Helicobacter pylori infection and its role in human disease — an overview

Helicobacter pylori (H. pylori) is probably the commonest chronic bacterial infection in humans. The bacterium colonizes the gastric epithelium and induces inflammation of the underlying mucosa. The recognition that this infection is the most important acquired factor in the pathogenesis of duodenal and gastric ulcers has transformed the management of these common disorders. Most patients with ulcers can be cured by a 1-week course of anti-H. pylori therapy, thereby removing the need for long-term acid inhibitory therapy. Eradication of the infection involves taking complex combinations of drugs and simpler eradication regimens are required. Recent epidemiological data indicate an association betweenH. pylori infection and the subsequent development of gastric carcinoma. If this association is established as causal, then widespread eradication of the infection may be indicated. Global eradication ofH. pylori will probably rely on prophylactic or therapeutic vaccination and this approach is being actively investigated.     

Review article: Helicobacter pylori and NSAID gastropathy

Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori are known to share a number of pathogenic mechanisms, but there is no evidence to show a significant synergic action between the two risk factors. Studies assessing this subject have differed in almost every aspect of their methodology, including the definition of a NSAID user as well as the types, doses, duration and their indications for NSAID use. They also differed in their end-points, the definition of dyspepsia and the regimes used for eradication of H. pylori. However, some conclusions may be drawn from the results of clinical trials. In H. pylori-positive patients without mucosal lesions, NSAIDs may aggravate dyspeptic symptoms but, with the exception of elderly patients, they do not present a definite major risk of gastric and duodenal lesions and, above all, of ulcer-correlated complications. So what recommendations can be made with regard to H. pylori eradication in patients requiring treatment with NSAIDs? The microorganism and the anti-inflammatory drugs are undoubtely independent causes of gastric and duodenal damage. Patients taking NSAIDs who are found to have gastric or duodenal ulcers should therefore be tested for the bacterium and specifically treated, since H. pylori and NSAID-induced ulcers may be macroscopically indistinguishable. Whether asymptomatic patients taking NSAIDs should be tested and treated for H. pylori infection is still a matter of debate.     

Treatment of Helicobacter pylori in Special Patient Populations

Helicobacter pylori infection can lead to gastritis, gastric and duodenal ulcers, and gastric cancer. Consequently, complete eradication is the goal of therapy. First-line therapy for H. pylori infection includes clarithromycin triple therapy (clarithromycin, proton pump inhibitor [PPI], and amoxicillin or metronidazole), bismuth quadruple therapy (bismuth salt, PPI, tetracycline, and metronidazole or amoxicillin), or concomitant therapy (clarithromycin, PPI, amoxicillin, and metronidazole). However, many patients have relative contraindications to the antibiotics included in these regimens, making therapy selection difficult. Furthermore, failure of initial therapy makes selection of second-line therapy challenging due to concerns for potential resistance to agents included in the initial regimen. This review discusses H. pylori microbiology, including antibiotic resistance, and summarizes the existing evidence for first- and second-line treatment regimens that may be considered for special populations such as patients with penicillin allergies, patients with or at risk for QTc-interval prolongation, and patients who are pregnant, breastfeeding, or elderly.     

Helicobacter pylori infection in peptic ulcer haemorrhage

In this overview, medical advice for routine clinical practice regarding peptic ulcer haemorrhage (PUH) is given, based on the extensive literature about Helicobacter pylori and the controversial results about the interaction of H. pylori infection and nonsteriodal anti-inflammatory drug (NSAID) use. PUH remains an important emergency situation with an incidence between 32 and 51/100 000 persons per year. There is a high association between H. pylori infection and peptic ulcer disease. The association between H. pylori infection and PUH is less clear, but a strong argument for the aetiological role is the fact that eradication of H. pylori decreases recurrence of bleeding. NSAID use is another important risk factor for PUH. H. pylori infection and NSAID use seem to act independently, although some studies show a synergistic interaction while other studies report that H. pylori is protective against the development of PUH in NSAID users. All patients with PUH should be tested for H. pylori infection, regardless of the use of NSAIDs. Because invasive tests are less sensitive in PUH patients, negative tests in patients with no other risk factors should be confirmed by serology or urea breath test (UBT). Eradication therapy with a proton pump inhibitor or ranitidine bismuth citrate-based triple therapy should be given to all H. pylori- positive patients. Only for nonaspirin–NSAID users does the effect of eradication therapy on the healing of gastric ulcers remain controversial, but currently we also advise eradication of H. pylori in this subgroup. After eradication therapy, acid-suppressant therapy is advised to heal the ulcer. The success of eradication should always be confirmed because of the risk of recurrence of peptic ulcer disease and bleeding in H. pylori- infected patients.     

