Update on Helicobacter pylori treatment

One half of the world's population has Helicobacter pylori infection, with an estimated prevalence of 30 percent in North America. Although it is unclear whether eradication of H. pylori improves symptoms in patients with nonulcer dyspepsia, there is strong evidence that eradication of this bacteria improves healing and reduces the risk of recurrence or rebleeding in patients with duodenal or gastric ulcer. A "test-and-treat" strategy is recommended for most patients with undifferentiated dyspepsia. With this approach, patients undergo a noninvasive test for H. pylori infection and, if positive, are treated with eradication therapy. This strategy reduces the need for antisecretory medications as well as the number of endoscopies. The urea breath test or stool antigen test is recommended. Until recently, the recommended duration of therapy for H. pylori eradication was 10 to 14 days. Shorter courses of treatment (i.e., one to five days) have demonstrated eradication rates of 89 to 95 percent with the potential for greater patient compliance. A one-day treatment course consists of bismuth subsalicylate, amoxicillin, and metronidazole, all given four times with a one-time dose of lansoprazole. In children with documented H. pylori infection, however, all regimens should continue to be prescribed for seven to 14 days until short-course treatment is studied and its effectiveness has been established in this population.     

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.     

Helicobacter pylori: controversies and an approach to management

Helicobacter pylori (formerly, Campylobacter pylori) is a gram-negative, spiral-shaped bacterium with a strong affinity for gastric-type epithelium. Convincing evidence indicates that H. pylori plays an etiologic role in the development of chronic, nonspecific gastritis, and it may play an important role in the pathogenesis of duodenal ulcer disease. An etiologic role for this organism in chronic gastric ulceration, nonulcer dyspepsia, and gastric carcinoma is not established. Whereas the diagnosis of H. pylori infection is relatively straightforward, the questions of when and how to treat the infection do not have established answers. A high rate of recrudescence follows most currently used therapeutic interventions. Until the pathogenicity of H. pylori in clinical disease is further supported and additional treatment trials have been completed, a conservative management approach is recommended.     

Evaluation and management of nonulcer dyspepsia

When no organic cause for dyspepsia is found, the condition generally is considered to be functional, or idiopathic. Nonulcer dyspepsia can cause a variety of symptoms, including abdominal pain, bloating, nausea, and vomiting. Many patients with nonulcer dyspepsia have multiple somatic complaints, as well as symptoms of anxiety and depression. Extensive diagnostic testing is not recommended, except in patients with serious risk factors such as dysphagia, protracted vomiting, anorexia, melena, anemia, or a palpable mass. In these patients, endoscopy should be considered to exclude gastroesophageal reflux disease, peptic or duodenal ulcer, and gastric cancer. In patients without risk factors, consideration should be given to empiric therapy with a prokinetic agent (e.g., metoclopramide), an acid suppressant (histamine-H2 receptor antagonist), or an antimicrobial agent with activity against Helicobacter pylori. Treatment of patients with H. pylori infection and nonulcer dyspepsia (rather than peptic ulcer) is controversial and should be undertaken only when the pathogen has been identified. Psychotropic agents should be used in patients with comorbid anxiety or depression. Treatment of nonulcer dyspepsia can be challenging because of the need to balance medical management strategies with treatments for psychologic or functional disease.     

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.     

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.     

Efficacy of omeprazole plus two antimicrobials for the eradication of Helicobacter pylori in a Turkish population.

Omeprazole combined with 2 antimicrobials has been suggested as a first-line option for Helicobacter pylori eradication in recent years. However, controversy exists regarding the efficacy of this protocol. This open-label, prospective clinical study investigated the efficacy of omeprazole-based triple therapy for H pylori eradication in 518 patients with H pylori-positive functional dyspepsia with or without duodenal ulcer. Amoxicillin, macrolides (clarithromycin or roxithromycin), and nitroimidazoles (metronidazole, ornidazole, or tinidazole) were the antibiotics used in the study. Nonulcer patients were randomly assigned to 1 of 8 different treatment protocols and duodenal ulcer patients were randomly assigned to 1 of 4 different treatment protocols consisting of omeprazole (20 mg once daily for nonulcer patients, 20 mg twice daily for ulcer patients for 14 days) with a combination of 2 of the above antimicrobials (for 10 days). H pylori infection was assessed by histologic findings and a rapid urease test before therapy and 4 weeks after therapy ended. Four hundred fifty-nine patients completed their regimens; 327 had functional dyspepsia (180 men, 147 women; median age, 39 years; range, 18 to 70 years) and 132 had ulcers (81 men, 51 women; median age, 40 years; range, 18 to 70 years). Eradication of H pylori was achieved in 58.8% (270 of 459) of all patients, 58.1% (190 of 327) of nonulcer dyspeptic patients, and 60.6% (80 of 132) of duodenal ulcer patients. The eradication rate varied from 47.2% to 69.4% in different treatment protocols. There were no statistically significant differences in eradication rates in any treatment group. All drugs were generally well tolerated in all groups, and no patient discontinued treatment because of side effects. Therapy with omeprazole and 2 antimicrobials for H pylori had limited efficacy in a Turkish population. The reason for these results, which conflict with those of other studies, is not clear. Further investigations of regimens for the eradication of H pylori in our population are necessary.     

