LabMed

Helicobacter Pylori

At a Glance

Patients with uninvestigated dyspepsia with active peptic ulcer or with a clinical history of peptic ulcer, and patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma or early gastric cancer might be Helicobacter pylori(H. plyori) infected.

H. pyloriis a gram-negative bacterium that colonizes the luminal surface of the gastric epithelium, representing the most prevalent chronic infection in humans. Generally, H. pylori is not spontaneously cleared from the infected stomach. In the majority of cases, the infection persists asymptomatically during the entire lifespan of the patient, causing only a mild degree gastritis. In a subset of patients (15% of cases), the infection leads, over the years, to the onset of severe upper gastrointestinal disease (i.e., peptic ulcer, MALT lymphoma and gastric cancer). Eradication of the infection is the best approach for the prevention and cure of non-NSAIDs-related peptic ulcer and for the regression of localized MALT lymphomas.

Routine screening test for H. pylori is not proper, since a vast majority of infected patients do not experience any clinical symptoms.

Testing is appropriate in patients with uninvestigated dyspepsia with active peptic ulcer or with a clinical history of peptic ulcer not treated to eradicate the infection, and in patients with gastric MALT lymphoma or subjected to resection for early gastric cancer.

In addition, The Maastricht III but not the American College of Gastroenterology (ACG), guidelines recommend testing in patients with atrophic gastritis, unexplained iron deficiency anemia, and idiopathic thrombocytopenic purpura, as well as in first degree relatives of patients with gastric cancer.

Testing is also appropriate to confirm eradication efficacy in subjects with clinical history of H. pylori-associated peptic ulcer or MALT lymphoma or patients who have undergone resection of early gastric cancer, as well as in patients whose dyspeptic symptoms persist after eradication treatment.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Several tests are available, and the choice of the most appropriate test or the selection of the most accurate combination of tests depends on the tests' performances, local laboratory facilities, patient age, clinical presentation, and presence or absence of alarm symptoms (i.e., gastrointestinal bleeding, anemia, recurrent vomiting, unexplained weight loss, progressive dysphagia, previous gastric malignancy, and family history of gastrointestinal cancer).

Patients 55 years of age or older (ACG guidelines) or 45 years of age or older (Maastricht guidelines) with new onset dyspepsia, or patients with alarm symptoms, are candidates to endoscopy. On gastric mucosal biopsy samples, the Rapid Urease Test (RUT), histology, culture, and Polymerase Chain Reaction (PCR) are available tests for H. pylori detection.

Candidates for noninvasive testing for H. pylori are patients younger than 55 years of age (ACG guidelines) or younger than 45 years of age (Maastricht guidelines) with uninvestigated dyspepsia without alarm symptoms. Three different noninvasive approaches may be adopted alone or in combination: the Serological test for anti H. pylori, the 13C-Urea Breath Test, and the Fecal Antigen Test.

Rapid Urease Test

Gastric biopsies are tested for the presence of the H. pylori-specific urease catalytic activity. This simple, low-cost test identifies active H. pylori infections with excellent specificity and good sensitivity in properly selected patients (not on proton pump inhibitors (PPIs) within 1-2 week or on antibiotic or bismuth within 4 weeks prior to endoscopy). Because of the extensive use of empiric PPIs administration for gastrointestinal (GI) symptoms, the test is often used in combination with other invasive or noninvasive tests for the diagnosis of infection to overcome its decreased sensitivity. Sensitivity is also reduced in post-treatment settings (See Table 1).

Table 1

Laboratory Tests to Diagnose H
13C-Urea Breath Test (first choice) H. pylori stool antigen test (second choice) Anti-H. pylori IgG antibodies in serum (third choice)
Highly sensitive and specific Satisfactorily sensitive and specific; useful when patients are low compliant for 13C-UBT (e.g., infants or very young children) Some limits in sensitivity and specificity; useful in case of bleeding ulcers or chronic atrophic gastritis

Histology

The histological detection of H. pylori in stained sections achieves excellent sensitivity and specificity in advanced infrastructures with well-trained personnel. Sensitivity is affected by PPIs, antibiotics, bismuth medication for the RUT, and by sampling protocols at endoscopy

Culture

The culture of the bacterium in selective media identifies active infections with excellent specificity but less sensitivity than histology or RUT. It is the only standardized method allowing the analysis of antibiotic sensitivities of the infecting strain. Maastricht guidelines recommend H. pylori culture and clarithromycin resistance evaluation before clarithromycin-based treatment in geographical areas where primary resistance to the antibiotic is greater than 15-20%.

