Abstract & Commentary
Synopsis: Helicobacter pylori is an exceedingly common inhabitant of the human stomach. The discovery of its role in the pathogenesis of peptic ulcer disease was revolutionary, but many questions remain about this organism and an appropriate medical approach to its presence.
Source: Suerbaum S, Michetti P. N Engl J Med. 2002; 347(15):1175-1186.
Helicobacter pylori was first cultured 20 years ago, and it was soon recognized that peptic ulcer disease might have an infectious pathogenesis. Presence of the organism is strongly correlated with socioeconomic conditions, ranging from 80% of middle-aged adults in developing countries to as little as 20% in industrialized countries. It seems likely that the decreased infection levels in the United States will eventually lead to the complete elimination of this infection from our society. H pylori in adults is usually chronic and resolves only with specific therapy, but children probably commonly spontaneously eliminate this infection. H pylori survives in the stomach using a number of protective mechanisms, including the production of urease-generated ammonia as a potent acid-neutralizing agent. Gastric inflammation is invariably produced by infestation with H pylori, and some infected patients have an autoantibody against the ATP-ase of parietal cells that may lead to gastric atrophy. Clinical outcome of infection is highly variable. Antral gastritis is associated with duodenal ulcers, and corpus gastritis seems related to gastric ulcers, gastric atrophy, intestinal metaplasia, and potentially gastric adenocarcinoma. MALT lymphoma is directly related to H pylori infection in genetically susceptible individuals. Incidence of cancer in Japan has been documented at 2.9% over 8 years. Nevertheless, it remains clear that most patients with H pylori infection never get ulcers, malt lymphoma, or gastric cancer. Controversy continues as to whether infection with H pylori protects against gastroesophageal reflux disease. Diagnostic tests for infection include the urea breath test, serological tests, and stool antigen testing. Serology cannot document either active infection or effective eradication. Trials have documented the substantial efficacy of triple therapy with PPI (b.i.d. except for rabeprazole that can be administered once daily) and 2 antibiotics (usually clarithromycin and amoxicillin) for H pylori eradication. Failure of eradication is common, often due to poor compliance with the initial regimen and may require quadruple therapy including a bismuth-based triple regimen plus a PPI or H2 receptor antagonist. Rifabutin plus amoxicillin and a PPI might be another option for second-line therapy. At the moment, the only completely accepted indications for H pylori eradication are ulcer disease and MALT lymphoma. Except in settings with a known high background prevalence of ulcer disease, empirical treatment of H pylori in dyspeptic patients is not recommended.
Comment by Malcolm Robinson MD, FACP, FACG
This area remains confusing, partly because many medical payers have urged empirical treatment of H pylori for economic reasons. The strong epidemiologic data for an inverse relationship between the presence of H pylori and gastroesophageal reflux disease would certainly suggest that physicians avoid seeking to diagnose H pylori in patients with primary GERD symptoms.
Strong international recommendations for aggressive eradication of H pylori to prevent cancer probably do not apply to North America.
Dr. Robinson, Medical Director, Oklahoma Foundation for Digestive Research; Clinical Professor of Medicine, University of Oklahoma College of Medicine Oklahoma City, OK, is Associate Editor of Internal Medicine Alert.