HELICOBACTER PYLORI INFECTION
Helicobacter pylori is a gram-negative bacteria initially cultured from the human stomach in 1982 and considered the most common cause of gastric mucosal injury. It produces large amounts of urease that protects from acid injury, enabling it to penetrate gastric epithelial cells. The transmission mechanism of H. pylori remains unclear. Interpersonal transmission appears to be the main route; transmission by environmental substances, such as contaminated water, is another cause.
The
prevalence of H. pylori is high in the global population (≈50%); it is less
frequent in developed areas such as Northern Europe and North America (≈30%) compared with Asia
and Africa. The worldwide prevalence in the younger generations is declining,
mainly in developed countries.
The bacteria
causes gastritis; if it persists, gastric atrophy with intestinal metaplasia
eventually affects the gastric acid secretion level, based on the location and
severity of the inflammation in the stomach. H. pylori reduces the
mucosal gel layer and affects mucosal blood flow. It is the main cause of
duodenal ulcer, through increase in acid pepsin and gastric metaplasia in the
duodenal cup. In addition to the host factor and diet, virulence factors of H.
pylori (CagA, VacA, DupA, IceA, OipA, and BabA) have been revealed to be
the predictors of gastric atrophy, intestinal metaplasia, duodenal ulcer, and
gastric cancer. However, there is no evidence that strategies based on testing
for these factors are useful for an individual patient.
Although H.
pylori infection does not always cause clinical disease, it strongly
affects the relative risk of various disorders in the upper gastrointestinal
tract, such as gastritis, peptic ulcer disease, gastric cancer, MALT lymphoma,
idiopathic thrombocytopenic purpura, and iron deficiency anemia. On average,
the H. pylori status has no
effect on symptom severity, recurrence, or treatment efficacy in patients with
GERD. Many patients have functional dyspepsia symptoms rather than peptic ulcer
disease.
Endoscopic
biopsies enable culture and histologic examination with excellent results. The
rapid urease test and polymerase chain reaction procedure for gastric biopsy
specimens also have a high yield. The noninvasive C13-urea breath test and
stool antigen test have high sensitivity and specificity, and both tests are
recommended for detection. However, proton pump inhibitors and antibiotic
treatment can affect and inhibit urease activity. Serologic results for anti H. pylori antibodies are not all
equivalent, and only validated immunoglobulin G serology tests should be used
owing to variability in different commercial tests.
H. pylori
infection
is the most consistent risk factor for gastric cancer. Its elimination is the
most promising strategy for reducing the incidence of gastric cancer and
lowering the risk of recurrent peptic ulcer bleeding. Guidelines therefore
advocate a test-and-treat strategy for patients with a history of ulcer
bleeding and NSAID and/or aspirin use.
The
first-line treatment is a proton pump inhibitor combined with clarithromycin
and amoxicillin for 10 to 14 days. Regimens containing clarithromycin are the
first-line treatment only in areas of low clarithromycin resistance (≤20%). Regimens
containing four agents, including bismuth, are alternative first-line
treatments. If this regimen is not available, sequential treatment or a
four-agent regimen not containing bismuth is recommended. If proton pump
inhibitor clarithromycin therapy fails, either
four-agent therapy including bismuth or three-agent therapy containing
levofloxacin is recommended (rising rates of levofloxacin resistance should be
taken into account, however). Choosing a third-line regimen should be guided by
antimicrobial susceptibility testing whenever possible.
Confirmation
of eradication is recommended at least 4 weeks after treatment. A urea breath
test or monoclonal stool test is recommended as a noninvasive test for
determining eradication success; currently, there is no role for serologic
testing. In countries where H. pylori infection is prevalent, studies focusing on virulence
factors and antibiotic susceptibility may improve the prognosis and be helpful in reducing complications
and the risk of death.
H. pylori
posteradication
recurrence is infrequent and is found mainly in areas of low socioeconomic
development. Eradication reduces the risk of complicated and uncomplicated
peptic ulcer disease associated with use of NSAIDs or low-dose acetylsalicylic
acid. H. pylori eradication is beneficial before starting NSAID
treatment, and mandatory in patients with a history of pelvic ulcer disease.
Eradication produces long-term relief of dyspepsia in 1 of 12 patients with
functional dyspepsia, a rate that is better than for any other treatment available.
