Gastroenterology training and education

What are the tests available for HP infection?

Urea breath test (UBT)

• The diagnostic accuracy of the UBT is more than 95% in studies.
• UBT is based upon the hydrolysis of urea by H. pylori to produce CO2 and ammonia. A labeled carbon isotope is given by mouth; H. pylorus liberates tagged CO2, which can be detected in breath samples.
• Two UBTs are FDA approved: the non-radioactive 13C test and the radioactive 14C test. Both tests can be performed in 15 to 20 minutes and have similar cost and accuracy. 13C is preferred by some as it does not use a radioactive isotope; however the dose of radiation in the 14C test is minimal.
• Test- A baseline breath sample is collected before the patient ingests 13C-urea, i.e., urea labeled with a naturally occurring, non-radioactive carbon isotope. A second sample is collected shortly after the ingestion. H pylori-associated urease degrades the urea, producing ammonia and CO2. The resultant CO2 is absorbed in the blood and then exhaled. An increase in the ratio of 13CO2 to 12CO2 between the pre- and post-ingestion samples indicates the presence of H pylori-associated urease.
• Before conducting the UBT, the patient should be off antibiotics, PPI and bismuth for at least 2 weeks. Patients can remain on H2 blocker therapy.

Stool antigen tests

• Sensitivity and specificity I than 90%.
• The test is based on a sandwich EIA with antigen detection. This is a qualitative test with an animal anti-H.pylori antibody adsorbed to microwells as capture antibody.
• The patient simply collects a stool sample in a clean, dry container.
• PPI, antibiotic and bismuth suppresses H. pylori and thus reduces faecal antigen values, resulting in a decreased accuracy.

Serology

• ELISA technology is used to detect IgG or IgA antibodies
• The diagnostic accuracy is low (80–84%) with high sensitivity (90 to 100 percent), but variable specificity (76 to 96 percent).
• Positive serology indicates current or past infection with H.pylori. A positive test does not confirm active disease.
• A negative serological test provides >95 % assurance that there is no H.pylori infection.
• Serology should not be used in the evaluation of treatment of H.pylori because the antibody titre takes many months (or even years) to decline.

Rapid urease test (RUT test)

• The sensitivity and specificity is more than 90%.
• Obtaining tissue samples from the antrum and the fundus may increase the sensitivity of the test in these patients.
• The CLO test is a qualitative RUT assay based on the detection of urease, produced by H. pylori.
• The test system consists of a test well filled with a urea containing gel where the suspected tissue is inoculated and allowed to incubate. If H. pylori is present in the patient’s sample, urease will hydrolyze the urea in the gel leading to an accumulation of ammonium ions (NH4 +). This causes a rise in pH which is detected by a pH indicator in the test system changing from yellow to magenta. Other shades of red such as pink or orange are also considered positive. Yellow is considered a negative screen.
• Gastric biopsy specimen should be taken preferably from an area that is not as eroded or denuded; H. pylori is present in smaller numbers in these areas than in otherwise normal looking tissue.
• A CLO is reported as negative if there is no change in colour until the end of the 24 hour period.
• CLO test may be falsely negative  in patients with recent gastrointestinal bleeding or with the use of PPIs, H2 antagonists, antibiotics, or bismuth-containing compounds as these agents suppress H. Pylori

Histology
The density of HP may vary at different sites and this may lead to sampling error. There may also be interobserver variability with histology. The sensitivity of histology may be decreased in patients taking anti secretory therapy, but is still higher in this setting than rapid urease testing. The sensitivity and specificity of histology is more than 90%
HP culture

Biopsies for culture should be obtained before the forceps are contaminated with formalin. The tissue should be placed into a container with a few drops of saline. Cultures have 80-90% sensitivity and 100% specificity

Which test to use?

• The American College of Gastroenterology guidelines recommend the UBT as “the best non endoscopic test for documenting H. pylori infection,” although stool antigen testing is equally accurate and is more widely available.
• Rapid urease test is the easiest and cheapest endoscopic test in the absence of GI bleed or current use of PPI or antibiotics
• The accuracy of various methods to detect HP may be affected in the presence of recent bleeding. Sensitivity is low but specificity is high for biopsy-based methods (RUT, histology and culture) in the presence of GI bleed. With respect to noninvasive tests in presence of GI bleed, a metanalyses showed that sensitivity and specificity were 93 and 92 percent for the (13)C urea breath test, 87 and 70 percent for the stool antigen test, and 88 and 69 percent for serology. A biopsy should be done, if possible at the time of endoscopy. If this is negative for HP, UBT should be preferentially used, although stool antigen test and serology are alternatives.
• Serology is also useful as a diagnostic test when others could be false negative, such as in patients with a low bacterial density like gastric atrophy, MALT lymphoma and with recent or current use of PPIs and antibiotics.

Discuss use of helicobacter tests to confirm eradication?

• Urea breath testing performed at least four weeks after treatment has been promoted as the test of choice to confirm eradication of infection.
• Stool antigen testing is a more widely available alternative, but it may be less accurate. Serologic testing is not useful for follow-up since many patients continue to have antibodies for months or even years after eradication therapy
• PPI, Antibiotics and bismuth should be discontinued for at least two weeks prior to testing done to confirm H. pylori cure (with urea breath test, stool antigen testing, or endoscopic testing) to reduce the chance of false-negative results.