Clinical Policy Title: Noninvasive testing for H. pylori

Transcription

1 Clinical Policy Title: Noninvasive testing for H. pylori Clinical Policy Number: Effective Date: January 1, 2016 Initial Review Date: August 19, 2015 Most Recent Review Date: July 3, 2018 Next Review Date: July 2019 Related policies: Policy contains: Helicobacter pylori (H. pylori) infection. Urea breath testing. Stool antigen testing or fecal antigen testing Anti-reflux devices for gastrointestinal reflux disease ABOUT THIS POLICY: Select Health of South Carolina has developed clinical policies to assist with making coverage determinations. Select Health of South Carolina s clinical policies are based on guidelines from established industry sources, such as the Centers for Medicare & Medicaid Services (CMS), state regulatory agencies, the American Medical Association (AMA), medical specialty professional societies, and peerreviewed professional literature. These clinical policies along with other sources, such as plan benefits and state and federal laws and regulatory requirements, including any state- or plan-specific definition of medically necessary, and the specific facts of the particular situation are considered by Select Health of South Carolina when making coverage determinations. In the event of conflict between this clinical policy and plan benefits and/or state or federal laws and/or regulatory requirements, the plan benefits and/or state and federal laws and/or regulatory requirements shall control. Select Health of South Carolina s clinical policies are for informational purposes only and not intended as medical advice or to direct treatment. Physicians and other health care providers are solely responsible for the treatment decisions for their patients. Select Health of South Carolina s clinical policies are reflective of evidence-based medicine at the time of review. As medical science evolves, Select Health of South Carolina will update its clinical policies as necessary. Select Health of South Carolina s clinical policies are not guarantees of payment. Coverage policy Select Health of South Carolina considers the use of noninvasive diagnostic testing for Helicobacter pylori (H. pylori) infection to be clinically proven, and therefore medically necessary when any of the following criteria are met: 1. Peptic ulcer disease is present. 2. Member has a past history of peptic ulcer disease is documented. 3. Low-grade gastric mucosa-associated lymphoid tissue lymphoma is documented. 4. Member has a history of endoscopic resection of early gastric cancer. 5. Members with peptic ulcer disease given upper endoscopy (via biopsy). 6. Members initiating chronic treatment with nonsteroidal anti-inflammatory drugs. 7. Members with unexplained iron deficiency anemia, despite an appropriate evaluation. 8. Adult members have documented idiopathic thrombocytopenic purpura (Chey, 2017). Testing for H. pylori can be considered for any of the following: 1. Members taking low-dose, long-term aspirin (to reduce ulcer bleeding). 2. Members under age 60 with uninvestigated dyspepsia and without alarm features (anemia, 1

2 acute onset of total dysphagia, hematemesis, melena, persistent vomiting, and weight loss over five percent (ICSI, 2004). Retesting for H pylori can be performed using urea breath tests, but not stool samples (NICE, 2014). Limitations: All other uses of noninvasive diagnostic testing for H. pylori are not medically necessary, including: 1. Members with topical symptoms of gastrointestinal reflux disease with no history of pelvic ulcer disease. 2. Asymptomatic members with a family history of gastric cancer, or with lymphocytic gastritis, hyperplastic gastritis, hyperplastic gastric polyps, or hyperemesis gravidarum (Chey, 2017). Alternative covered services: Clinical evaluation by physicians and appropriate standard diagnostic procedures. Background H. pylori is a gram-negative bacterium found in the luminal surface of the gastric epithelium and responsible for the inflammation of the underlying mucosa of the gastric epithelium. This bacterium is unique in its ability to survive in the acidic environment of the stomach because of its high urease enzyme that converts the urea of gastric juice to basic ammonia and carbon dioxide activity. H. pylori infection can be a cause of chronic gastritis, peptic ulcer disease and gastric malignancy. The disease usually is acquired in childhood (Chey, 2017). Estimates of the prevalence of H. pylori infection indicate that at least 50 percent of the world s population is affected (Tonkic, 2012). Within the United States, the prevalence estimate is about 50 percent, and is substantially lower among non-hispanic whites than for other racial and ethnic groups. Socially disadvantaged populations have elevated prevalence rates (Chey, 2017).. The majority of individuals infected with H. pylori does not display clinically significant complications and will not require treatment (Tonkic, 2012). Signs, symptoms, and conditions associated with H. pylori: Recognition, testing, and treatment for H. pylori can be difficult because of the variety of non-specific gastrointestinal signs and symptoms at presentation. H. pylori causes many symptoms of indigestion or dyspepsia defined as long-term pain in the upper abdomen, which can also be linked to non-ulcer dyspepsia or gastroesophageal reflux disease. The most frequent features reported in patients with H. pylori are heartburn or epigastric pain, burping, bloating or post-prandial fullness, nausea, vomiting, slow digestion or delayed gastric emptying, and acid hyper secretion. 2

