H. pylori Infection

Overview.

Helicobacter pylori is a gram-negative bacterium that colonizes the gastric mucosa and infects approximately 44% of the global population. It is the leading cause of peptic ulcer disease and gastric adenocarcinoma — classified as a Group 1 carcinogen by the WHO. Despite its prevalence, the majority of infected individuals are asymptomatic and unaware of their infection. The key diagnostic principle: serology detects exposure but cannot confirm active infection — only a urea breath test or stool antigen test can do that.

H. pylori uses the enzyme urease to neutralize stomach acid, creating a survivable microenvironment in the gastric mucosa. Key virulence factors — particularly CagA protein injected via a Type IV secretion system — drive chronic gastric inflammation in virtually all infected individuals. Over decades, this can progress through a cascade (Correa pathway): chronic gastritis → gastric atrophy → intestinal metaplasia → dysplasia → gastric adenocarcinoma. However, most infected individuals never progress to cancer, with individual risk shaped by bacterial strain, host genetics, and environmental co-factors.

Prevalence: Infects approximately 44% of the global population — roughly 3.5 billion people. Prevalence ranges from 20-30% in high-income countries (North America, Western Europe, Australia) to 70-80% in low- and middle-income countries. Infection is predominantly acquired in childhood through fecal-oral or oral-oral transmission and persists lifelong without treatment.

Medical name: Helicobacter pylori Infection

Symptoms.

Early warnings

• Recurring upper abdominal (epigastric) pain or burning
• Pain that improves temporarily with eating or antacids
• Unexplained iron deficiency anemia (H. pylori can cause occult GI bleeding)
• Persistent nausea or early satiety
• Frequent burping

Classic symptoms

• Epigastric pain — typically burning or gnawing, may radiate to back
• Peptic ulcer symptoms: duodenal ulcer pain improves with eating; gastric ulcer pain may worsen with eating
• Nausea, occasional vomiting
• Loss of appetite and unintentional weight loss (in active ulcer disease)
• Hematemesis or melena (black stools) in bleeding ulcer — seek urgent care

Progression

The majority of H. pylori-infected individuals (~85%) remain asymptomatic. Of those who develop complications: ~15-20% develop peptic ulcer disease, ~1-3% develop gastric cancer over a lifetime, <0.1% develop MALT lymphoma. H. pylori eradication reduces gastric cancer risk by approximately 35-45% (RR 0.56; PMID: 28655977) [Systematic Review] and heals peptic ulcers with very low recurrence rates after successful eradication.

Risk factors.

• Childhood exposure in household with infected family members
• Low socioeconomic status and crowded living conditions
• Living in or emigrating from high-prevalence regions
• Lack of access to clean water and sanitation
• Prior peptic ulcer disease (most peptic ulcers are H. pylori-related)
• Family history of gastric cancer (first-degree relative)
• Regular NSAID or aspirin use (cofactor for ulcer risk)

Lab interpretation.

Key biomarkers

• H. pylori IgG Serology — Positive in active infection AND past infection; cannot distinguish the two; remains positive 12+ months after eradication (screening-only)
• Ferritin / Iron Studies — Low in H. pylori-associated refractory iron deficiency anemia; mechanism: occult bleeding + impaired iron absorption from altered gastric pH (secondary)
• CBC (Complete Blood Count) — Microcytic anemia from iron deficiency or blood loss in peptic ulcer disease (secondary)
• Fasting Gastrin — Elevated in H. pylori gastritis (antral predominant) and with PPI use; markedly elevated in Zollinger-Ellison syndrome (rule out if >1000 pg/mL) (secondary)

Diagnostic criteria

• Urea breath test (UBT) or stool antigen test (SAT) are preferred first-line tests for initial diagnosis and test-of-cure
• Serology (IgG) is NOT suitable for confirming active infection or test-of-cure — remains positive after eradication
• If upper endoscopy is performed: rapid urease test (RUT) and histopathology are the preferred endoscopy-based tests
• Stop PPIs at least 2 weeks before UBT, SAT, or RUT to reduce false-negative rates
• Stop antibiotics at least 4 weeks before testing
• Test-of-cure (UBT or SAT) is mandatory at least 4 weeks after completing eradication therapy

Recommended panels

• Upper Gi Panel
• Iron Panel
• Cbc

When & next steps.

When to test

• Active or prior peptic ulcer disease (gastric or duodenal)
• Unexplained iron deficiency anemia, especially refractory to oral iron
• Low-grade gastric MALT lymphoma
• Prior endoscopic resection of early gastric cancer
• First-degree relative with gastric cancer
• Functional dyspepsia (test-and-treat strategy; NNT ~14 for symptom benefit)
• Before starting long-term NSAID or antiplatelet therapy
• Chronic unexplained nausea or epigastric discomfort
• Screening in high-prevalence regions or high-risk populations

If suspected

• Order urea breath test (UBT) — preferred non-invasive active infection test; or stool antigen test (SAT) if UBT unavailable
• If upper endoscopy is planned for other reasons: request rapid urease test (RUT) and biopsies for histopathology
• Check CBC and iron/ferritin if symptoms of anemia
• Do NOT use serology alone to diagnose active infection or guide treatment decisions
• Stop PPIs 2 weeks before testing, antibiotics 4 weeks before testing, to prevent false negatives

If confirmed

• Bismuth quadruple therapy (BQT) for 14 days is the preferred first-line regimen per ACG 2024 guideline (Chey WD et al., PMID: 39626064)
• Clarithromycin-based triple therapy is no longer first-line due to rising antibiotic resistance (>15% in most regions)
• Mandatory test-of-cure: UBT or SAT at least 4 weeks after completing therapy AND at least 2 weeks off PPI
• If first-line therapy fails: treat with optimized bismuth quadruple therapy; susceptibility testing guides salvage regimens
• After confirmed eradication in peptic ulcer disease: repeat endoscopy at 4-8 weeks for gastric ulcers to confirm healing and rule out malignancy

FAQs.

Important note.