Latest Review Date: May 2024

Category: Medicine/Laboratory                                             

POLICY:

Urea breath testing using the carbon isotope (13C or 14C) or fecal antigen testing for Helicobacter pylori (H. pylori) may be considered medically necessary in patients who meet one of the following criteria below:

• Evaluation of new onset dyspepsia in persons younger than 60 years of age without alarm symptoms (anemia, weight loss, vomiting, lymphadenopathy); OR
• Evaluation of persons with persistent symptoms of dyspepsia despite 2 weeks of appropriate medication therapy for H. pylori; OR
• Evaluation of persons with a prior history of untreated H. pylori infection and with recurrent symptoms.
• Before starting proton pump inhibitor therapy for dyspepsia; OR
• Before bariatric surgery for obesity; OR
• Re-evaluation to assess success of eradication of H. pylori infection (Note: testing to ensure eradication should occur no sooner than 4 weeks post treatment).

Serologic testing for H. pylori may be considered medically necessary in patients who meet one of the following criteria below:

• Evaluation of new onset dyspepsia in patients younger than 60 years of age without alarm symptoms (anemia, weight loss, vomiting, lymphadenopathy); OR
• Before bariatric surgery for obesity

Urea breath testing using the carbon isotope (13C or 14C), fecal antigen testing, or serological testing for Helicobacter pylori (H. pylori) is considered investigational for all other indications, including but not limited to, the following:

• Assessing the risk of developing dementia
• Dyspepsia associated with alarm markers (Endoscopy is recommended)
• Evaluating infantile colic
• Managing recurrent aphthous stomatitis
• New onset dyspepsia in persons aged 60 years or older (upper GI endoscopy is indicated because of concern for gastric neoplasia)
• Screening of asymptomatic person for H. pylori infection

Any combination of simultaneous urea breath testing, fecal antigen testing, and/or serological testing for H. pylori is considered not medically necessary.

DESCRIPTION OF PROCEDURE OR SERVICE:

The recognition of the role of the bacterium Helicobacter pylori (H. pylori) in the pathogenesis of peptic ulcer disease has revolutionized the therapy of peptic ulcer. Specifically, 80% to 95% of patients with duodenal ulcers and 70% to 90% of patients with gastric ulcers have coexisting H. pylori gastritis. Eradication of H. pylori infection using a variety of combinations of antibiotics, bismuth compounds, and acid suppression therapy has emerged as a basic treatment strategy for these ulcers. However, it is important to realize that the majority of patients positive for H. Pylori do not develop ulcer symptoms.  In addition, the role of H. Pylori therapy in non-ulcer dyspepsia alone is uncertain. Dyspepsia refers to a group of symptoms which include epigastric pain or discomfort, indigestion, upset stomach, bloating or nausea. Some dyspepsia symptoms (e.g. postprandial gnawing or burning relieved by foods or antacids) are suggestive of ulcers. Other symptoms (e.g. belching, bloating, or fullness) may be related to non-ulcer dyspepsia.  Nevertheless, there is considerable overlap between ulcer and non-ulcer dyspepsia.  Invasive detection of H. Pylori involves upper GI endoscopy with a biopsy. Non-invasive methods include serologic identification of anti-H. Pylori antibodies, detection of H. Pylori antigens in the feces, or the urea breath test (UBT). While serologic tests indicate either past or present infection, fecal antigens and UBT indicates active disease.

Noninvasive Testing for H. pylori

Urea Breath Test (UBT)

Urea breath testing is based on the high urease activity of H. pylori, which hydrolyzes urea to carbon dioxide and ammonia. In the urea breath test, the patient ingests urea labeled with a carbon isotope, either 13C or 14C, and then the concentration of the isotope is measured in the expired CO2. Analysis of the concentration of 13C requires the use of mass spectrometry, and the sample must be submitted to the manufacturer’s reference laboratory for analysis. In contrast, 14C is radioactive, and while its use exposes the patient to a small dose of radiation, its presence can be measured using scintillation counting.

Fecal Antigen Test

H. pylori antigens can be detected in the stool by applying antibodies to a diluted stool sample complexed to a detection molecule.

Serological Test

Serological testing for H. pylori does not dependably differentiate between active and past infections, and additionally, it requires validation at the local level. The sensitivity and specificity of serological testing has been reported to be 85% and 79% respectively.

KEY POINTS:

A literature search was performed through May 2, 2024.