3 H. pylori bacteria inflame the mucosa lining triggering an increase in gastrin, a hormone that stimulates stomach acid release. Elevated levels of gastrin cause excess acid secretion from all areas of the stomach (even those areas not infected). In turn, the high acidity, which further damages the mucosa lining of the stomach, causes ulceration and metaplasia and increases the risk for additional infection by the H. pylori bacteria. There is a strong association between the H. pylori infection, gastric cancer and gastric MALT lymphomas. Eradication of the infection provides a cure to 80 percent of duodenal ulcers unrelated to non-steroidal anti-inflammatory drugs and reduces progression of atrophic gastritis and localized gastric mucosa-associated tissue lymphoma. Diagnosis of H. pylori: Proper eradication treatment can resolve symptoms of dyspepsia, if it is related to an underlying ulcer disease caused by H. pylori. However, screening is not recommended in all patients with symptoms of dyspepsia, as empiric treatment with acid suppression is effective among some populations. Further, many conditions, including gastroesophageal reflux disease and nonlcer dyspepsia, are not associated with H. pylori. There are numerous different diagnosis tests for H. pylori including endoscopy, serology, urea breath testing, and stool antigen testing. These tests are used for diagnosis and evaluation of eradication after treatment. The most invasive diagnostic tool is endoscopy, which entails a biopsy of cells from the prepyloric region or fundic region. Endoscopy is not required for diagnosis and is not often the test of choice to confirm diagnosis. Serologic tests identify the immunoglobulin G (IgG) antibodies response to H. pylori bacteria within an individual s blood. This type of testing has relatively low sensitivity at 85 percent and specificity at 79 percent. The results can be reported as equivocal. It is not useful in testing for eradication of the bacteria, as antibodies may persist for months beyond treatment despite eradication of the bacteria. A common noninvasive test is urea breath testing; this test relies on the bacteria s ability to convert carbon dioxide to urea. Urea breath testing centers on labeling isotopes of carbon dioxide urea ingested by the patient. The test compares a baseline sample with the post administration level of carbon dioxide using a mass spectrometer or infrared spectrophotometer. This test is commonly used to measure the success of treatment and is widely used, as the samples are easy to collect and can be sent to central laboratories. This reduces the need for expensive equipment at individual providers. Confirmation of diagnosis and eradication is also possible with stool antigen testing (or fecal antigen testing). Identifying H. pylori-specific antigens using either monoclonal or polyclonal antibodies detects the presence of H. pylori. Compared to urea breath testing, monoclonal testing is more sensitive and specific, less expensive, less affected by proton pump inhibitor use, and requires less equipment. Several guidelines on appropriateness of H. pylori testing have been produced by professional groups. 3

