What is the recommended testing strategy for Helicobacter pylori infection in adults, including first‑line non‑invasive tests and indications for endoscopic biopsy?

Testing for H. Pylori

For adults under 50 years without alarm symptoms, use the ¹³C-urea breath test or laboratory-based monoclonal stool antigen test as first-line non-invasive testing; for those ≥50 years or with any alarm features, proceed directly to endoscopy with invasive testing. 1, 2, 3

First-Line Non-Invasive Testing Strategy

Preferred Tests

• The ¹³C-urea breath test (UBT) is the most accurate non-invasive diagnostic method, with sensitivity of 94-97% and specificity of 95-97.7%. 1, 3 This test detects active infection by measuring urease activity and requires a 6-hour fast before testing. 2

• Laboratory-based monoclonal stool antigen testing achieves comparable accuracy to UBT, with sensitivity and specificity of approximately 93%. 1, 3 This test directly detects bacterial antigens and indicates active infection. 2

• Rapid in-office immunochromatographic stool tests must be avoided—their accuracy drops to only 80-81% and they are explicitly not recommended. 1, 2

Tests to Avoid for Initial Diagnosis

• Serology has inadequate accuracy (averaging only 78%, range 68-82%) and cannot distinguish active infection from past exposure. 1, 2 Antibodies persist for months to years after eradication, making serology unreliable for confirming current infection. 1, 2

• Serology may only be considered when recent PPI or antibiotic use prevents medication washout and testing cannot be delayed, or in contexts of gastric atrophy, malignancy, or ulcer bleeding where bacterial load is low. 1, 2

Age-Based Testing Algorithm

Patients Under 50 Years Without Alarm Symptoms

• Use the "test-and-treat" strategy: perform UBT or monoclonal stool antigen test, then treat if positive without requiring endoscopy. 1, 2, 3 This approach reduces unnecessary endoscopies by 62% while maintaining equivalent safety and symptom resolution. 1

• Before non-invasive testing, exclude family history of gastric cancer—this mandates specialist referral regardless of age. 1

Patients ≥50 Years or With New-Onset Dyspepsia

• Proceed directly to endoscopy with invasive testing because gastric cancer incidence rises markedly after age 50 (≈19 cases/100,000 men and 9 cases/100,000 women in the European Community). 1

• In regions with higher gastric cancer prevalence, lower the age threshold for endoscopic referral. 1

Indications for Immediate Endoscopy (Any Age)

Any patient with alarm symptoms requires direct endoscopy, bypassing non-invasive testing: 1, 3

• Anemia 1
• Unintentional weight loss 1
• Dysphagia (difficulty swallowing) 1
• Palpable abdominal mass 1
• Gastrointestinal bleeding 1
• Progressive or recurrent vomiting 1
• Malabsorption 1

Critical Medication Washout Requirements

Before Any Testing (Except Serology)

• Stop proton pump inhibitors (PPIs) for at least 2 weeks before performing UBT, stool antigen test, rapid urease test, histology, or culture. 1, 2, 3 PPIs suppress bacterial load and cause 10-40% false-negative rates across all these methods. 1

• Stop antibiotics and bismuth compounds for at least 4 weeks before testing. 1, 3

• Serology is the only test unaffected by ongoing PPI therapy and can be performed without washout. 1 However, its poor accuracy limits its utility to specific circumstances described above.

Common Pitfall

Failure to observe medication washout periods is the leading cause of false-negative results. 1 Do not order H. pylori testing while patients are on PPIs unless serology is deliberately chosen for the specific limited indications. 1

Invasive Testing During Endoscopy

When Endoscopy Is Performed

• Rapid urease test (RUT) provides quick results during endoscopy, with pre-treatment sensitivity of 80-95% and specificity of 95-100%. 2, 3 However, RUT requires approximately 10⁴ organisms for positive results—lower bacterial densities yield false negatives. 1, 3

• Histology with modified Giemsa staining achieves 90-95% sensitivity when performed correctly, with specificity of 95-98%. 1 Immunohistochemistry is the gold standard when results are equivocal. 1

• Obtain at least two biopsy samples from both antrum and body—single biopsies miss infections due to patchy colonization. 1, 2, 3

• Culture with antimicrobial susceptibility testing is particularly valuable in regions with high clarithromycin resistance (>15-20%) or after treatment failure. 1, 3

Confirmation of Eradication After Treatment

• Test for eradication at least 4 weeks after completing therapy using UBT or monoclonal stool antigen test—never use serology. 1, 2, 3 Antibodies remain elevated after H. pylori elimination, making serology useless for confirming eradication. 1, 2

• Ensure the same medication washout periods apply: stop PPIs for ≥2 weeks and antibiotics/bismuth for ≥4 weeks before confirmation testing. 1, 3

Key Pitfalls to Avoid

• Do not use rapid in-office stool antigen kits—always specify laboratory-based monoclonal assays. 1, 2

• Do not employ serology panels (IgG/IgA/IgM) as they add no diagnostic value beyond validated IgG testing. 1

• Do not test patients whose predominant presentation is typical irritable bowel syndrome rather than dyspepsia. 1

• Do not perform single antral biopsies during endoscopy—they yield positive results in only 90% of infected stomachs. 1