Summary of Evidence

For individuals undergoing testing for H. pylori for new onset dyspepsia evaluation in those age 60 and under with no alarm symptoms, evaluation of persistent symptoms of dyspepsia despite 2 weeks of medication therapy, evaluation of those with a history of untreated H pylori with recurrent symptoms, prior to starting PPI therapy, prior to bariatric surgery, or re-evaluation to assess H. pylori status, the evidence consists of meta-analyses and prospective studies.

The sensitivity and specificity of the UBT is reported to be 88% and 95-100%, respectively. False positive results are uncommon.  The sensitivity and specificity of the fecal antigen test is reported to be 94% and 97%, respectively. This testing can be affected by PPIs, bismuth, and/or antibiotics as well and should be discontinued prior to testing.  The evidence is sufficient to determine the effects of the technology on health outcomes.

For individuals undergoing testing for H. pylori for the risk of developing dementia, dyspepsia with alarm markers, evaluating infantile colic, managing recurrent aphthous stomatitis, new onset dyspepsia older than 60 years, and the screening of asymptomatic patients for HP infection, the evidence consists of cohort studies and case control studies. Overall, the evidence is weak and only hypotheses are presented in several of the studies. High quality and long-term data are needed to determine the net health outcome. The evidence is insufficient to determine the effects of the technology on health outcomes.

Practice Guidelines and Position Statements

American College of Gastroenterology (ACG)

In 2017, the ACG and the Canadian Association of Gastroenterology published a joint guideline on the management of dyspepsia.

The summary and strength of recommendations are in Table 1.

Table 1: Management of dyspepsia

FD, functional dyspepsia; H. pylori , Helicobacter pylori ; PPI, proton pump

inhibitor; TCA, tricyclic antidepressant.

Also in 2017, the ACG updated their clinical guidelines regarding the treatment of Helicobacter pylori. 

The indications to test for, and to treat, H. pylori infection are in Table 2.

Table 2: Indications to test for and treat H. pylori

KEY WORDS:

Helicobacter pylori (H. pylori), urea breath test (UBT), 13C isotope, 14C isotope, dyspepsia, peptic ulcer disease, fecal antigen test, serological testing

APPROVED BY GOVERNING BODIES:

The FDA has approved multiple tests for urea breath testing and fecal antigen testing.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits.  Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP: Special benefit consideration may apply. Refer to member’s benefit plan. 

CURRENT CODING: 

CPT Codes:

REFERENCES:

1. Ali AM. Helicobacter pylori and infantile colic. Arch Pediatr Adolesc Med. 2012 Jul 1; 166(7):648-50.
2. American Gastroenterological Association.  American Gastroenterological Association Medical Position Statement:  Evaluation of Dyspepsia, Gastroenterology, November 2005; 129: 1753-1755.
3. Baudron RC, Letenneur L, Langlais A, et al. Does helicobacter pylori infection increase incidence of dementia? The personnes agees QUID study. J Am Geriatr Soc. 2013 Jan; 61(1):74-8.
4. Chaves LC, Borges IK, Souza MD, et al. Inflammatory disorders associated with helicobacter pylori in the roux-en-y bypass gastric pouch. Arq Bras Cir Dig. 2016; 29Suppl1(Suppl1):31-34.
5. Chey WD, Leontiadis GI, Howden CW, et al. ACG clinical guideline: Treatment of helicobacter pylori infection. Am J Gastroenterol. 2017 Feb; 1112(2):212-239.
6. Czinn SJ.  Helicobacter Pylori infection: Detection, investigation, and management. Journal of Pediatrics, March 2005, Vol. 146, No. 3 Suppl.
7. Fani L, Wolters FJ, Ikram MK, et al. Helicobacter pylori and the risk of dementia: A population based study. Alzheimer’s Dement. 2018 Jun 20. Pii: S1552-5260 (18) 3030159-6.
8. Ferwana M, Abdulmajeed I, Alhajiahmed A, et al. Accuracy of urea breath test in helicobacter pylori infection: meta-analysis. World J Gastroenterol. 2015 Jan 28; 21(4):1305-14.
9. Gomes CC, Gomez RS, Zina LG, Amaral FR. Recurrent aphthous stomatitis and helicobacter pylori. Med Oral Patol Oral Cir buccal. 2016 Mar 1; 21(2):e187-91.
10. Han YH, Zhang W, Wang YT, Xiong ZJ, Du Q, Xie Y, Lu H. Performance evaluation of a novel 14C-urea breath test (solid scintillation) for the diagnosis of helicobacter pylori infection. Medicine (Baltimore). 2023 Mar 3;102(9).
11. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
12. Iqbal S, Fatima S, Raheem A, et al. Agreement between serology and histology for detection of helicobacter pylori infection. J Coll Physicians Surg Park. 2013 Nov; 23(10):784-6.
13. Kaplan LM. Gastrointestinal management of the bariatric surgery patient. Gastroenterology Clinics, March 2005, Vol. 34, No. 1.
14. Li H, Shen Y, Song X, et al. Need for standardization and harmonization of Helicobacter pylori antimicrobial susceptibility testing. Helicobacter 2022; 27:e12873.
15. Ling D. Caron 13 urea breath test for helicobacter pylori infection in patients with uninvestigated ulcer like dyspepsia: an evidence based analysis. Ont Health Technol Assess Ser. 2013 Oct 1; 13(19): 1-30.
16. Mocanu V, Dang JT, Switzer N, et al. The effect of helicobacter pylori on postoperative outcomes in patients undergoing bariatric surgery: a systematic review and meta-analysis. Obes Surg. 2018 Feb; 28(2):567-573.
17. Moayyedi PM, Lacy BE, Andrews CN, et al. ACG and CAG clinical guideline: Management of dyspepsia. Am J Gastroenterol. 2017; 112(7):987.
18. National Institute for Clinical Excellence (NICE). Dyspepsia-management of dyspepsia in adults in primary care. London, UK 2004.
19. National Institutes of Health (NIH) Consensus Statement. Helicobacter Pylori in peptic ulcer disease. January 1994, pp. 1-23.
20. Saha R, Roy P, Das S, et al. Application of a stool antigen test to evaluate the burden of helicobacter pylori infection in dyspepsia patients. Indian J Pathol Microbiol. 2016 Jan-Mar; 59(1):66-8.
21. The Helicobacter Foundation. Epidemiology. www.helico.com/epidemiology.html. 
22. Tsolaki F, Kountouras J, Topouzis F, et al. Helicobacter pylori infection, dementia and primary open angle glaucoma: Are they connected? BMC Ophthalmol. 2015 Mar 11; 15:24.
23. Vaz Coelho LG, Trindade OR, Leao LA, et al. Prospective study for validation of a single protocol for the 13C urea breath test using two different devices in the diagnosis of H. pylori infection. Arq Gastroenterol. 2019 Aug 13;56(2):197-201.

POLICY HISTORY:

Medical Policy Group, October 2005 (3)

Medical Policy Administration Committee, November 2005

Available for comment December 1, 2005-January 14, 2006

Medical Policy Group, January 2006 (3)

Medical Policy Administration Committee, February 2006

Available for comment February 16-April 3, 2006

Key Points updated with ACG guidelines, no policy change, February 2008 (1)

Medical Policy Group, February 2010 (1) Updated Key Points

Medical Policy Administration Committee, February 2010

Medical Policy Group, February 2013: Effective 02/06/2013: Active Policy but no longer scheduled for regular literature reviews and updates.

Medical Policy Group, October 2013 (1): Removed ICD-9 Diagnosis/Procedure codes; no change to policy statement.

Medical Policy Group (4): Updates to Description, Policy, Key Points, Key Words, Approved by Governing Bodies, Current Coding and References. Updated policy section by adding bariatric surgery under UBT/fecal antigen testing, updated age for evaluation of new onset dyspepsia to younger than 60, added additional IV criteria. Added Key Word serological testing. Added CPT code 86677 to Current Coding.

Medical Policy Administration Committee, August 2018.

Available for comment July 27 through September 9, 2018.

Medical Policy Group, May 2021 (4): Updates to Key Points and References.  Policy statement updated to remove “not medically necessary,” no change to policy intent.

Medical Policy Group, May 2022 (5): Minor update to Key Points. Reviewed by consensus. There is no new published peer-reviewed literature available that would alter the coverage statement in this policy.

Medical Policy Group, May 2023 (11) Minor update to Key Points, Benefit Application, and References. Reviewed by consensus. There is no new published peer-reviewed literature available that would alter the coverage statement in this policy.

Medical Policy Group, May 2024 (11) Minor update to Key Points, Benefit Application, and References. Reviewed by consensus. There is no new published peer-reviewed literature available that would alter the coverage statement in this policy.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.