4 The National Institute for Health and Clinical Excellence guideline endorses use of urea breath tests or stool antigen tests, or a locally validated laboratory serology. When retesting is done, the organization endorses using a urea breath test, but not stool testing based on lack of evidence (NICE, 2014). The Institute for Clinical Systems Improvement guideline defines the alarm features in patients that should be present as part of the decision to test patients with dyspepsia for H. pylori. These features include (ICSI, 2004): 1. Anemia (7 10 days). 2. Acute onset of total dysphagia (within one day). 3. Hematemesis (within one day if patient is ill). 4. Melena (within one day if patient is ill). 5. Persistent vomiting (7 10 days). 6. Involuntary weight loss of five percent or more (7 10 days). In 2017, the American College of Gastroenterology issued a detailed and guideline on H. pylori epidemiology, testing, diagnosis, and management an update from the group s guideline of a decade earlier. The College defined the appropriate criteria when patients with dyspepsia should be tested, could be tested, or should not be tested for H. pylori, listed in the Coverage section of this policy (Chey, 2017). Searches Select Health of South Carolina searched PubMed and the databases of: UK National Health Services Centre for Reviews and Dissemination. Agency for Healthcare Research and Quality s National Guideline Clearinghouse and other evidence-based practice centers. The Centers for Medicare & Medicaid Services (CMS). We conducted searches on May 15, Search terms were: Helicobacter pylori, and diagnosis, detection, accuracy, sensitivity, specificity, and noninvasive. We included: Systematic reviews, which pool results from multiple studies to achieve larger sample sizes and greater precision of effect estimation than in smaller primary studies. Systematic reviews use predetermined transparent methods to minimize bias, effectively treating the review as a scientific endeavor, and are thus rated highest in evidence-grading hierarchies. Guidelines based on systematic reviews. Economic analyses, such as cost-effectiveness, and benefit or utility studies (but not simple cost studies), reporting both costs and outcomes sometimes referred to as efficiency studies which also rank near the top of evidence hierarchies. 4

5 Findings A Cochrane review of 101 studies (n=11,003) compared sensitivity, and rate of false positive H pylori results per 1000 tests, for four types of non-invasive tests. Results were a sensitivity of 0.83 and 89 false positives for stool antigen tests, 0.94 and 30 for urea breath test using carbon-13, 0.92 and 42 for urea breath test using carbon-14, and 0.84 and 86 for urea breath test using carbon-14 serology (Best, 2018). These results upheld an earlier review of 19 studies that found high sensitivity and specificity for urea breath testing using carbon-13, superior to those of stool antigens (Ling, 2013). In 2012, the U.S. Food and Drug Administration approved the first H. pylori test for children, age The test, BreathTek urea breath testing, had been approved for adults in 1996, and followed a metaanalysis of 48 studies of at least 30 children each, showing high sensitivity and specificity, both 97 percent (Leal, 2011). The table below summarizes the findings from four systematic reviews of the clinical validity of multiple types of noninvasive H. pylori diagnostic tests have been published in the medical literature (Childs, 2000; Gisbert, 2006; Ling, 2013; Ferwana, 2015). Table 1. Pooled estimates of sensitivity and specificity of noninvasive tests for H. pylori diagnosis Type of Test Source Sensitivity % (95% CI) Specificity% (95% CI) Serological Childs (2000) Ling (2013) 92.2 ( ) 71.7 ( ) ICSI (2004) Urea breath Childs (2000) testing Calvet (2009) 90.3 (83 95) 89.5 (81 95) Ling (2013) 95 ( ) 91.6 ( ) Ferwana (2015) 96 (95 97) 93 (91 94) ICSI (2004) Monoclonal stool NICE (2009) Chey (2007) Gisbert (2006) 95 (93 96) 97 (94 98) MAS (2010) 85.1 ( ) Polyclonal stool Calvet (2009) 90.3 (83 95) 93 (84 97) Chey (2007) Gisbert (2006) 83 (80 85) 96 (94 97) 5

