Aetna considers carbon isotope (13C or 14C) urea breath testing or stool antigen testing medically necessary in selected persons who meet any of the following criteria:
Evaluation of new onset dyspepsia; or
Evaluation of persons with persistent symptoms of dyspepsia despite 2 weeks of appropriate antibiotic therapy for Helicobacter pylori (H. pylori); or
Recurrent dyspeptic symptoms suggesting re-infection with H. pylori; 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).
This policy is consistent with guidelines of the American Gastroenterological Association (2005) and the American College of Gastroenterology (2007).
Aetna considers urea breath testing and stool antigen testing experimental and investigational for all other indications, including any of the following because their effectiveness for indications other than the ones listed above has not been established:
Assessing risk of developing dementia; or
Dyspepsia associated with “alarm” markers, e.g., anemia, gastrointestinal bleeding, obstruction, perforation, anorexia, early satiety, or weight loss (upper gastrointestinal [GI] endoscopy is indicated); or
Evaluating infantile colic; or
New-onset dyspepsia in persons aged 55 years or older (upper GI endoscopy is indicated because of concern about gastric neoplasia); or
Screening of asymptomatic persons for H. pylori infection.
Aetna considers laboratory-based H. pylori serology medically necessary for evaluating persons with dyspepsia. Aetna considers office-based H. pylori serology experimental and investigational because of its inadequate performance.
Aetna considers simultaneous urea breath testing and stool antigen testing for H. pylori not medically necessary because concurrent testing with both methods is not necessary.
Aetna considers the TZAM H. pylori Multiplex PCR experimental and investigational because of insufficient evidence of its effectiveness.
Aetna considers plasma pepsinogen II testing experimental and investigational for evaluation of the success of H. pylori eradication because of insufficient evidence of its effectiveness.
More than 90 % of gastroduodenal ulcers are associated with Helicobacter pylori (H. pylori, formerly known as Campylobacter pylori) infection, whether on first presentation or on recurrence. Since cure of H. pylori infection facilitates healing and decreases recurrence rates, antibiotic therapy is indicated for all H. pylori -infected ulcer patients. Simultaneous conventional ulcer therapy using acid-suppressing drugs is recommended to facilitate symptom relief and healing.
Confirmation of the presence of the H. pylori bacterium can be determined non-invasively using a urea breath test or a stool antigen test, or invasively on endoscopic biopsy followed by rapid urease testing (CLOtest™, PyloriTek™, Hpfast™), histology with special stains, or culture.
The stool antigen test (Meridian bioscience HpSA) and the urea breath tests (Meretek UBT™, PYtest™) determine the presence of active H. pylori infection. The stool antigen test is cleared by the U.S. Food and Drug Administration (FDA) for use in the initial diagnosis, therapeutic monitoring and eradication confirmation in adults and children. The stool antigen test is based on the passage of H. pylori bacteria and H. pylori antigens in the gastrointestinal tract, and their detection by immunoassay.
Urea breath tests are cleared by the FDA for the initial diagnosis, and eradication confirmation in adults, and are based on the fact that H. pylori bacteria produce a urease that breaks down labeled carbon-13 (13C) or carbon-14 (14C) urea to ammonia and carbon dioxide, which can be detected in an exhaled sample from the lungs.
According to guidelines from the American Gastroenterological Association (2005) and the American College of Gastroenterology (2007), urea breath testing or stool antigen testing are the non-invasive methods of choice for detecting new infection in younger patients without alarm symptoms. Patients older than 55 years of age and younger patients with alarm symptoms (e.g., weight loss, progressive dysphagia, recurrent vomiting, evidence of gastrointestinal bleeding, or family history of upper gastrointestinal cancer) should be evaluated by endoscopy with biopsy (AGA, 2005; ICSI, 2003). The stool antigen test and the urea breath test are also the tests of choice in those situations where post-treatment testing is required. Serology is not useful in this situation as antibody levels commonly remain elevated for months to years after successful treatment.
