Which non‑invasive test should be ordered 4–6 weeks after completing Helicobacter pylori therapy, after stopping proton pump inhibitors, H2‑blockers, and antibiotics for at least two weeks, to confirm eradication?

Confirming H. pylori Eradication After Treatment

Order either a urea breath test (UBT) or a validated monoclonal stool antigen test at least 4 weeks after completing therapy, ensuring the patient has stopped PPIs for at least 2 weeks, antibiotics and bismuth for at least 4 weeks, and has fasted for 6 hours before testing. 1, 2

Recommended Non-Invasive Tests

Both tests have equivalent accuracy and can be used interchangeably:

• Urea breath test (UBT): Sensitivity 94.7–97%, specificity 95–100% 1, 2
• Validated monoclonal stool antigen test: Sensitivity and specificity >90% 1, 2

The American Gastroenterological Association endorses both methods as equally accurate alternatives for confirming eradication. 1 The stool antigen test offers a particular advantage when patients must continue PPI therapy, as it may be less affected by acid suppression than the UBT. 1

Critical Pre-Testing Requirements

Medication washout periods are mandatory to avoid false-negative results:

• Stop PPIs: At least 2 weeks before testing (preferably 7–14 days) 1, 2
• Stop antibiotics and bismuth: At least 4 weeks before testing 1, 2
• Fasting: At least 6 hours before the test 1, 2

The European Society of Gastrointestinal Endoscopy emphasizes that PPIs decrease gastric bacterial load and can cause false-negative results if not discontinued appropriately. 2

Timing of Test of Cure

Perform testing at least 4 weeks after completing H. pylori treatment. 1, 2

Testing before 4 weeks yields unreliable results because the gastric mucosa requires this recovery period, and earlier testing may show false-negative results from temporary bacterial suppression rather than true eradication. 1, 2 The European Helicobacter Study Group notes that relapse in the first 6 months primarily represents recrudescence of the same infection rather than reinfection, making early testing particularly unreliable. 1

Special Clinical Scenarios Requiring Modified Timing:

• Bleeding peptic ulcers: Delay testing to 4–8 weeks after the bleeding episode 1, 2
• Gastric MALT lymphoma: Test at least 6 weeks after eradication therapy 2

Tests That Should NOT Be Used

Serology has no role in determining eradication success because antibody levels remain elevated for 6–12 months after successful eradication and cannot distinguish active infection from past exposure. 1, 3

When Endoscopy Is Required Instead

Certain high-risk conditions mandate endoscopic confirmation with biopsy-based testing:

• Gastric ulcer patients: Require endoscopic follow-up to ensure complete ulcer healing in addition to confirming H. pylori eradication 1, 2
• Gastric MALT lymphoma: Requires upper endoscopy with biopsy, as persistent infection is a negative prognostic marker for treatment failure 1, 2
• Complicated peptic ulcer disease: May require endoscopic confirmation 1

Common Pitfalls to Avoid

• Testing too early: Results obtained before 4 weeks are unreliable and may misclassify treatment failure as success 1, 2
• Inadequate medication washout: Failure to stop PPIs for 2 weeks or antibiotics/bismuth for 4 weeks will yield false-negative results 1, 2
• Using serology: Cannot distinguish active infection from past exposure 1
• Skipping test of cure: The American College of Gastroenterology states that confirmation of eradication is now the standard of care, as persistent infection predicts ulcer recurrence and complications 1

Management Based on Results

If eradication is confirmed (negative test):

• No further H. pylori testing is needed unless symptoms recur 1
• Discontinue PPI therapy in uncomplicated duodenal ulcer cases 1

If H. pylori persists (positive test):

• Use a completely different antibiotic regimen, avoiding previously failed antibiotics 1, 4
• After two treatment failures, pursue antibiotic susceptibility testing to guide third-line therapy 1, 4
• Consider testing household members for intrafamilial transmission 4