Medical Policy



Subject: Serological Antibody Testing For Helicobacter Pylori
Document #: LAB.00034 Current Effective Date:    03/29/2017
Status: New Last Review Date:    02/02/2017

Description/Scope

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

Position Statement

Investigational and Not Medically Necessary:

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

Rationale

H. pylori is a causative agent for peptic ulcers, gastritis, dyspepsia and 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.

At this time, the available evidence addressing the use of serological antibody testing is limited to a small number of older studies. However, several major authoritative organizations have published recommendations on the use of such tests as well as identified issues which limit its 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 the persistent 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, and the overall observation of the authors was that the quality of the study methodology was often poor. 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 measured was significantly higher in studies with smaller proportions of infected individuals. The study concluded that the overall accuracy of these kits may not be adequate for clinical decision making in all groups. The findings by Loy regarding accuracy were contradicted in a more recent study by Burucoa et al. (2013) evaluating 29 different serological tests on 108 French subjects. 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 of rapid urease test (RUT), serology, histopathology, and stool antigen tests with polymerase chain reaction (PCR) for detection of H. pylori, and correlated the diagnostic methods 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.

Talley and others on the American College of Gastroenterology's (ACG) Practice Parameters Committee published guidelines for the management of dyspepsia in 2005. In this document they comment on the use of serological tests, stating that the sensitivity and specificity of the available serological tests was suboptimal. They further note that the positive and negative predictive value of serological testing is dependent upon background prevalence of H. pylori infection. As such, in low-prevalence areas, such as the U.S., a positive test is more likely to be a false positive.

The ACG published another document, its Guideline on the Management of Helicobacter pylori Infection (Chey, 2007), which further discusses the fact that results of antibody tests are highly susceptible to geographic variation in H. pylori antigens, and test results are hence limited to the area in which they were developed. As noted in the 2005 ACG document mentioned above, the prevalence of H. pylori infection has significant impact on predictive value of serological testing. The ACG states that in low prevalence areas such as the U.S, "a positive test is no better than a coin toss in predicting the presence of active infection." Finally, its recommendations state that antibody tests are of little benefit in documenting eradication results as results can remain positive for years following successful cure of the infection, and as such they should be avoided in the post-treatment setting.

In a more recent ACG clinical guideline for the treatment of H. pylori, the authors only briefly mention antibody testing at all (Chey, 2017). They only 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.

Finally, the Maastricht V/Florence Consensus Report (Malfertheiner, 2016) stated 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, as noted above by the ACG. At this time, the availability of locally validated serological testing for H. pylori is limited and unreliable. This document also reiterates the limitations of serological tests in the presence of past infections due to persistence of antigens in the blood stream, and does not recommend the use of this type of test to monitor the efficacy of eradication.

Overall, the evidence regarding the use of serological antibody testing for H. pylori is weak, and raises 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.

Background/Overview

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.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.  

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.

CPT  
86677 Antibody; Helicobacter pylori
   
ICD-10 Diagnosis  
  All diagnoses
   
References

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.

Government Agency, Medical Society, and Other Authoritative Publications: 

  1. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: Treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017; 112(2):212-239.
  2. Chey WD, Wong BC.; Practice Parameters Committee of the American College of Gastroenterology. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007; 102(8):1808-1825.
  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.
  4. Talley NJ, Vakil N.; Practice Parameters Committee of the American College of Gastroenterology. Guidelines for the management of dyspepsia. Am J Gastroenterol. 2005;100(10):2324-2337.
Websites for Additional Information
  1. Medline Plus. Tests for H. pyliori. Reviewed August 14, 2016. Available at: https://medlineplus.gov/ency/article/007501.htm . Accessed on November 11, 2016.
Index

H. pylori

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Document History
Status Date Action
New 02/02/2017 Medical Policy & Technology Assessment Committee (MPTAC) review. Initial document development.