KEY POINTS■ Helicobacter pylori infection leads to infl ammation of the gastric mucosa and damage to the gastric epithelium. Gastritis reduces hydrochloric acid production, and the extent of acid-production loss is directly related to the risk of developing gastric cancer. While the bacterium is not a direct cause of cancer, its presence and the resultant reduction in acid production are necessary factors in causation.
■ Most guidelines recommend triple therapy with a proton pump inhibitor, clarithromycin, and either amoxicillin or metronidazole. The addition of a bismuth-containing medication to this regimen is also recommended as first-line therapy. Duration of treatment varies with the regimen but is usually 7 to 14 days.
■ Sequential therapy consists of a PPI and a single antibiotic, typically amoxicillin, for 5 days, followed by triple therapy with a PPI, a macrolide, and an imidazole for 5 days. Sequential therapy was proven to be superior to standard regimens in treatment-naïve patients.
Peptic ulcer disease was once believed to be caused by stress or dietary indiscretions.1 Treatment included hospitalization for bed rest, a bland diet, and antacids to reduce stomach acids. Gastric acid was seen to play an important role in the pathogenesis of ulcer disease; therefore, antacids and drugs that reduce acid production became the treatments of choice. However, treatment response was temporary at best because recurrence rates were high, and ulcers often returned when treatment was stopped. Surgery to remove the ulcers or a vagotomy to reduce acid secretion was recommended for refractory or complicated cases.
EPIDEMIOLOGY
At least 100 years ago, microorganisms were noted to overlie the gastric mucosa.1 In 1983, Marshall and Warren2 were able to culture these organisms and identified Helicobacter pylori as the cause of 95% of duodenal ulcers and 70% of gastric ulcers.3H pylori bacteria are transmitted by the fecal-oral route, usually in childhood.4 The prevalence of infection is inversely related to the quality of household and public sanitation, and entire families becoming infected with the organism is not uncommon.1 Infection rates in developing countries approach 80%, whereas the infection rate in the United States is about 30%.5 Incidence in the United States also varies between racial and ethnic groups and comprises 26% of whites, 50% of African-Americans, and 60% of Mexican Americans.1 Colonization with H pylori does not result in disease in all cases, as disease that requires treatment will develop in only 10% to 20% of infected persons.
PATHOPHYSIOLOGY
H pylori is a motile, flagellated, gram-negative, spiral bacterium. It survives in the acid environment of the stomach by producing urease, which converts urea to ammonia thereby generating localized areas of acid neutralization.4 Other virulence factors include proteins that allow the bacteria to adhere to organ cells and resist eradication; a vacuolization cytotoxin A that promotes cell membrane dysfunction and immunomodulation; and the microorganism's cytotoxin-associated gene pathogenicity island, which produces an increased inflammatory response that elevates the risk for peptic ulcers and gastric cancer.6
H pylori infection leads to inflammation of the gastric mucosa and damage to the gastric epithelium.1,6 Gastritis reduces hydrochloric acid production, and the extent of acid-production loss is directly related to the risk of developing gastric cancer. While the bacterium is not a direct cause of cancer, its presence and resultant reduction in acid production are necessary factors in causation. The chronic inflammation induced by H pylori infection, in conjunction with genetic susceptibilities in the host, is the likely cause of intestinal metaplasia. The risk of developing cancer is proportionate to the duration of atrophic gastritis.5 Treating H pylori infection reduces this risk by reversing the gastritis. Endoscopic examination is recommended to document the presence of atrophic gastritis and intestinal metaplasia.
H pylori 's role in gastroesophageal reflux disease (GERD) is not clear.1 Current evidence indicates that H pylori does not cause GERD or influence treatment response. However, eradication of H pylori restores acid production and may result in symptomatic GERD in patients who were protected from symptoms by the reduced acid production.