Stool antigen testing is the preferred method of testing for H. pylori infection in pediatric patients, as it has been cleared by the FDA for use in both adults and children. The urea breath test is cleared by the FDA only for use in adults (18 years of age and older).
The American College of Gastroenterology no longer recommends serology for detection of H. pylori infection. A negative serology for H. pylori antibody can be used to rule out infection. However, a positive serology only determines that a patient has been exposed to H. pylori at some time in the past, but not whether the patient is currently infected. Studies indicate that about 50 % of persons with a positive H. pylori serology do not have active infection (ACG, 2007). Moreover, serology can not be used to show that H. pylori have been successfully eradicated after treatment, as antibody levels commonly remain elevated for months to years after treatment.
Guidance from the National Institute for Health and Care Excellence (NICE, 2014) recommends testing for H pylori using a carbon-13 urea breath test or a stool antigen test, or laboratory-based srology where its performance has been locally validated. The guidelines recommend against using office-based serological tests for H. pylori because of their inadequate performance.The guidelines state that serology has been widely used in clinical practice and two metaanalyses indicate that sensitivity and specificity are usually greater than 85% (citing Loy, et al., 1996 Roberts, et al., 2000). The sensitivity and specificity of serology varies in different populations. The reason for this is uncertain but may relate to different strains of H pylori or genetic differences in the population causing diverse immune responses. The appropriate cut-off for a commercial kit being used should therefore be locally validated. The guidelines state that near patient serology tests have been developed, where the result is obtained in situ rather than from a laboratory, but the accuracy of these kits varies widely in different communities (NICE, 2014).
New guidelines from the American College of Gastroenterology indicate post-treatment testing in all patients treated for H. pylori infection (ACG, 2007). Previously published guidelines recommended post-treatment testing only in individuals with refractory symptoms or those with complicated ulcer disease, including low-grade gastric mucosa associated lymphoid tissue (MALT) lymphoma and resected gastric cancer (ICSI, 2003; Howden and Hunt, 1998).
According to ACG guidelines, all persons suspected of having peptic ulcer disease should be tested for H. pylori regardless of whether they are on non-steroidal anti-inflammatory drugs (NSAIDS). The guidelines note that H. pylori and NSAIDs are independent risk factors for the development of peptic ulcer disease.
Stenstrom et al (2008) stated that urea breath tests are the best way to diagnose current H. pylori infection. Serology should primarily be used when urea breath tests may be false-negative (e.g., current bleeding ulcer or H. pylori suppressing drugs). For children who can not use urea breath tests, stool antigen tests may be useful.
In a case-control study, Ali (2012) examined if H. pylori is associated with infantile colic. A total of 55 patients with infantile colic who were 2 weeks to 4 months of age and who fulfilled modified Wessel criteria (i.e., crying and fussy behavior) and a total of 30 healthy controls with no history of colic who were matched by country of origin, age, sex, and ethnicity to the 55 colicky infants were included in this study. Main outcome measure was H. pylori infection determined by stool antigen testing. Of the 55 patients presenting with infantile colic, 45 (81.8 %) tested positive for H pylori; of the 30 healthy controls, 7 (23.3 %) tested positive for H pylori (odds ratio, 15.3 [95 % confidence interval: 17.9 to 29.8]). The author concluded that H pylori infection is associated with infantile colic and may be a causative factor.
Kheir (2012) stated that infantile colic is defined as paroxysms of crying lasting more than 3 hours a day, occurring more than 3 days in any week for 3 weeks in a healthy baby aged 2 weeks to 4 months. Colic is a poorly understood phenomenon affecting up to 30 % of babies, underlying organic causes of excessive crying account for less than 5 %. Laboratory tests and radiological examinations are unnecessary if the infant is gaining weight normally and has a normal physical examination. Treatment is limited and drug treatment has no role in management. Probiotics are now emerging as promising agents in the treatment of infantile colic. Alternative medicine (herbal tea, fennel, glucose, and massage therapy) have not proved to be consistently helpful and some might even be dangerous. The author concluded that infantile colic is a common cause of maternal distress and family disturbance, the cornerstone of management remains reassurance of parents regarding the benign and self-limiting nature of the illness. There is a critical need for more evidence based treatment protocols.
