Helicobacter pylori infection

"SMART" Bacterial Features

• S: Spiral-shaped for easy penetration of the gastric mucous layer.
• M: Microaerophilic; thrives in low oxygen environments.
• A: Adhesion molecules facilitate attachment to gastric epithelial cells.
• R: Resistant to acidic pH due to urease production.
• T: Toxin-producing (CagA and VacA) leading to mucosal damage.

Survival Mechanisms

• Urease Production:
  
  • Converts urea into ammonia and CO₂.
  • Creates an alkaline microenvironment, neutralizing gastric acid.
  • Basis for urease-based diagnostic tests (e.g., urea breath test).
• Flagella:
  • Multiple flagella enhance motility.
  • Allows navigation through the mucous layer to colonize epithelial cells.
• Adhesion Molecules:
  • Help in firm attachment to the gastric epithelium.
  • Prevents clearance by peristalsis.

Gender Distribution

• Children: Male = Female.
• Adults: Males > Females.

Transmission Routes

• Primary: Fecal-oral route.
• Others:
  • Contaminated water.
  • Person-to-person (especially within families).
  • Possibly oral-oral via saliva.

Risk Factors

• "CLOSE" Contacts:
  • C: Crowded living conditions.
  • L: Low socioeconomic status.
  • O: Overcrowding.
  • S: Sanitation poor.
  • E: Exposure within families.

Disease Development Cascade

1. Initial Colonization:
   • Bacteria penetrate the mucous layer using flagella.
2. Inflammation Initiation:
   • Urease activity and toxins provoke an immune response.
   • Neutrophils and lymphocytes infiltrate the mucosa.
3. Chronic Gastritis:
   • Persistent inflammation damages the gastric mucosa.
4. Disease Progression:
   • PUD: Ulceration due to erosion of the mucosal lining.
   • Atrophic Changes: Loss of gastric glandular cells.
   • Intestinal Metaplasia: Replacement with intestinal-type epithelium.
   • Dysplasia and Cancer: Increased risk of gastric adenocarcinoma.
   • MALT Lymphoma: Proliferation of lymphoid tissue.

Toxin Effects

• CagA (Cytotoxin-associated gene A):
  • Alters cell signaling pathways.
  • Associated with increased cancer risk.
• VacA (Vacuolating cytotoxin A):
• Induces cell vacuolation and apoptosis.
• Disrupts mitochondrial function.

Disease Spectrum

Symptoms

• Dyspepsia:
  • Upper abdominal discomfort.
  • Bloating, nausea, and early satiety.
• Peptic Ulcer Disease:
  • Gastric Ulcers:
    • Pain worsens with meals.
    • Weight loss common.
    • Location: Lesser curvature, incisura angularis.
    • Biopsy necessary due to malignancy risk (~4%).
  • Duodenal Ulcers:
    • Pain relieved by meals but worse 2–3 hours postprandially.
    • Nocturnal pain is common.
    • Weight gain may occur.
    • Location: First part of duodenum.
    • Biopsy not routinely needed.

Detailed Ulcer Comparison

Important Pre-Test Considerations

• Medication Interference:
  • Proton Pump Inhibitors (PPIs):
    • Hold for 1–2 weeks before testing to avoid false negatives.
  • Antibiotics and Bismuth Compounds:
    • Hold for ≥4 weeks before testing.
• Exception: Histology testing is not significantly affected by recent PPI use.

When to Test

• Gastrointestinal Conditions
  • Active PUD or history of PUD without documented eradication.
  • Uninvestigated dyspepsia.
  • Early gastric malignancy (e.g., MALT lymphoma).
  • Functional dyspepsia.
• Other Indications
  • Before initiating long-term low-dose aspirin or NSAIDs.
  • Unexplained iron deficiency anemia.
  • Idiopathic thrombocytopenic purpura.
  • Adults sharing a household with infected individuals.
  • Individuals at high risk for gastric cancer.

Diagnostic Tests Comparison

Non-Invasive Tests

• Urea Breath Test:
  
  • Patient ingests labeled urea; detection of labeled carbon dioxide indicates presence of H. pylori.
  • Advantages: High accuracy.
  • Limitations: Affected by PPIs, antibiotics, and bismuth; patient preparation required.
• Stool Antigen Test:
  • Detects H. pylori antigens in feces.
  • Advantages: High accuracy; useful for initial diagnosis and post-treatment confirmation.
  • Limitations: Affected by medications; requires proper specimen handling.
• Serology (IgG Antibody Test):
  • Detects antibodies against H. pylori.
  • Advantages: Not affected by recent medications.
  • Limitations: Cannot distinguish active from past infection; not recommended for eradication confirmation.

