Helicobacter Pylori Infection Workup

Updated: Jul 21, 2021
  • Author: Luigi Santacroce, MD; Chief Editor: BS Anand, MD  more...
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Approach Considerations

H pylori gastritis should be categorized on the basis of gastric subsites not only because the risks of gastric cancer and peptic ulcer are affected by gastritis patterns but also because such characterization is key in identifying those who remain at high risk following eradication of H pylori (as defined by the extent and severity of the atrophy) and should thereby undergo regular endoscopic and histologic follow-up. [1]

In addition to recommendations that H pylori gastritis be categorized by gastric subsites, it is also advised that H pylori gastritis should be categorized on the basis of histology (extent/severity of inflammation/atrophy) owing to the risk of development of gastric cancer. [1] Moreover, gastric erosions should not only be reported separately from gastritis but the etiology, natural history, and clinical significance of gastroduodenal erosions should also be evaluated.


Laboratory Studies

Noninvasive diagnostic studies include the carbon 13 urea breath test (UBT), fecal antigen test, and serologic parameters (pepsinogen I and II, H pylori antibody) as surrogate markers of H pylori gastritis and as indicators of gastritis severity. [1, 9]

Patients with new peptic ulcer disease should have a carbon 13 UBT, they should be tested for antibody titers, or they may require an investigation for stool antigens.

H pylori fecal antigen test

This novel rapid test is based on monoclonal antibody immunochromatography of stool samples. The test has been reported to be very specific (98%) and sensitive (94%). The results are positive in the initial stages of infection and can be used to detect eradication after treatment.

Although the H pylori fecal antigen test is an interesting tool, information about the cost of the test is pending.

Carbon 13 urea breath test

The carbon 13 UBT is based on the detection of the products created when urea is split by the organism.

Patients are asked to drink urea (usually with a beverage) labeled with a carbon isotope (carbon 13 or carbon 14). After a certain duration, the concentration of the labeled carbon is measured in the breath. The concentration is high only when urease is present in the stomach. Because the human stomach does not produce urease, such a reaction is possible only with H pylori infection.

The breath test is expensive but is becoming increasingly more available. Other problems include false-negative results due to infection with coccoid forms of H pylori that do not produce as much urease or the use of antibiotics, bismuth, histamine 2 (H2) blockers, or proton pump inhibitors.

H pylori serology

The serology test has a high (>90%) specificity and sensitivity. It is currently based on the quantitation of immunoglobulin G antibodies against H pylori by the means of an enzyme-linked immunosorbent assay.

It is useful for detecting a newly infected patient, but it is not a good test for follow-up of treated patients because the results do not indicate present infection with H pylori. The antibody titer may remain elevated for a long time after H pylori eradication. The number of false-positive results is age related and increases with age.


In geographic areas with a high resistance rate against metronidazole and clarithromycin, culture for antibiotic susceptibility testing (antibiogram) seems to be useful. [3, 4] Alternatively, metronidazole and clarithromycin should not be recommended as first-line drugs in such areas.


Other Tests

Imaging studies are generally not helpful in the diagnosis of H pylori infection. Otherwise, they may be useful in patients with complicated disease (eg, ulcer disease, gastric cancer, MALToma). Advanced endoscopy with clinicians properly trained in image-enhanced modalities (eg, chromoendoscopy, high-resolution magnification endoscopy) and magnification provides a high degree of diagnostic accuracy for gastritis, even before histologic confirmation, as well as for atrophic mucosa and intestinal metaplasia. [1]


In patients with prior peptic ulcer disease, an esophagogastroduodenoscopy (EGD) with biopsy and histological studies may be performed. Also, a carbon 13 urea breath test (UBT) is helpful in these patients.

An EGD is often necessary in patients with symptoms of peptic ulcer disease in order to view the condition of the mucosal lining of the stomach and duodenum and to obtain biopsy specimens from the gastric antrum and corpus.

An echography associated with an EGD is mandatory in patients with biopsy results that are positive for gastric MALTomas in order to allow a more precise staging of the disease.

Histologic examination

Biopsy sampling of both the antrum and corpus is required for histologic accuracy in the evaluation of gastritis. [1]

Peptic ulcer disease and gastric cancer may manifest with the same symptoms, and the only way to differentiate them is to view the lesion and to perform a histologic examination of the biopsy specimens.


Histologic Findings

H pylori is a gram-negative bacterium. It produces urease, has a spiral-like conformation, and is microaerophilic and motile because of the flagella. Flagella and urease are very important for its colonization of the gastric mucosa. Urease neutralizes gastric acidity, converting the gastric urea to ammonium ions, and flagella help the bacterium pass from the acidic gastric lumen into the mucus lining of the stomach. Two of the most important genes of H pylori are VACA and CAGA. The VACA gene codes the Vac-A cytotoxin, a vacuolating toxin, and the CAGA gene codes for Cag-A protein, which seems to stimulate the production of chemotactic factors for the neutrophils by the gastric epithelium of the host.

Biopsy specimens from esophagogastroduodenoscopy (EGD), stained with Giemsa stain, usually demonstrate a variable number of H pylori organisms adhering to the gastric epithelium, both coating the gastric wall and lining the gastric glands. The mucous film appears to be decreased. A large inflammatory infiltrate is present, with lymphocytes, neutrophils, and a variable number of mast cells that seem to play an important role in the pathogenesis of the gastric injury in persons infected with H pylori. [14, 15] Other stains are Genta, Warthin-Starry silver, and the classic hematoxylin and eosin. A rapid urease test may demonstrate the presence of H pylori in the gastric mucosa obtained by endoscopic mucosal biopsy. Bacterial culture is very difficult. It is not used for diagnosis; it is used in patients with resistant infection and for experimental and research purposes.



Although a staging system for the H pylori infection does not exist, some steps in the disease process are well described. The first step is chronic gastritis, followed after a time by the second step, atrophic gastritis. The third step is intestinal metaplasia, which may evolve into dysplasia. The last step is gastric adenocarcinoma. This process is very slow and may stop at any step because gastric cancers undoubtedly require several other factors to develop, not only an H pylori infection. As reported above, ultrasonography and esophagogastroduodenoscopy should be considered in patients with gastric MALTomas in order to allow a more precise staging of the disease.

The risk of gastric cancer is correlated with the severity and extent of atrophic gastritis; histologic staging systems can aid in risk stratification (eg, the operative link for gastritis assessment [OLGA] and operative link for gastric intestinal metaplasia assessment [OLGIM] staging systems). [1]