Helicobacter pylori

Epidemiology

Estimated half of world's population effected
Prevalence in peptic ulcers of 50-75%
Spontaneous remission is rare
Most patients with gastric cancer have current or past infection
Rare in children (5% in Australia) and almost always asymptomatic

Pathophysiology

Spiral-shaped, flagellate, gram-negative bacteria
Resides in gastric-type epithelium within or beneath the mucus layer
- Heterotopic gastric mucosa in proximal oesophagus
- Barrett oesophagus
- Gastric metaplasia in the duodenum
- Within a Meckel diverticulum
- Heterotopic gastric mucosa in the rectum
Adaptations:
- Mucolytic enzymes including protease - protect from mucus
- Urease - creates an alkaline microenvironment
- Propulsion by flagella
- Attachment to epithelium - receptor-mediated adhesion
- Catalase - allows the organism to survive host defence inflammation
Proposed mechanisms of injury:
- Production of toxic products that cause local tissue injury
  - Not present in all strains, but when they are present, more likely to cause injury:
    - CagA - cytotoxin-associated gene A - necessary for VacA expression - disrupts cell integrity
    - VacA - vacuolating cytotoxin - stimulates apoptosis of cells
  - Several others
- Induction of a local mucosal immune response - which is the mechanism by which most damage is caused
  - Produces antigenic substances such as lipopolysaccharides
  - Lead to increased local IL-1, IL-6 and TNF-alpha
- Alterations to gastrin levels and changes in acid secretion
  - See below
  - Acid can be increased or decreased during the acute phase (depending on whether there is antral-predominant disease or pan-gastritis respectively) and decreased during the chronic phase
- Gastric metaplasia in the duodenum
  - Likely occurs as a protective response to decreased duodenal pH
  - Allows H. pylori to colonise the duodenum
Pattern of injury
- Almost all infected patients have antral gastritis, as opposed to NSAID ulcers, of which only 25% have antral gastritis
- Infection tends to be confined initially to the antrum
- Ulcers frequently found in the duodenum/antrum
- >90% of duodenal ulcers are associated with H pylori; 60% of gastric ulcers

Clinical features

Most infected patients are asymptomatic
See 'PUD' page

Gastric atrophy from long-standing H. pylori

Invasive tests

Urease assay/Rapid urease test/CLO test
- Use four endoscopic biopsy specimens from gastric body and antrum
- Test specimens for urease. If Helicobacter is present, urease will hydrolyse the urea in the sample well to ammonium, causing a rise in pH and thus a colour change. Any red/pink/orange is positive, while yellow is negative. Technically needs 24 hours to fully react.
- Sensitivity >90%, specificity 95-100%
- Lower sensitivity in those taking PPIs, H2 antagonists, or antibiotics - only worthwhile doing when it will change management, i.e. you have a high enough suspicion that you want to start treating right away instead of waiting for histology
Histology
- Biopsy from both antrum and body - the organisms tend to migrate proximally with PPI use
- Histologic visualisation of H. pylori using either routine haematoxylin-eosin stains or other special stains
- Sensitivity 95%, specificity 99%
- Lower sensitivity in those taking PPIs, H2 antagonists, or antibiotics
- More expensive than urease assay
Culture
- Biopsy specimens obtained at endoscopy
- Need to take specimen before forceps are contaminated with formalin
- Sensitivity 80%, specificity 100%
- Takes 3-5 days
- Can do sensitivities

Non-invasive tests

Urea breath test
- Ingest a tablet containing urea with a labelled carbon isotope, which will be broken down by urease. The proportion of labelled CO2 in an exhaled breath can be used to determine the presence of urease.
- Sensitivity and specificity >95%
- Lower sensitivity in those taking PPIs, H2 antagonists, or antibiotics
  - Cease antibiotics for 4/52 and PPI for 2/52
- Wait 4/52 after treatment
- Can be done while acutely unwell with bleeding or perforation
Stool antigen
- Monoclonal antibodies that H. pylori antigens to test for H. pylori in faecal specimens
- Works since H. pylori bacteria will be present in the stool of infected patients
- Sensitivity >90%, specificities 86-92%
- Accurate for testing eradication
- Non-specific with blood present
Serology
- 90% sensitivity, 76-96% specificity
- Antibody titres can remain high for up to 1 year after eradication; not useful for confirming eradication

Eradication therapy

First-line: HP7 for 14 days
- Esomeprazole 20mg orally bd
- Amoxicillin 1g orally bd
- Clarithromycin 500mg orally bd
Allergic to penicillins: for 14 days
- PPI BD
- Metronidazole 400mg BD
- Clarithromycin 500mg BD
Second-line
- Quinolone therapy (10 days) - efficacy >85% - preferred second-line in Australia
  - PPI BD
  - Amoxicillin 1g BD
  - Levofloxacin 250mg BD or moxifloxacin 400mg BD
- Bismuth (7-14 days)
  - PPI BD
  - Colloidal bismuth subcitrate 120mg QID on an empty stomach
  - Tetracycline 500mg QID on an empty stomach
  - Metronidazole 400mg TDS with food
Third-line
- Rifabutin-based triple therapy
  - PPI BD
  - Amoxicillin 1g BD
  - Rifabutin 150mg BD
Basically, amoxicillin and PPI are always given, but the other drug is clarithromycin -> moxifloxacin -> rifabutin
If allergic to penicillin, just swap out the amoxicillin for metronidazole

Monitoring for eradication

~20% of patients fail first-line therapy - likely due to resistance
Need to do urea breath test, stool antigen or repeat scope at 4-6 weeks (urea breath test is best)

Repeat gastroscopy for H. pylori-confirmed ulcers if:

Persistent symptoms after discontinuation PPI
Giant gastric ulcer (>2cm)
Ulcer with features of malignancy at index operation
Gastric ulcer that wasn't biopsied in all 4 quadrants at index endoscopy
Risk factors for gastric cancer

Complications

MALT lymphoma
- Strong association between MALT lymphoma and H. pylori
- Eradication of H. pylori leads to regression