clinical aspects of Helicobacter pylori eradication therapy in peptic ulcer disease

Background and aims : Although the role of H. pylori in peptic ulcer disease is no longer in dispute, certain aspects of eradication therapy in this condition have yet to be settled. Uncertainties still surround the relationship between Helicobacter pylori status and ulcer healing, the efficacy of eradication therapy in alleviating acute symptoms and healing ulcers, and the prognosis after eradication with respect to recurrence of symptoms, ulcers and complications. The present literature review, encompassing studies published up to October 1995, specifically addresses these issues.
Results : Pooled data show that eradication therapy heals 90% of duodenal ulcers and 85% of gastric ulcers, while individual studies repeatedly confirm that it is more effective at healing ulcers than conventional treatment with anti-secretory drugs. Recent reports indicate that triple therapy regimens for 1 week, provided they include an anti-secretory drug, are sufficient to achieve high rates of healing and rapid symptom relief. A detailed analysis of the data, particularly those from studies reporting healing rates in relation to H. pylori status after eradication therapy, provides strong evidence that eradication of H. pylori produces ulcer healing. Follow-up studies show that ulcer recurrence and complications are rare after eradication treatment in patients with either gastric or duodenal ulcer disease. However, while ulcer symptoms are infrequent during follow-up, a proportion of patients appear to develop gastrooesophageal reflux after eradication.
Conclusions : H. pylori eradication is highly effective in promoting ulcer healing and preventing subsequent ulcer recurrence. These beneficial effects of eradication therapy are observed in patients with either gastric or duodenal ulcers which are associated with H. pylori infection.     

The Role of Helicobacter pylori in Peptic Ulcer Disease

The pathophysiology of peptic ulcer disease (PUD) is often described as an imbalance between aggressive factors such as acid and pepsin and alterations in the mucosal protective mechanisms. Helicobacter pylori is a gram-negative organism that has been identified as a potential causative agent in the pathogenesis of PUD. The exact mechanism by which it contributes to mucosal damage is unknown. It is thought that the organism may disrupt the protective mucous layer, allowing the underlying epithelium to be injured by gastric acid. Significant evidence indicates that H. pylori is a major etiologic factor in type B gastritis. Data confirming its etiologic role in duodenal ulcer (DU) disease is not conclusive; however, eradication of the organism is associated with a reduction in the recurrence of DU. Optimum therapy to eradicate H. pylori has not been established, although several multidrug regimens have been evaluated. Treatment of H. pylori infection should be reserved for individuals in whom conventional therapy for DU is unsuccessful and those whose ulcers relapse during maintenance therapy.     

Review article: common misconceptions in the management of Helicobacter pylori-associated gastric MALT-lymphoma

Aliment Pharmacol Ther 2011; 34: 1047–1062

Summary

Background Helicobacter pylori infection is the main cause of gastric mucosa‐associated lymphoid tissue (MALT) lymphoma. Aim To review several common misconceptions in the management of H. pylori‐associated gastric MALT‐lymphoma. Methods Bibliographical searches were performed in MEDLINE up to June 2011. Results If adequate diagnostic methods are used, and if only low‐grade lymphomas are considered, the prevalence of H. pylori infection is very high (almost 90%). H. pylori eradication is effective in treating approximately 80% of patients with early stage lymphoma. In H. pylori‐positive gastric high‐grade lymphomas, antibiotic therapy should always be prescribed, as approximately 50% of them regress after H. pylori eradication. Patients with early stage MALT lymphoma negative for H. pylori might still benefit from antibiotic treatment as the sole treatment. Complete remission of gastric MALT lymphoma after H. pylori eradication can take even >12 months. PCR assay for the detection of monoclonal B cells remains positive in many cases after complete remission has been reached. Patients with a persistent clonal band should not be treated unless the lymphoma can be histologically demonstrated. Synchronous occurrence of gastric adenocarcinoma and MALT lymphoma has been repeatedly reported. In some patients in complete remission, eradication of H. pylori does not prevent later development of early gastric cancer. Gastric lymphoma recurrence occurs in some patients after both bacterial and lymphoma regression. H. pylori reinfection does not constitute a prerequisite for lymphoma recurrence. Conclusions The present article states several misconceptions in the management of H. pylori‐associated gastric MALT‐lymphoma in clinical practice, reviews the related scientific evidence and proposes the adequate attitude in each case.     

Effect of bacterial and host factors on Helicobacter pylori eradication therapy

Introduction: A clearer understanding of the factors affecting the cure rate of Helicobacter pylori infection might lead to the development of novel prevention strategies and therapeutic targets.

