Helicobacter pylori infects half of the world's population, with an estimated prevalence in the United States of 30%.[1] Prevalence of the infection appears to be declining in the general population, but it is more common in low socioeconomic and immigrant populations. The reported prevalence is higher in some ethnic groups, including African Americans, Asians, and Hispanics.[1] Two decades have passed since H pylori was discovered. Knowledge about this gastric bacterium has evolved from total disbelief that it could be associated with gastrointestinal tract disease to the recognition that it is the most common cause of peptic ulcer disease. H pylori has been classified as a Group 1, or definite, carcinogen by the World Health Organization. How this infection causes gastric inflammation and its precise role(s) in peptic ulcer and gastric malignancy continue to be actively investigated. The human host is the only known reservoir. The infection is most likely acquired in childhood. Transmission occurs by person-to-person contact, by both fecal-oral and oral-oral routes.
The issue is not "Whom should we treat?" but "Which patients should be tested for H pylori?" Patients should not undergo testing unless treatment for a positive test is planned. Antibiotic treatment for H pylori eradication should be offered to all patients with a positive test result. If antibiotic treatment is not selected, the patient should be aware of potential severe clinical outcomes, such as increased risk for peptic ulcer or gastric malignancy. Helpful management guidelines have been published.[2]
H pylori infection should be confirmed before eradication therapy. Accurate, cost-effective tests to diagnose the infection are now commercially available. Tests that do not require endoscopy include the blood antibody test, the urea breath test, and the stool antigen test. If the patient is undergoing endoscopy, gastric tissue can be obtained for the biopsy urease test or for histology. Culture is not recommended for routine diagnosis because H pylori infection is difficult to culture.
The most common causes of peptic ulcer are H pylori infection and nonsteroidal anti-inflammatory drug (NSAID) use. A nested, case-control study in Japanese-American men reported that the odds ratios for gastric ulcer and duodenal ulcer in the setting of H pylori infection were 3.2 and 4.0, respectively.[3] If H pylori infection is eradicated, ulcer recurrence is low. Laine and colleagues[4] showed that ulcer recurrence was 19.6% at 6-month follow-up if the infection was eradicated, compared with 55% ulcer recurrence in those patients remaining infected.
H pylori infection and NSAID use are probably independent risk factors for ulcer development. A meta-analysis by Huang and colleagues[5] showed that H pylori infection and NSAID use each increased the risk of peptic ulcer disease. When both risk factors were present, there was at least an additive increased risk. Patients with a history of ulcer disease should be tested for H pylori infection; if the test is positive, antibiotic treatment should be prescribed. There is some discussion that patients with significant NSAID-related ulcer risk factors should be tested for H pylori prior to beginning chronic NSAID use, but currently there are no guidelines regarding this issue.
Hpylori infection is detected in over 90% of patients with gastric MALT (mucosa-associated lymphoid tissue) lymphoma.[6] Eradication of the infection resulted in complete disease regression in 50% and partial regression in an additional 29% of patients in a US study of gastric MALT lymphoma patients.[7] The Helicobacter and Cancer Collaborative Group reported an overall odds ratio of 2.8 for the association between H pylori infection and gastric adenocarcinoma.[8] Uemura and colleagues[9] followed 1526 patients in Japan for 8 years with endoscopic evaluations, confirming the association of infection and development of gastric cancer. Of patients infected with H pylori, 2.9% developed cancer during this study period while no patients without H pylori infection developed gastric cancer. Correa and colleagues[10] performed an intervention trial with H pylori eradication with or without antioxidants in a South American population with gastric cancer histologic precursor lesions. Significant regression of lesions was not seen in any arm of the study. Follow-up studies will determine whether progression of these lesions is prevented. Eradication of H pylori infection can reverse gastric MALT lymphoma, but it is unlikely to reverse gastric premalignant lesions related to gastric adenocarcinoma, such as atrophic gastritis and intestinal metaplasia.