6 Stool testing (with no ICSI (2004) differentiation to type) The second table summarizes the results of four systematic reviews of non-invasive testing, one randomized control trial comparing diagnostic tests and four professional guidelines related to diagnosis and treatment of H. pylori. Serologic testing for H. pylori: The results from available systematic reviews indicate that serologic testing for antibodies linked to H. pylori infections demonstrate high sensitivity and specificity for initial diagnosis. These serologic tests are especially useful in areas with high prevalence of the infection, but antibodies specifying this infection can differ locally, and their accuracy can range (Childs, 2000). Because of the cost-effectiveness and ease of blood tests, this is a first line diagnostic measure in some places, but confirmation requires additional testing if the area has a low prevalence (Ling, 2013; Chey, 2007). Further serologic testing is unreliable for post-treatment eradication verification, as antibodies for H. pylori may remain in the blood for six to 12 months after eradication (Childs, 2000). Urea breath testing: The evidence for urea breath testing for screening for H. pylori in a test-and-treat strategy is based on three systematic reviews (Ling, 2013; Ferwana, 2015; Childs, 2006) and professional guidelines. As shown in the table above, urea breath testing has high sensitivity and specificity, both > 90 percent and can also be used to evaluate if eradication treatments were successful. Urea breath testing is considered the gold standard for post-treatment testing (Childs, 2000). This test can be prohibitively expensive and some facilities may not have the materials onsite to perform. Urea breath testing in women and children should only use carbon-13 isotopes, as they provide lower doses of radiation. The most recent systematic reviews continue to show high accuracy levels of these tests to diagnose H. pylori. Urine tests in 23 studies (n=4963) show pooled sensitivity and specificity of 83 and 89 percent (Gong, 2017). A meta-analysis of 18 studies of adults with dyspepsia found that the 14 C-urea breath test had sensitivity and specificity rates of 96 and 93 percent (Zhou, 2017). Another meta-analysis on the ability of magnifying endoscopy to predict H. pylori infections included 18 studies (n=1897); sensitivity and specificity were 89 and 82 percent, respectively (Qi, 2016). Accuracy of H. pylori testing in children has also been addressed in the literature. One review of the stool antigen test in children included 45 studies (n=5931), and documented sensitivity and specificity rates of 92.1 and 94.1 percent (Zhou, 2014). Some systematic reviews address accuracy of H. pylori testing for specific subpopulations. In a review of persons after partial gastrectomy, sensitivity and specificity varied for urea breath test (0.77 and 0.89, nine studies), rapid unrease test (0.79 and 0.94, seven studies), and histology (0.93 and 0.85, three 6

7 studies (Tian, 2012). Policy updates: A total of one guideline/other and four peer-reviewed references were added to, and one guideline/other and one peer-reviewed reference removed from, this policy in May, Summary of clinical evidence: Citation Best (2018) Content, Methods, Recommendations Key points: Accuracy of various non-invasive methods of H. pylori testing Cochrane review of 101 studies (n=11,009), 53.1% positive for H. pylori. Sensitivity varied for stool antigen test (0.83), urea breath test using C-13 (0.94), urea breath test using C-14 (0.92), and urea breath test serology using C-14 (0.84). Estimated false positives per 1,000 tests were 89 for stool antigen test, 30 for urea breath test using C-13, 42 for urea breath test using C-13, and 86 for urea breath test (UBT) serology using C-14. Ferwana (2015) UBT Ling (2013) Carbon-13 UBT in uninvestigated dyspepsia Gisbert (2006) Fecal antigen test Childs (2000) Key points: Systematic review of 3,999 patients for the accuracy of UBT (Level B). Twenty-three studies pooled found UBT testing of Se = 96% and Sp = 93%. UBT showed significant discrimination ability between infected and non-infected states. May provide better comprehensive results than endoscopy because eliminate error with endoscopic biopsy when H. pylori has inconsistent distribution and does not rely on pathologist. Oral flora s urease activity may impact accuracy of results. Key points: Systematic review of 21 studies with 4,536 patients (Level A). Serology and UBT are comparably sensitive, but UBT is more sensitive. Clinically, serological is a first-line diagnostic test in the United States; UBT or SAT is also considered first-line diagnostic methods. Lack of standards in processing of UBT creates variability in results. Key points: Systematic review of 2,499 patients (Level A). Pre-treatment pooled Se = 94%, Sp = 97%, monoclonal FAT had higher sensitivity (Se = 95%, Sp = 96%) versus polyclonal test (Se = 83%, Sp = 96%). Post-treatment evaluation shows distinct difference between monoclonal (Se=91%, Sp=95%) and polyclonal (Se = 76%, SP = 95%), as monoclonal is more sensitive. Monoclonal testing shows better distinction between infection and non-infection, with no equivocal response. Key points: Noninvasive and post treatment testing Systematic review. Serology is not accurate for all patient populations and requires local validation; can have six to 12-month lag time in detecting changes in infection status, although may be the cheapest option. UBT is non-invasive test of choice. 7