UpToDate reviews on “Evaluation and management of colic” (Turner and Palamountain, 2012a) and “Clinical features and etiology of colic” (Turner and Palamountain, 2012b) do not mention H. pylori testing in the evaluation of infantile colic.
Roubaud Baudron et al (2013) examined if H. pylori infection was associated with dementia and risk of developing dementia in a longitudinal population-based cohort of elderly adults living in the community. A total of 603 non-institutionalized individuals aged 65 and older living in the southwest of France followed from 1989 to 2008 were included in this study. A descriptive and comparative analysis including dementia prevalence, according to H. pylori status (serology), was made at baseline. Cox proportional hazard models were used to study the risk of developing dementia according to H. pylori status assessed on sera samples from elderly adults initially free of dementia and followed for 20 years. A neurologist diagnosed dementia according to Diagnostic and Statistical Manual of Mental Disorders Third Edition criteria. At baseline, 391 (64.8 %) subjects (348 women, mean age of 73.9 ± 6.5 years) were sero-positive for H. pylori. Dementia prevalence was higher in the infected group (5.4 % versus 1.4 %, p = 0.02). After 20 years of follow-up, 148 incident cases of dementia were diagnosed. After controlling for age, sex, educational level, apolipoprotein E4 status, cardiovascular risk factors, and Mini-Mental State Examination score, H. pylori infection was determined to be a risk factor for developing dementia (hazard ratio = 1.46, p = 0.04). The authors concluded that this longitudinal population-based study provided additional epidemiological support to the hypothesis of an association between dementia and H. pylori infection, which may enhance neurodegeneration. More research is needed to test this hypothesis.
Lopes and colleagues (2014) stated that considering the recommended indications for H. pylori eradication therapy and the broad spectrum of available diagnostic methods, a reliable diagnosis is mandatory both before and after eradication therapy. Only highly accurate tests should be used in clinical practice, and the sensitivity and specificity of an adequate test should exceed 90 %. The choice of tests should take into account clinical circumstances, the likelihood ratio of positive and negative tests, the cost-effectiveness of the testing strategy and the availability of the tests. This review concerned some of the most recent developments in diagnostic methods of H. pylori infection, namely the contribution of novel endoscopic evaluation methodologies for the diagnosis of H. pylori infection, such as magnifying endoscopy techniques and chromoendoscopy. In addition, the diagnostic contribution of histology and the urea breath test was explored recently in specific clinical settings and patient groups. Recent studies recommended enhancing the number of biopsy fragments for the rapid urease test. Bacterial culture from the gastric biopsy is the gold standard technique, and is recommended for antibiotic susceptibility test. Serology is used for initial screening and the stool antigen test is particularly used when the urea breath test is not available, while molecular methods have gained attention mostly for detecting antibiotic resistance.
An UpToDate review on “Indications and diagnostic tests for Helicobacter pylori infection” (Crow, 2014) states that “Polymerase chain reaction (PCR) is not practical for the routine diagnosis of H. pylori. It may, however, be useful in detecting the organism when ordinary culture is difficult, as with testing stool or drinking water”.