The role of H pylori infection in dyspepsia has been unclear. A Canadian multicenter study evaluated symptom improvement/resolution in H pylori-infected patients with uninvestigated dyspepsia at 1 year after randomization to H pylori therapy or a proton-pump inhibitor (PPI) with placebo.[11] Significantly more patients (50%) in the eradication-therapy group had no or minimal symptoms at 1 year vs 36% in those randomized to PPI with placebo (P = .02) with a number needed to treat of 7 (95% confidence interval, 4-63). However, a large population-based community screening study in the United Kingdom found only a modest 5% reduction in dyspepsia with no impact on quality of life at a 2-year follow-up period in patients randomized to H pylori treatment compared with placebo.[12] Benefit of H pylori eradication likely depends on prevalence of the infection and peptic ulcer disease in a population. A meta-analysis of prospective, randomized studies with at least 1 year of follow-up examined the possible benefit of H pylori eradication in nonulcer dyspepsia.[13] There was a statistically significant benefit of H pylori eradication compared with patients randomized to placebo or a PPI, but again the therapeutic gain was a very modest 5%. Patients with nonulcer dyspepsia should be managed on a case-by-case basis.
The role of H pylori in gastroesophageal reflux disease (GERD) remains a topic of much discussion. A study from Kuipers and colleagues[14] suggested that chronic PPI use in patients with GERD might increase risk of gastric premalignant atrophic gastritis and intestinal metaplasia in H pylori-infected patients. This has not been confirmed in other studies. Lundell and colleagues[15] showed that H pylori infection -- and not the PPI -- was the inciting factor that caused progression of precursor lesions. The prevalence of H pylori infection in GERD is similar to that in the general population. While several studies show an inverse relationship between H pylori infection and esophageal disorders including Barrett's esophagus and esophageal adenocarcinoma, no causal relationship has been identified.[16] GERD and H pylori infection are likely to be independent upper gastrointestinal tract conditions.
Several studies have suggested that some patients may develop new GERD or worsening GERD after H pylori eradication. Two US studies have shown that H pylori eradication in the patient with duodenal ulcer does not lead to a statistically significant increase in the development of GERD or exacerbation of preexisting GERD.[17,18] Laine and Sugg[18] conducted a post hoc analysis of US clinical trials of patients with duodenal ulcer disease who underwent H pylori eradication treatment. There was no statistically significant increase in the number of patients with GERD symptoms or erosive esophagitis. There was a small increased likelihood of worsened GERD when H pylori infection was not eradicated (P = .02). There are no current indications for testing for H pylori in the patient with GERD alone. The patient with an active or past history of peptic ulcer disease should be tested for H pylori infection, irrespective of GERD status.
Effective multidrug combinations to eradicate H pylori infection have been approved by the US Food and Drug Administration. One regimen includes twice-daily amoxicillin 1 gm, clarithromycin 500 mg, and a PPI (lansoprazole 30 mg, rabeprazole 20 mg, or omeprazole 20 mg).[19,20] The PPI in this regimen can be replaced with once-daily esomeprazole 40 mg with similar efficacy.[21] These regimens have been approved for 10-day treatment. Twice-daily rabeprazole with twice-daily amoxicillin and clarithromycin therapy was recently approved for 7-day treatment for H pylori eradication to prevent duodenal ulcer recurrence.[22] The second regimen includes Pepto-Bismol (2 tablets), metronidazole 250 mg, and tetracycline 500 mg 4 times daily for 14 days in conjunction with a daily antisecretory agent (preferably a PPI) for 4-6 weeks. Eradication rates for all of these approved regimens were 85% to 90%. Lower eradication rates occur if patients are noncompliant or if H pylori antibiotic resistance is present.
In summary, H pylori eradication is indicated in patients with peptic ulcer disease or gastric MALT lymphoma. Whether gastric cancer precursor lesions can be reversed with H pylori eradication remains to be confirmed. There is general consensus that H pylori should be eradicated in first-degree relatives of gastric cancer patients. A small number of patients with uninvestigated dyspepsia will achieve long-term symptom improvement. Eradication of the infection in nonulcer dyspepsia will yield only a modest long-term benefit, but indications in these patients should be based on an individual basis. H pylori infection remains the most common cause of peptic ulcer disease, but the continuing increase in NSAID use makes it important that NSAIDs also be considered in the etiology of ulcers. The patient infected with H pylori and taking chronic NSAIDs has a greater risk of peptic ulcer compared with the patient with only 1 of these risk factors. There is little concern about GERD development or exacerbation after H pylori eradication.
Medscape Gastroenterology. 2003;5(2) © 2003 Medscape
Cite this: Helicobacter pylori: When to Test and How to Treat - Medscape - Sep 10, 2003.
