Medical Policy

This document addresses the use of serological antibody testing for Helicobacter pylori (also known as H. pylori), a causative agent for peptic ulcers, gastritis, dyspepsia and stomach cancer.

Investigational and Not Medically Necessary:

The use of serological antibody testing for Helicobacter pylori is considered investigational and not medically necessary for all indications.

Summary

Detection of H. pylori infection is important because it is linked to peptic ulcers, gastritis, dyspepsia, stomach cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Several diagnostic tools exist, including urea breath tests, stool antigen tests, histopathology, and serological antibody tests. Serological antibody testing has limitations due to persistence of antibodies after eradication, low predictive value in low-prevalence areas, and the need for local validation because of geographic strain variation. While some studies suggest antibody tests may be useful in detecting initial infections, authoritative guidelines caution against their use for monitoring treatment or as a standalone diagnostic tool.

Evidence highlights inconsistent sensitivity and specificity of serological antibody tests, with results varying widely across different populations and methodologies. Meta-analyses and comparative studies generally show that other methods, such as histopathology and stool antigen testing, provide more reliable results. Although some research suggests potential utility in certain clinical contexts, overall accuracy and reproducibility remain concerning. International guidelines, including those from the American College of Gastroenterology (ACG) and the Maastricht Consensus, recommend serological testing only if locally validated, and they discourage its use in confirming eradication. Current evidence does not support serological antibody testing, with stronger, high-quality studies needed before it can be broadly recommended.

Discussion

Evidence addressing the use of serological antibody testing is limited to a small number of studies. However, several organizations have published recommendations on the use of such tests and have identified issues that limit the tests’ clinical utility.

Serological antibody testing is based on the quantitation of immunoglobulin G antibodies against H. pylori. This type of testing may be useful for detecting newly infected individuals but is not appropriate for follow-up of treated individuals due to persistence of antibodies in the bloodstream following H. pylori eradication. Additionally, because there is significant geographical variation in H. pylori strains, testing must be sensitive to the locally prevalent strains. This requires local validation studies of the specific test being used, which may not have been conducted. Finally, because the predictive value of a test relies on the prevalence of a disease. In low prevalence areas such as the U.S., the predictive value of serological antibody testing is low.

In a meta-analysis, Loy and colleagues (1996) compared the results of 21 different studies. The authors observed that the quality of study methodology was often poor for the studies included in their review. Only three of the studies were properly blinded, reference standards varied significantly, and in several studies consecutive participants were not enrolled. The authors noted that their results found that the testing kits being evaluated had a sensitivity of 85% and specificity was estimated to be 79%. Test accuracy was significantly higher in studies with smaller proportions of infected individuals. The meta-analysis concluded that the accuracy of these kits may not be adequate for clinical decision making in all groups. Burucoa (2013) evaluated 29 different serological tests on 108 French participants and found test accuracy to be much lower than reported by Loy. Their findings reported that sensitivity ranged from 55.6% to 100%, specificity from 57.4% to 97.9%, and median accuracy from 73.9% to 97.8%. The positive predictive value ranged from 84.9% to 100% and negative predictive value ranged from 78% to 100%.

Pourakbari and others (2013) reported the results of the only available prospective comparative study addressing the use of H. pylori testing. This study compared the suitability for detection of H. pylori of rapid urease test (RUT), serology, histopathology, and stool antigen tests with polymerase chain reaction (PCR), and correlated these tests with PCR in 89 participants. Histopathology showed high overall performance in adults and children with sensitivity and specificity 100% and 90%, respectively. Sensitivity, specificity, and accuracy for stool antigen test were 87.8%, 75% and 82%, respectively. For serology using IgG, results were 50%, 83.3%, and 65%. Correlation to PCR of RUT, serology, histopathology, and stool antigen testing was 1.0, 0.17, 0.92, and 0.46, respectively.

In the ACG’s clinical guideline for the treatment of H. pylori, the authors only briefly mention antibody testing (Chey, 2024). They note that antibodies may persist in the bloodstream for months to years following successful eradication of H. pylori. This makes serological testing inappropriate for determining post-treatment status..

The Maastricht V/Florence Consensus Report (Malfertheiner, 2016) stated that serological tests may have high accuracy when locally validated. However, the Consensus stated: “Serological tests can only be used after validation.” This recommendation was based on significant geographical variation in circulating H. pylori strains. They reported that the availability of locally validated serological testing for H. pylori was limited and unreliable. This document reiterated the limitations of serological tests in the presence of past infections due to persistence of antigens in the blood stream, and recommended against the use of this serologic testing to monitor the efficacy of eradication.

