Managing patients infected with H. pylori
A peptic ulcer (white) is formed when stomach acid and bacteria irritate the lining of the stomach.
The American College of Gastroenterology has published its Guideline on the Management of Helicobacter pylori Infection, the organization's first set of official recommendations since 1998. In the past decade, “a significant amount of new information…has become available,” the authors say.
Helicobacter pylori infection is widespread (U.S. prevalence is estimated at 30%-40%), and although it has no clinical manifestations in most infected individuals, the organism can be associated with significant GI pathology, notably peptic ulcer disease (PUD), chronic gastritis, and gastric malignancy.
Whom to test
The indications for testing and treatment “haven't changed much,” says author William D. Chey, MD, professor of medicine at University of Michigan, Ann Arbor. PUD is still an “absolute indication.” With regard to gastric mucosa-associated lymphoid tissue (MALT) lymphoma, evidence to support treatment of H. pylori “is much stronger than it was in 1998,” he observes; new data suggest that eradication can provide lasting remission in a substantial number of patients with high-grade as well as low-grade tumors.
A change of particular interest to primary-care practitioners is the firm recommendation to test for and treat H. pylori infection in patients with uninvestigated dyspepsia who are younger than 55 years and don't have “alarm features,” such as bleeding, anemia, or unexplained weight loss.
Although the test-and-treat approach is “evidence-based,” clinicians should be mindful of its limitations. “The strategy works better than placebo, but while 30%-40% of people will get better, the majority will not,” Dr. Chey says. “Doctors' and patients' expectations need to be aligned with reality. The point is that it works better than nothing at all.”
The cost-benefit argument—this strategy reduces the number of endoscopies and office visits—depends on demographics: The advantage is clear when H. pylori prevalence is >20%, as in populations that include substantial numbers of African Americans, Asians, and Eastern European immigrants. As many as 80%-90% of such individuals are likely to be infected, compared with 10%-15% of American-born Caucasians.
The Guideline lists other contingencies in which the benefits of eradicating H. pylori remain controversial. New data suggest an association between unexplained iron deficiency and infection, although no causal relationship has been established. The connection is biologically plausible: PUD may be accompanied by microscopic blood loss; chronic H. pylori infection may lead to acid hyposecretion, which compromises iron absorption; the organism competes with the host for iron.
“The epidemiological association is based on circumstantial evidence, and we can't make a formal recommendation,” Dr. Chey says. “But if a patient has unexplained iron deficiency, in addition to testing for celiac disease, I'll test for H. pylori.”
The utility of eradicating H. pylori to reduce gastric adenocarcinoma risk is similarly unclear. The organism is classified as a carcinogen by the World Health Organization, and there are data that its eradication is “protective” against progression of premalignant gastric lesions. Some studies from regions where gastric cancer is prevalent (but not where it is rare, such as the United States) suggest that H. pylori eradication may also lower risk in the absence of such lesions.
Helicobacter pylori testing for an individual whose ethnic background or family history suggests a high risk of gastric cancer might be considered “on a case-by-case basis,” Dr. Chey says.
How to test
The Guideline notes that none of the available endoscopic and nonendoscopic testing options “can be considered the gold standard” and recommends choice based on clinical indications, infection prevalence, availability, and cost. In the primary-care setting, this nearly always comes down to one of the nonendoscopic procedures: antibody testing, urea breath test (UBT), or fecal antigen test (FAT).
“In practice, most clinicians tend to do serology: Testing is cheap and widely available, and its negative predictive value is good,” Dr. Chey says. “The bad news is that the positive predictive value is terrible.” In areas where prevalence is low (e.g., 20% or below), the Guideline points out, a positive finding in a patient with dyspepsia is “no better than a coin toss.”
UBT and FAT are considerably more accurate. Particularly where prevalence is low, these should be chosen at the outset if readily available or done to confirm a positive antibody test, Dr. Chey says.
Clinicians should remember that the accuracy of UBT and FAT may be compromised by concurrent treatment with a proton-pump inhibitor (PPI), and the patient should be off such drugs for at least a week before testing. Serology is unaffected by PPI treatment and may be a good option for patients with upper GI bleeding, particularly because the pretest probability of infection is high in this group.
The Guideline recommends two primary regimens for H. pylori infection: clarithromycin-based triple therapy (a PPI, clarithromycin, and amoxicillin or metronidazole) for 14 days and bismuth quadruple therapy (a PPI or H2-receptor agonist, bismuth, metronidazole, and tetracycline) for 10-14 days. The regimens have comparable success in eradicating H. pylori (75%-80%).
Primary-care practitioners tend to focus inordinately on clarithromycin triple therapy, Dr. Chey indicates. “[They] need to realize that quadruple therapy is on an equal footing” and that the rising incidence of clarithromycin resistance makes quadruple therapy an attractive option in many cases. “Always ask whether the patient has received any macrolide antibiotic within the past five years. If so, he or she is much more likely to have a clarithromycin-resistant strain of H. pylori.”
To optimize efficacy of clarithromycin triple therapy, the authors say, a full 14-day course is essential; they also note that twice-daily dosing of the PPI appears to be more effective than once-daily dosing.
Among the drawbacks of bismuth quadruple therapy are the complexity of the regimen and frequency of adverse effects. The latter consideration may be less important than it appears: While minor side effects are indeed common, moderate-to-severe difficulties are no more frequent than with triple therapy.
In light of declining efficacy of both standard regimens, alternative treatments have received increasing attention. The Guideline mentions “sequential” therapy as one such possibility: five days of a PPI and amoxicillin, followed by five days of the PPI, clarithromycin, and tinidazole. This regimen was more efficacious than clarithromycin-based triple therapy in some studies abroad, but it hasn't been validated in North America and cannot be recommended as first-line therapy, the authors say.
While universal testing to prove eradication of H. pylori after antibiotic treatment is not cost-effective, the current Guideline recommends such testing in circumstances broader than those listed in the earlier document. Candidates now include individuals whose dyspeptic symptoms persist despite testing and treatment, along with patients who have an H. pylori-associated ulcer or MALT lymphoma and those who have undergone resection of early gastric cancer.
Retesting should be deferred until four weeks after treatment completion; among nonendoscopic tests, UBT is preferred. Persistent infection indicates the need for retreatment with a different antibiotic regimen.
The American College of Gastroenterology Guideline on the Management of Helicobacter pylori Infection was published in the American Journal of Gastroenterology (2007;102:1808-1825).