Leja et al (2014) noted that pepsinogen levels in plasma are increased by inflammation in the gastric mucosa, including inflammation resulting from H. pylori infection. A decrease in pepsinogen II level has been suggested as a reliable marker to confirm the successful eradication of infection. These researchers evaluated the potential role of pepsinogens I and II, gastrin-17 and H. pylori antibodies in confirming successful eradication. A total of 42 patients (25 women, 17 men), mean age of 45 years (range of 23 to 74), were enrolled. Pepsinogens I and II, gastrin-17 and H. pylori IgG antibodies were measured in plasma samples using an ELISA test (Biohit, Oyj., Finland) before the eradication and 4 weeks after completing the treatment. The success of eradication was determined by a urea breath test. Eradication was successful in 31 patients (74 %) and unsuccessful in 11 patients (26 %). Pepsinogen II decreased significantly in both the successful (p = 0.029) and unsuccessful (p = 0.042) eradication groups. Pepsinogen I decreased significantly in the successful (p = 0.025) but not the unsuccessful (p = 0.29) eradication group. The pepsinogen I/II ratio increased in the successful eradication group (p = 0.0018) but not in the group in which treatment failed (p = 0.12). There were no differences in gastrin-17 or H. pylori antibody values. The authors concluded that a decrease in pepsinogen II levels cannot be used as a reliable marker for the successful eradication of H. pylori 4 weeks after the completion of treatment. The increase in pepsinogen I/II ratio reflects differences in pepsinogen production following the eradication irrespective of improvement in atrophy.
Urea breath test, C-14 (isotopic); acquisition for analysis
Helicobacter pylori; breath test analysis for urease activity, non-radioactive isotope (eg, C-13)
Helicobacter pylori, stool
CPT codes not covered for indications listed in the CPB:
Immunoassay for analyte other than infectious agent antibody or infectious agent antigen; quantitative, by radioimmunoassay (eg, RIA) [plasma pepsinogen II testing]
Infectious agent detection by nucleic acid (DNA or RNA); respiratory virus (eg, adenovirus, influenza virus, coronavirus, metapneumovirus, parainfluenza virus, respiratory syncytial virus, rhinovirus), includes multiplex reverse transcription, when performed, and multiplex amplified probe technique, multiple types or subtypes, 6-11 targets
ICD-9 codes covered if selection criteria are met:
Intestinal infection due to Campylobacter
Other specified bacterial infection, Helicobacter pylori (H. pylori)
531.00 - 531.91
532.00 - 532.01
Duodenal ulcer, acute with hemorrhage
532.10 - 532.11
Duodenal ulcer, acute with perforation
532.20 - 532.21
Duodenal ulcer, acute with hemorrhage and perforation
Duodenal ulcer, acute without mention of hemorrhage or perforation, with obstruction
532.40 - 532.41
Duodenal ulcer, chronic or unspecified with hemorrhage
532.50 - 532.51
Duodenal ulcer, chronic or unspecified with perforation
532.60 - 532.61
Duodenal ulcer, chronic or unspecified with hemorrhage and perforation
Duodenal ulcer, chronic without mention of hemorrhage or perforation, with obstruction
Duodenal ulcer, unspecified as acute or chronic, without mention of hemorrhage or perforation, with obstruction
533.00 - 533.91
Peptic ulcer, site unspecified
534.00 - 534.91
Dyspepsia and other specified disorders of function of stomach
ICD-9 codes not covered for indications listed in the CPB:
280.0 - 285.9
290.0 - 290.9
560.0 - 560.9
Intestinal obstruction without mention of hernia
Perforation of intestine
Loss of weight
Adverse effects of local anti-infectives and anti-inflammatory drugs
Special screening examination for other specified bacterial and spirochetal diseases
Other ICD-9 codes related to the CPB:
535.00 - 535.61
Gastritis and duodenitis, with or without hemorrhage
Long-term (current) use of antibiotics
The above policy is based on the following references:
National Institutes of Health (NIH). Helicobacter pylori in peptic ulcer disease. NIH Consensus Statement. Rockville, MD: NIH; January 1994:1-23.
Soll AH. Consensus conference: Medical treatment of peptic ulcer disease. Practice guidelines. Practice Parameters Committee of the American College of Gastroenterology. JAMA. 1996;275(8):622-629.
Cutler AF. Testing for Helicobacter pylori in clinical practice. Am J Med. 1996;100(5A):35S-41S.
Rune SJ. Diagnosis of Helicobacter pylori infection. When to use which test and why. Scand J Gastroenterol Suppl. 1996;215:63-65.