Raj and colleagues (2017) performed a retrospective study on the H. pylori serum antibody test as a diagnostic screening tool in symptomatic inner-city children. This study design was a chart review of 474 pediatric participants aged 1 to 18 years who had a first-time esophagogastroduodenoscopy (EGD) between January 2009 and December 2013. The study included participants who had H. pylori serum antibodies or a fecal antigen test and who had a second EGD with biopsy. The authors found 395 (83%) participants who met the inclusion criteria. There were 79 participants who were excluded due to prior known H. pylori infection, administration of antibiotics between testing, time between testing, or age. Compared to histology, the serum H. pylori antibody test had a sensitivity of 88.4% and a specificity of 93.4%. The tissue rapid urease test and fecal antigen test had sensitivities of 89.3% and 55.6% and specificities of 89.9% and 98.9%, respectively. The authors suggest that H. pylori antibody testing may be useful as a screening tool in diagnosing symptomatic participants, but acknowledge there were limitations to their study. These limitations included its retrospective design and use of multiple pathologists who were not blinded, which could have caused observer or misclassification bias.

In a Cochrane review, Best and colleagues (2018) evaluated the accuracy of non-invasive tests used alone or in combination in the diagnosis of H. pylori. The results of the literature search yielded 101 studies with 11,003 individuals, of which 5839 individuals (53.1%) were diagnosed with H. pylori. Of the 101 studies, 34 studies (4242 individuals) assessed serological testing. For serological testing, the diagnostic odds ratio was 47.4 (95% confidence interval [CI], 25.5 to 88.1), and the sensitivity (95% CI) estimated at a fixed specificity of 0.90 was 0.84 (95% CI, 0.74 to 0.91). Direct comparison of urea breath test versus serological testing showed a diagnostic odds ratio of 0.68 (95% CI, 0.12 to 3.70; p=0.56). There was limited data for direct comparison of stool antigen test versus serological test. In regard to serological testing, the authors concluded that the results showed low diagnostic accuracy and that higher quality studies are needed to demonstrate clinical utility.

Overall, the evidence regarding the use of serological antibody testing for H. pylori is weak. There are significant concerns regarding accuracy and the ability to identify post-treatment infection. Until additional high-quality data is made available, the use of this type of testing should be considered investigational.

H. pylori is a gram-negative, microaerophilic bacterium found usually in the stomach. It was identified in 1982 by Australian scientists Barry Marshall and Robin Warren, who found that it was present in a person with chronic gastritis and gastric ulcers, conditions not previously believed to have a microbial cause. It is also linked to the development of duodenal ulcers and stomach cancer. However, over 80% of individuals infected with the bacterium are asymptomatic, and it may play an important role in the natural stomach ecology.

More than 50% of the world's population harbor H. pylori in their upper gastrointestinal tract. Infection is more prevalent in developing countries, although incidence is decreasing in Western countries.

The current methods for H. pylori testing include biopsy, stool antigen testing, urea breath test, and H. pylori antibody testing.

Biopsy is an invasive test that requires obtaining a tissue sample from the stomach or other digestive tract organ to confirm the presence of H. pylori. Serum antigen testing uses a blood sample to identify the presence of antibodies to H. pylori. Stool antigen testing is a non-invasive method and identifies antibodies to H. pylori in fecal matter samples. The urea breath test involves swallowing a urea tablet that contains a very small amount of radioactive material. In the stomach, H. pylori (if present) breaks it down into ammonia and carbon dioxide. The tiny amount of radioactive carbon dioxide is then measured before and after. The radiation exposure from this test is minimal and considered safe, and the results help determine whether the bacteria are present.

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When services are Investigational and Not Medically Necessary:
When the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Peer Reviewed Publications:

1. Burucoa C, Delchier JC, Courillon-Mallet A, et al. Comparative evaluation of 29 commercial Helicobacter pylori serological kits. Helicobacter. 2013; 18(3):169-179.
2. Loy CT, Irwig LM, Katelaris PH, Talley NJ. Do commercial serological kits for Helicobacter pylori infection differ in accuracy? A meta-analysis. Am J Gastroenterol. 1996; 91(6):1138-1144.
3. Pourakbari B, Ghazi M, Mahmoudi S, et al. Diagnosis of Helicobacter pylori infection by invasive and noninvasive tests. Braz J Microbiol. 2013; 44(3):795-798.
4. Raj P, Thompson JF, Pan DH. Helicobacter pylori serology testing is a useful diagnostic screening tool for symptomatic inner city children. Acta Paediatr. 2017; 106(3):470-477.

Government Agency, Medical Society, and Other Authoritative Publications:

1. Best LM, Takwoingi Y, Siddique S, et al. Non-invasive diagnostic tests for Helicobacter pylori infection. Cochrane Database Syst Rev. 2018;(3):CD012080.
2.  Chey WD, Howden CW, Moss SF, et al. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2024; 119(9):1730-1753.
3. Malfertheiner P, Megraud F, O'Morain CA, et al.; European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut. 2017; 66(1):6-30.

1. Medline Plus. Tests for H. pylori. Reviewed August 7, 2023. Available at: https://medlineplus.gov/ency/article/007501.htm. Accessed on September 9, 2025.

H. pylori
Heliocbacter pylori

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