Areas covered: This review covers two important issues that affect the eradication of H. pylori: bacterial and host factors. Several virulence factors have been shown to be predictors for gastroduodenal diseases. Successful treatment of H. pylori infection also depends on host genetic factors such as CYP2C19 and IL-1B. The latest evidence on host genetic factors is discussed.

Expert opinion: The authors identify three main targets for achieving effective eradication therapy. The first therapeutic target is to identify counter measures for antibiotic-resistant H. pylori strains. Thus, antibiotic susceptibility should be checked in all patients, ideally, before the start of eradication treatment. The second therapeutic target is the inhibition of acid suppression. Maintaining a high intragastric pH for 24 h increases the effectiveness of some antibiotics and the eradication effects for H. pylori. The third therapeutic target is to identify high-risk groups; the CYP2C19 and IL-1B polymorphisms are candidates for significant risk factors. A personalized medical approach will likely increase the cure rate of H. pylori infection.     

Review article: Helicobacter pylori infection in peptic ulcer haemorrhage

In this overview, medical advice for routine clinical practice regarding peptic ulcer haemorrhage (PUH) is given, based on the extensive literature about Helicobacter pylori and the controversial results about the interaction of H. pylori infection and nonsteriodal anti-inflammatory drug (NSAID) use. PUH remains an important emergency situation with an incidence between 32 and 51/100 000 persons per year. There is a high association between H. pylori infection and peptic ulcer disease. The association between H. pylori infection and PUH is less clear, but a strong argument for the aetiological role is the fact that eradication of H. pylori decreases recurrence of bleeding. NSAID use is another important risk factor for PUH. H. pylori infection and NSAID use seem to act independently, although some studies show a synergistic interaction while other studies report that H. pylori is protective against the development of PUH in NSAID users. All patients with PUH should be tested for H. pylori infection, regardless of the use of NSAIDs. Because invasive tests are less sensitive in PUH patients, negative tests in patients with no other risk factors should be confirmed by serology or urea breath test (UBT). Eradication therapy with a proton pump inhibitor or ranitidine bismuth citrate-based triple therapy should be given to all H. pylori-positive patients. Only for nonaspirin-NSAID users does the effect of eradication therapy on the healing of gastric ulcers remain controversial, but currently we also advise eradication of H. pylori in this subgroup. After eradication therapy, acid-suppressant therapy is advised to heal the ulcer. The success of eradication should always be confirmed because of the risk of recurrence of peptic ulcer disease and bleeding in H. pylori-infected patients.     

Pharmacological study on the pathological changes of the gastric mucosa in Helicobacter pylori-infected Mongolian gerbils]

Helicobacter pylori (H. pylori) infection has been recognized to be a causal factor of gastritis, ulcers and gastric cancer in man. Using Mongolian gerbils (M. gerbils), which are suitable for an H. pylori infection animal model, we examined 1) how H. pylori infection, indomethacin and their combination affects the healing of gastric ulcers and whether or not such factors provoke a relapse of healed acetic acid ulcers; and 2) whether or not eradication of the bacteria with drugs at specified times after infection prevents the development of mucosal changes, including gastric adenocarcinoma. 1) H. pylori infection significantly delayed ulcer healing 4 weeks following infection. Indomethacin treatment showed a tendency to delay ulcer healing. Ulcer healing in H. pylori-infected M. gerbils was significantly delayed by indomethacin. H. pylori infection resulted in a relapse of healed ulcers from 1 to 6 months after infection, with a gradual increase in size. Omeprazole markedly prevented the ulcer relapse caused by H. pylori infection. 2) Four or 8 months after H. pylori inoculation, eradication was performed by concurrent treatment with omeprazole + clarithromycin. Immediately after treatment ended in both the 5 and 9 month groups, it was verified that H. pylori were completely eradicated. Autopsy performed 18 months after H. pylori inoculation revealed gastric hyperplastic polyps with erosive lesions and ulcers that were grossly visible; and atrophic gastritis, intestinal metaplasia, carcinoids, and adenocarcinomas were histologically observed in the non-treated control group. In animals eradicated after 4 months and autopsied after 18 months, however, such mucosal changes were not observed. In contrast, intestinal metaplasia and mucosal atrophy was observed in animals eradicated after 8 months and autopsied after 18 months. It was concluded that 1) H. pylori infection delayed the healing of preexisting gastric ulcers and resulted in the relapse of healed ulcers, yet indomethacin had little or no effect on ulcer healing or relapse; and 2) early eradication of H. pylori infection with drug therapy can prevent severe gastric mucosal changes, to include adenocarcinomas, in M gerbils.