Klein PD, Malaty HM, Martin RF, et al. Noninvasive detection of Helicobacter pylori infection in clinical practice: The 13C urea breath test. Am J Gastroenterol. 1996;91(4):690-694.
Desroches JJ, Lahaie RG, Picard M, et al. Methodological validation and clinical usefulness of carbon-14-urea breath test for documentation of presence and eradication of Helicobacter pylori infection. J Nucl Med. 1997;38(7):1141-1145.
Nakamura RM. Laboratory tests for the evaluation of Helicobacter pylori infections. J Clin Lab Anal. 2001;15(6):301-307.
Braden B, Caspary WF. Detection of Helicobacter pylori infection: When to perform which test? Ann Med. 2001;33(2):91-97.
Meurer LN, Bower DJ. Management of Helicobacter pylori infection. Am Fam Physician. 2002;65(7):1327-1336.
Howden CW, Hunt RH. Guidelines for the management of Helicobacter pylori infection. Am J Gastroentrol. 1998;93(12):2330-2338. Available at: http://www.acg.gi.org/physicianforum/guides/hpguide.html. Accessed August 21, 2003.
Roderick P, Davies R, Raftery J, et al. The cost-effectiveness of screening for Helicobacter pylori to reduce mortality and morbidity from gastric cancer and peptic ulcer disease: A discrete-event simulation model. Health Technol Assess. 2003;7(6):1-86.
Institute For Clinical Systems Improvement (ICSI). Dyspepsia. Health Care Guideline. Bloomington, MN: ICSI; January 2003.Availableat:http://www.icsi.org/knowledge/detail.asp?catID=29&itemID=171. Accessed August 21, 2003.
Gisbert JP, Pajares JM. Diagnosis of Helicobacter pylori infection by stool antigen determination: A systematic review. Am J Gastroenterol. 2001;96(10):2829-2838.
Gisbert JP, Pajares JM. Stool antigen test for the diagnosis of Helicobacter pylori infection: A systematic review. Helicobacter. 2004;9(4):347-368.
Gisbert JP, Pajares JM. Review article: C-13-urea breath test in the diagnosis of Helicobacter pylori infection. A critical review. Aliment Pharmacol Therapeut. 2004;20(10):1001-1017.
National Institute for Clinical Excellence (NICE). Management of dyspepsia in adults in primary care. Clinical Guideline 17. London, UK: NICE; 2004.
American Gastroenterological Association (AGA). American Gastroenterological Association Medical Position Statement: Evaluation of Dyspepsia. Gastroenterol. 2005;129:1753-1755.
American Gastroenterological Association (AGA). American Gastroenterological Association Technical Review on the Evaluation of Dyspepsia. Gastroenterol. 2005;129:1756-1780.
Erickson L. The 13C-urea breath test for detection of Helicobacter pylori: Potential applications in Quebec. Technology Brief. AETMIS 05-05 RE. Montreal, QC: Agence d'Evaluation des Technologies et des Modes d'Intervention en Sante (AETMIS); December 2005:1-116. Available at: http://www.aetmis.gouv.qc.ca/. Accessed January 31, 2006.
Paimela HM, Oksala NK, Kaariainen IP, et al. Faecal antigen tests in the confirmation of the effect of Helicobacter eradication therapy. Ann Med. 2006;38(5):352-356.
Dondi E, Rapa A, Boldorini R, et al. High accuracy of noninvasive tests to diagnose Helicobacter pylori infection in very young children. J Pediatr. 2006;149(6):817-821.
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.
Vakil N, Fendrick AM. How to test for Helicobacter pylori in 2005. Cleve Clin J Med. 2005;72 Suppl 2:S8-S21.
Vakil N, Megraud F. Eradication therapy for Helicobacter pylori. Gastroenterology. 2007;133(3):985-1001.