Invasive Tests (during Endoscopy)

• Rapid Urease Test:
  • Biopsy specimen tested for urease activity.
  • Advantages: Quick results; high specificity.
  • Limitations: Affected by medications; requires endoscopy.
• Histology:
  • Gold Standard: Microscopic examination of stained biopsy tissue.
  • Advantages: Can detect gastritis, metaplasia, dysplasia, cancer.
  • Not Affected: By recent PPI use.
• Culture and Sensitivity:
  • Allows for antibiotic susceptibility testing.
  • Limitations: Time-consuming; not routinely performed.

General Principles

• Eradication therapy is recommended for all individuals testing positive for H. pylori.
• First-line therapy is the Optimized Bismuth Quadruple Therapy due to rising antibiotic resistance.
• Antibiotic sensitivity testing should be considered in:
  • Penicillin allergy.
  • Previous macrolide or fluoroquinolone use.
  • Previous treatment failures.

First-Line Treatment

Optimized Bismuth Quadruple Therapy (Duration: 10–14 days):

• Proton Pump Inhibitor (PPI):
  • Standard dose twice daily (e.g., omeprazole 20 mg BID).
• Bismuth Subsalicylate:
  • 300 mg four times daily (QID).
• Tetracycline:
  • 500 mg four times daily (QID).
• Metronidazole:
  • 500 mg three to four times daily.

Alternative Regimens

• Rifabutin Triple Therapy (Duration: 14 days):
  
  • Rifabutin 150 mg twice daily.
  • Amoxicillin 1 gram twice daily.
  • PPI standard dose twice daily.
• Potassium-Competitive Acid Blocker (PCAB) Therapy (Duration: 14 days):
  • Vonoprazan-Based Dual Therapy:
    • Vonoprazan 20 mg twice daily.
    • Amoxicillin 1 gram three times daily (TID).
  • Vonoprazan-Based Triple Therapy:
    • Vonoprazan 20 mg twice daily.
    • Amoxicillin 1 gram twice daily.
    • Clarithromycin 500 mg twice daily.

Treatment Notes

• Bismuth Compounds:
  • Provide mucosal protection and have antimicrobial activity.
• Antibiotic Selection:
  • Avoid antibiotics previously used by the patient.
  • Clarithromycin-based therapy is less preferred due to resistance.
• Penicillin-Allergic Patients:
  • Bismuth quadruple therapy is preferred if tolerated.
  • Consider allergy testing if penicillin allergy is unconfirmed.

Confirmation of Eradication

• Indications: Recommended for all patients after therapy completion.
• Timing:
  • Testing should be performed ≥4 weeks after completion of therapy.
  • Hold PPIs for 1–2 weeks before testing to prevent false negatives.
• Preferred Tests:
  • Urea Breath Test.
  • Stool Antigen Test.
  • Endoscopic Biopsy with Rapid Urease Test (if endoscopy is indicated).
• Note: Serology is not suitable for eradication confirmation due to persistent antibodies.

Peptic Ulcer Disease (PUD)

• Gastric Ulcers:
  • Associated with pain aggravated by meals.
  • Risk of bleeding, perforation, and gastric outlet obstruction.
  • Commonly located near the incisura angularis.
  • Biopsy Recommended: Risk of malignancy (~4%).
  • Follow-Up: Healing confirmation via endoscopy is needed.
• Duodenal Ulcers:
  • Pain relieved by meals but worse 2–3 hours postprandially.
  • More common than gastric ulcers.
  • Typically located in the first part of the duodenum.
  • Biopsy Not Routinely Needed: Rarely malignant.
  • Follow-Up: Routine endoscopic confirmation not necessary unless complications arise.

Gastric Malignancies

• Gastric Adenocarcinoma:
  • Result of chronic inflammation leading to atrophic gastritis and intestinal metaplasia.
  • H. pylori classified as a Group 1 carcinogen by WHO.
• MALT Lymphoma:
  • Low-grade B-cell lymphoma from mucosa-associated lymphoid tissue.
  • May regress with H. pylori eradication therapy.

Other Complications

• Iron Deficiency Anemia:
  • May be the sole presentation.
  • Caused by chronic blood loss or impaired iron absorption.
• Vitamin B12 Deficiency:
  • Due to malabsorption from chronic gastritis.
• Gastric Atrophy and Metaplasia:
  • Long-standing inflammation leads to loss of gastric glandular cells.
  • Increases the risk for dysplasia and gastric cancer.