Polymerase Chain Reaction

This test detects target sequences of H. pylori DNA by molecular biology amplification methods. PCR testing, although not widely available nor fully standardized, might provide a way to evaluate antibiotic sensitivities and the virulence (genotyping) of the infecting strain.

Anti-H. pylori IgG antibodies

This test relies on the detection of the immunological response of the host to the infection. The test is well standardized, inexpensive, and clinically useful (good positive predictive value, PPV) in populations with high prevalence of the infection. Limits of specificity are present because of false-negative results in early phase of infection (i.e., first 3 weeks) and because of false-positive results (significantly elevated anti-H. pylori IgG titer in the absence of an active infection) owing to the immunological memory. The sensitivity of this test is good but lower than that guaranteed by 13C-Urea Breath Test and the Fecal Antigen Test. Therefore, the serological test should be considered when other tests are possibly false negative (i.e., atrophic gastritis and bleeding ulcers).

13C-Urea Breath Test (13C-UBT)

This test detects the presence of the H. pylori-specific urease catalytic activity in the stomach. Patients are administered per os urea labeled with the stable 13C isotope, which, in the presence of an active H. pylori infection, results in the production of labeled 13CO2 measurable in the expired breath. This test presents excellent sensitivity and specificity in detecting active infections and performs equally well in the evaluation of the efficacy of the eradication treatments.

Stool Antigen Test

This test detects H. pylori-specific antigens in stool samples by means of immunometric assays using monoclonal or polyclonal antibodies. Test sensitivity and specificity are excellent in detecting active infections, although they are slightly lower than those of 13C-Urea Breath Test. Specificity may be reduced in patients with bleeding peptic ulcer. In post-treatment patients, quite excellent test performances are achievable, warranting its use in the evaluation of eradication efficacy.

Follow-up Tests

Follow-up tests are used to monitor the efficacy of the treatment for H. pylori eradication. If follow-up endoscopy is clinically indicated, testing for confirmation of H. pylori eradication is preferably performed by histology alone or in combination with RUT, since the sensitivity of RUT is reduced in post-treatment settings. When endoscopic follow-up is not necessary, the 13C-Urea Breath Test is the first choice, as the Fecal Antigen Test is a good alternative with test protocols implementing monoclonal antibodies. Anti-H. pylori IgG test is not proper to evaluate the efficacy of the eradication therapy because of the potential prolonged immunological memory of an eradicated infection. Culture and antimicrobial sensitivity evaluation are recommended by Maastricht guidelines after two treatment failures with different antibiotics.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

Any drug that causes a decrease in H. pylori colonization density or its urease activity might interfere with lab results. For this reason, PPIs or H2-Receptor Antagonists (H2RAs) have to be stopped 1-2 weeks prior to test sampling, whereas antibiotic and bismuth use have to be stopped at least 4 weeks prior to test sampling.

Therefore, when the aim of testing is to evaluate efficacy of the eradication therapy, sampling should be scheduled 4-8 weeks after its completion.

Reduced specificity of the Fecal Antigen Test and, to a lesser extent, a reduced sensitivity of RUT and histology may be expected in patients with bleeding peptic ulcer.

The use of diagnostic assays employing monoclonal, rather than polyclonal anti-H. pylori antibodies are recommended, in particular, for follow-up evaluation.

What Lab Results are Absolutely Confirmatory?

Culture, histology and 13C-UBT, alone or in combination, are considered the gold standard for H. pylori diagnosis.

Additional Issues of Clinical Importance

In a small subset of subjects (about 2%), the infection may cause gastric cancer, depending on the interaction between bacterial virulence factors and host genetics. The main virulence determinants of H. pylori are the cagA and vacA genes.

It is still unclear whether H. pylori eradication worsens or improves gastroesophageal reflux disease (GERD) symptoms; therefore, the decision to treat or not treat patients for H. pylori infection should not be based on concerns of GERD outcome.

Errors in Test Selection and Interpretation

A serology test cannot be regarded as appropriate to evaluate eradication therapy success if not evaluated as the difference (delta) between pre- and post-therapy titers.

A possible error in the interpretation of results is to consider a positive result of serologic anti-H. Pylori IgG test as an unambiguous sign of active infection.

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