Meridian Bioscience, Inc. Premiere Platinum HpSA enzyme immunoassay for the detectin of Helicobacter pylori antigens in stool specimens for diagnosis and monitoring. Package Insert. SN11256. Cincinnati, OH: Meridian Bioscience; revised January 2001. Available at: http://www.meridianbioscience.com. Accessed January 21, 2008.
Meretek Diagnostics Group of Otsuka America Pharmaceutical, Inc. BreathTek urea breath test for H. pylori. Package Insert. Part No. 0507L-0027A. Rockville, MD: Meretek; revised September 2007. Available at: http://www.meretek.com/. Accessed January 21, 2008.
Stenström B, Mendis A, Marshall B. Helicobacter pylori -- the latest in diagnosis and treatment. Aust Fam Physician. 2008;37(8):608-612.
Buzás GM, Széles I. Interpretation of the 13C-urea breath test in the choice of second- and third-line eradication of Helicobacter pylori infection. J Gastroenterol. 2008;43(2):108-114.
Mundy L, Purins A, Hiller JE. The targeted screening and eradication of Helicobacter pylori. Horizon Scanning Prioritising Summary. Adelaide, SA: Adelaide Health Technology Assessment (AHTA); 2008.
Mundy L, Purins A, Hiller JE. Rapid test for Helicobacter pylori diagnosis of patients presenting with symptoms of dyspepsia. Horizon Scanning Prioritising Summary. Adelaide, SA: Adelaide Health Technology Assessment (AHTA); 2008.
Mundy L, Braunack-Mayer A, Hiller JE. Rapid testing and targeted population screening for Helicobacter pylori. Adelaide, SA: Adelaide Health Technology Assessment (AHTA); 2009.
Calvet X, Sánchez-Delgado J, Montserrat A, et al. Accuracy of diagnostic tests for Helicobacter pylori: A reappraisal. Clin Infect Dis. 2009;48(10):1385-1391.
Elitsur Y, Tolia V, Gilger MA, et al. Urea breath test in children: The United States prospective, multicenter study. Helicobacter. 2009;14(2):134-140.
Atreja A, Fu AZ, Sanaka MR, Vargo JJ. Non-invasive testing for Helicobacter pylori in patients hospitalized with peptic ulcer hemorrhage: A cost-effectiveness analysis. Dig Dis Sci. 2010;55(5):1356-1363.
Guarner J, Kalach N, Elitsur Y, Koletzko S. Helicobacter pylori diagnostic tests in children: Review of the literature from 1999 to 2009. Eur J Pediatr. 2010;169(1):15-25.
Bytzer P, Dahlerup JF, Eriksen JR, et al; Danish Society for Gastroenterology. Diagnosis and treatment of Helicobacter pylori infection. Dan Med Bull. 2011;58(4):C4271.
Roubaud Baudron C, Letenneur L, Langlais A, et al; Personnes Agées QUID Study. Does Helicobacter pylori infection increase incidence of dementia? The Personnes Agées QUID Study. J Am Geriatr Soc. 2013;61(1):74-78.
Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108(3):308-328.
Lopes AI, Vale FF, Oleastro M. Helicobacter pylori infection - recent developments in diagnosis. World J Gastroenterol. 2014;20(28):9299-9313.
Crow SE. Indications and diagnostic tests for Helicobacter pylori infection. UpToDate [serial online]. Waltham, MA: UpToDate; reviewed November 2014.
Leja M, Lapina S, Polaka I, et al. Pepsinogen testing for evaluation of the success of Helicobacter pylori eradication at 4 weeks after completion of therapy. Medicina (Kaunas). 2014;50(1):8-13.
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Loy CT, Irwig LM, Katelaris PH, Talley NJ. Do commercial serology kits for Helicobacter pylori infection differ in accuracy? Am J Gastroenterol. 1996;91:1138-1144.
Roberts AP, Childs S, Rubin G, de Wit NJ. Tests for Helicobacter pylori infection: A critical appraisal from primary care. Family Practice. 2000;17(suppl 2):S12-S20.
Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.