8 Citation Content, Methods, Recommendations Post-treatment testing is required in those with severe or complicated DU or GU, MALT lymphoma, and early gastric cancer. H. pylori treatment guided by testing is preferred choice, although cost savings are slow to see. Can lower cost of treatment further by using empiric treatment where there is high prevalence of infection and DU. References Professional society guidelines/other: Blazek N. FDA approves H. pylori breath test for children. Clinical Advisor, February 24, Accessed May 16, Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: treatment of helicobacter pylori infection. Bethesda MD: American College of Gastroenterology (ACG), Accessed May 16, Institute for Clinical Systems Improvement (ICSI) Health Care Guideline: Dyspepsia and GERD. Bloomington MN: ICSI, I% pdf. Accessed May 16, Ling D. Carbon-13 urea breath test for Helicobacter pylori infection in patients with uninvestigated ulcerlike dyspepsia: an evidence-based analysis. Ont Health Technol Assess Ser. 2013; 13(19): National Institute for Health and Clinical Excellence (NICE). Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management. NICE; last updated November Accessed May 16, 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): Peer-reviewed references: Best LM, Takwoingi Y, Siddique S, et al. Non-invasive diagnostic tests for Helicobacter pylori infection. Cochrane Database Syst Rev Mar 15;3:CD Doi: / CD pub2. Calvet X, Sánchez-delgado J, Montserrat A, et al. Accuracy of diagnostic tests for Helicobacter pylori: a reappraisal. Clin Infect Dis. 2009; 48(10): Childs S, Roberts A, Meinecke-Schmidt V, dewit N, Rubin G. The management of Helicobacter pylori infection in primary care: a systematic review of the literature. Family Practice. 2000; 17(suppl 2): S6. Fashner J, Gitu AC. Diagnosis and treatment of peptic ulcer disease and H. pylori Infection. Am Fam Physician. 2015; 91(4):

9 Ferwana M, Abdulmajeed I, Alhajiahmed A, et al. Accuracy of urea breath test in Helicobacter pylori infection: meta-analysis. World J Gastroenterol. 2015; 21(4): Gisbert JP, De la Morena F, Abraira V. Accuracy of monoclonal stool antigen test for the diagnosis of H. pylori infection: a systematic review and meta-analysis. Am J Gastroenterol. 2006; 101(8): Gong Y, Li Q, Yuan Y. Accuracy of testing for anti-helicobacter pylori IgG in urine for H. pylori infection diagnosis: a systematic review and meta-analysis. BMJ Open. 2017; 7(4): e Leal YA, Cedillo-Rivera R, Simon JA, Velazquez JR, Flores LL, Torres J. Utility of stool sample-based tests for the diagnosis of Helicobacter pylori infection in children. J Pediatr Gastroenterol Nutr. 2011;52(6): Ling D. Carbon-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;13(19):1 30. Qi Q, Guo C, Ji R, Li Z, Zuo X, Li Y. Diagnostic performance of magnifying endoscopy for Helicobacter pylori infection: a meta-analysis. PLoS One. 2016; 11(12): Doi: /journal.pone Tian XY, Zhu H, Zhao J, She Q, Zhang GX. Diagnostic performance of urea breath test, rapid urea test, and histology for Helicobacter pylori infection in patients with partial gastrectomy: a meta-analysis. J Clin Gastroenterol. 2012;46(4): Tonkic A, Tonkic M, Lehours P, Mégraud F. Epidemiology and diagnosis of Helicobacter pylori infection. Helicobacter. 2012; 17 Suppl 1: 1 8. Zhou Q, Li L, Ai Y, Pan Z, Guo M, Han J. Diagnostic accuracy of the 14C-urea breath test in Helicobacter pylori infections: a meta-analysis. Wien Klin Wochenschr. 2017; 129(1-2): Zhou X, Su J, Xu G, Zhang G. Accuracy of stool antigen test for the diagnosis of Helicobacter pylori infection in children: a meta-analysis. Clin Res Hepatol Gastroenterol. 2014; 38(5): CMS National Coverage Determinations (NCDs): No NCDs identified as of the writing of this policy. Local Coverage Determinations (LCDs): No LCDs identified as of the writing of this policy. Commonly submitted codes Below are the most commonly submitted codes for the service(s)/item(s) subject to this policy. This is not an exhaustive list of codes. Providers are expected to consult the appropriate coding manuals and bill accordingly. 9

10 CPT Code Description Comment Helicobacter pylori; breath test analysis for urease activity, non-radioactive isotope Helicobacter pylori, stool ICD-10 Code Description Comment A04.8 Helicobacter pylori (H. pylori) B96.81 H. pylori as the cause of diseases classified elsewhere C88.4 MALT lymphoma K27.9 Peptic ulcer, site unspecified R10.13 Dyspepsia HCPCS Level II Code N/A Description Comment 10