibodies treatment of HGC-27 cells. The pathogenicity of H. pylori may involve not only bacterial virulence factor but also host immunity. Studies of mucosal local immunity will help explain the mechanisms of H. pylori induced gastrodoudenal diseases.     

Peptic ulcer disease

Peptic ulcer disease is a common gastrointestinal disease whose management and treatment has changed dramatically over the last 25 years. Treatment of peptic ulcer disease has evolved from dietary modifications and antacids to gastric acid suppression with H2-receptor antagonists and proton pump inhibitors to eradication of Helicobactor pylori infection. Treatment of patients infected with H pylori using antibiotics has changed the natural history of peptic ulcer disease. As a result of H pylori treatment and other unknown factors ulcer disease is declining and complications from ulcer disease have diminished significantly.     

Eradication of Helicobacter pylori: recent advances in treatment

Helicobacter pylori plays a key role in dyspepsia, peptic ulcer disease, and gastric neoplasia and eradication of the infection has become an important treatment goal in clinical practice. Seven-day proton-pump inhibitor-amoxicillin-clarithromycin triple therapy is the current first-line therapy for H. pylori but eradication rates are compromised by poor compliance and antibiotic resistance. Ten-day sequential treatment may emerge as an alternative first-line therapy. Bismuth-based quadruple therapy is the second-line regimen of choice. Antimicrobial sensitivity testing is not recommended in the routine management of H. pylori infection. Novel triple-therapy regimens containing rifabutin, levofloxacin, or furazolidone may be useful alternatives as second- or third-line therapy.     

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。