Campylobacter gastritis and associated disorders

Our review of evidence that Campylobacter pylori is an important factor in gastritis, peptic ulcer disease, and "nonulcer dyspepsia" suggests that C pylori is the most common cause of chronic active gastritis. The association between C pylori gastritis and duodenal ulcer, which approaches 100%, leads to the suggestion that this infection plays an important role in the pathogenesis of duodenal ulcer. Evidence supporting a central role in the pathogenesis of gastric ulcer and nonulcer dyspepsia is less compelling.     

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.     

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.     

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.     

幽门螺杆菌感染的危害和防控

幽门螺杆菌（HP）感染是人类最常见的慢性感染之一，目前我国人群中的HP感染率仍高达40%～50%。HP感染者几乎均会发生慢性活动性胃炎，部分感染者可发生消化性溃疡、消化不良，少数感染者可发展至胃癌，HP感染是胃部疾病的罪魁祸首。此外，HP感染与不明原因缺铁性贫血、特发性血小板减少性紫癜等胃外疾病的发病密切相关。根除HP对HP感染相关疾病的治疗和预防起重要作用。HP感染可通过口-口、粪-口和胃-口途径在人-人之间传播；HP主要在家庭内传播；改变不良卫生习惯可减少其传播。     

Helicobacter pylori: aggressor or innocent bystander?

Helicobacter pylori seeks gastric mucosa, whether found in the stomach, duodenum, or Barrett's esophagus. Definitive diagnosis can be secured by appropriate stains of mucosal biopsies and culture, but the rapid urease test, breath isotope studies, and serologic testing are also useful. The frequency of colonization increases with advancing age, but infection occurs earlier in underdeveloped countries. Although the reservoir is uncertain, water or food transmission seems likely. There is sufficient evidence to assign an etiologic role to the bacteria in the causation of type B antral gastritis. H. pylori is found in areas of gastric metaplasia within the duodenum and is associated with duodenitis. Although acute infection leads to hypochlorhydria, chronic colonization has little effect on acid secretion. Studies have thus far failed to establish a convincing relationship between H. pylori and nonulcer dyspepsia, although the bacteria may play a role in selected patients. H. pylori is found in association with most idiopathic gastric and duodenal ulcers, but it is unclear as to whether the bacteria plays a causative or permissive role. The organism has a predilection for intercellular spaces and the mucous layer, thus affording relative isolation from luminally active antibiotics. Monotherapy with bismuth preparations transiently eliminates the bacteria, but recolonization is rapid, probably due to regrowth of sequestered organisms. A combination of metronidazole, bismuth, and tetracycline (or amoxicillin) affords the best eradication rate, but the potential side effects of this program should be considered. The present therapy of duodenal ulcer disease is effective and without significant risk. Treatment of H. pylori should be reserved for those patients who relapse on adequate maintenance therapy. If a safe and effective antibiotic becomes available, more frequent testing and earlier treatment intervention may become more attractive. H. pylori is probably an "innocent bystander" for most patients, but the bacteria may sufficiently impair the defenses of the antral and duodenal mucosa to facilitate the development and relapse of ulcer disease in subsets of patients.     

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.     

根除幽门螺杆菌治疗功能性消化不良的临床证据

目的为临床实践提供有关功能性消化不良(FD)根除幽门螺杆菌(HP)治疗的循证医学证据。方法根据HP感染与FD的关系和HP根除治疗在治疗FD中的作用两个临床问题,检索VIP(1989～2005)、CBMdisc(1978～2005)、MEDLINE (1978～2006)以及Cochrane图书馆(2005年第4期)的系统评价,Meta分析,随机对照试验和临床指南,评价HP感染与FD的关系和HP根除治疗在治疗FD中的作用,为临床实践提供最佳的循证医学证据。结果共纳入2篇系统评价、1篇Meta分析和11篇随机对照试验。现有证据显示:FD患者HP感染率高于无症状者,但HP感染在FD发生中的作用还有待流行病学研究及病理生理研究的证据证实。HP根除治疗HP阳性FD,可以减缓部分消化不良患者的症状,但对改善患者生活质量无明显意义。HP根除治疗的成本-效益价值主要取决于患者希望明确诊断的愿望,还没有很好地证据显示需要对HP阳性FD都行HP根除治疗。结论基于目前的临床证据,我们认为对FD是否行HP根除治疗应根据患者的情况,做到个体化,对一些常规治疗差的患者可考虑采用HP根除治疗。     

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.     

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.     

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.     

中国幽门螺杆菌感染的现状

我国是幽门螺杆菌（HP）高感染地区，HP感染相关疾病负担（尤其是胃癌）较重，国内学术界应尽快统一认识，重视HP感染的危害，建立有效的胃癌一、二级预防体系；同时，随着近年来抗生素耐药率的不断上升，传统方案根除率逐年下降，临床医师应参照最新共识，规范HP感染的诊治，重视提高初次HP根除率。