LAB.00034 Serological Antibody Testing For Helicobacter Pylori

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.

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

H. pylori is a causative agent for peptic ulcers, gastritis, dyspepsia, stomach cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Innovations in the detection of this bacteria have been instrumental in the identification and treatment of pathological H. pylori infections.

Many types of tests have been developed to identify the presence of H. pylori, including urea breath testing (UBT), stool antigen testing, tissue biopsy, and serological testing.

Evidence addressing the use of serological antibody testing is limited to a small number of studies. However, several authoritative 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 has been shown to be inappropriate for follow-up of treated individuals. due to persisting presence 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 is reliant 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 the 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 subjects 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 et al. (2013) evaluated 29 different serological tests on 108 French subjects 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 subjects. 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 American College of Gastroenterology’s clinical guideline for the treatment of H. pylori, the authors only briefly mention antibody testing (Chey, 2017). They note that individuals with peptic ulcer disease have a higher pre-test probability of infection and that testing with an IgG H. pylori antibody test is reasonable. However, in populations with low pre-test probability, tests which identify active infection are preferred.

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 made on the basis of the 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 subjects aged 1 to 18 years who had a first-time esophagogastroduodenoscopy (EGD) between January 2009 and December 2013. Inclusion criteria consisted of subjects who had H. pylori serum antibodies or a fecal antigen test and who had a second EGD with biopsy. The authors found 395 (83%) subjects met the inclusion criteria. There were 79 subjects who were excluded due to prior known history of 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 subjects, 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 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 the use of 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 the swallowing of a slightly radioactive urea tablet which is digested in the stomach by H. pylori into ammonia and carbon dioxide. The amount of radioactive carbon dioxide is measured before and after, and is used to determine the presence or absence of the bacteria.

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When services are Investigational and Not Medically Necessary:
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Subject: Serological Antibody Testing For Helicobacter Pylori
Document #: LAB.00034	Publish Date: 01/03/2024
Status: Reviewed	Last Review Date: 11/09/2023

CPT
86677	Antibody; Helicobacter pylori

ICD-10 Diagnosis
	All diagnoses

Status	Date	Action
Reviewed	11/09/2023	Medical Policy & Technology Assessment Committee (MPTAC) review. Updated Websites section.
Review	11/10/2022	MPTAC review. Updated Rationale and Websites sections.
Review	11/11/2021	MPTAC review. Updated Websites section.
Review	11/05/2020	MPTAC review. Updated Websites section.
Reviewed	11/07/2019	MPTAC review. Updated Rationale, Websites, and Index sections.
Reviewed	01/24/2019	MPTAC review. Updated Description, Rationale, References, and Websites sections.
Reviewed	01/25/2018	MPTAC review. The document header wording updated from “Current Effective Date” to “Publish Date.” Updated Rationale, References, and Websites sections.
New	02/02/2017	MPTAC review. Initial document development.