H. PYLORI INFECTION


DEFINITION
Infection of the stomach lining or irritated intestine with a small spiral shaped bacteria, which has an important role in gastritis, gastric ulcer, and gastric cancer.

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INCIDENCE

Prevalent in developing countries.
?1/3 - 2/3 of West infected, high in older population.
Increases with lower socioeconomic status.

Rare where PUD rare, eg Africa
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AETIOLOGY
Spiral gram-negative bacterium.
Probably fecal-oral transmission.
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BIOLOGICAL BEHAVIOUR

Pathophysiology

H. pylori colonizes the gastric epithelium beneath the mucus layer (in gastric pits).
Mainly in antrum or areas of gastric metaplasia.
Produces urease
- live in mucus layer, urease produces a pH-neutral internal and pericellular environment to assist survival.

Toxins
Differences in symptoms in context of high infection rate believed due to strain and vague host factors (e.g. gastrin sensitivity).
Produce acetaldehyde, toxins and mucolytic factors; activate inflammatory response in adjacent epithelium; chronic oxidative stress contributes to further cellular damage.
Type 1 H. pylori also releases cytotoxins that damage tissue (Vac A and Cag A).
Type II is negative for these.
Combination of toxins and chronic inflammatory response --> chronic atrophic gastritis
- i.e. mucosal thinning, loss of specialized glands and compensatory increase in cellular turnover in the proliferative zone.

Natural History
Only a minority of patients develop ulcers.
Acute gastritis --> chronic atrophic gastritis.
Chronic gastritis can --> metaplasia --> dysplasia --> gastric cancer.
- metaplasia is a consequence of selection pressures by modified microenvironment and pathologic effects on transcription facctors
-  shows different types, related to somatic mutations or epigenetic events in stem cells., e.g. DNA hypermethylation, p53 abnormalities
- metaplasia may be complete, incomplete; associated with absorptive instead of secretory mucosa and commonly Paneth cells (granular immune cells); and intestinal (typically) or somewhat colonic type.
- cause of progression to dysplasia is less clear; note that atrophic gastritis and even intestinal metaplasia are common in older people, so additional pathogenic factors are active.
- probably a consequence of H. pylori blocking defense (hypochlrohydria and blocked ascorbic acid section) and mutagenic DNA damage (convert nitrates to nitrite; N-nitrosating agents from nitric oxide) --> mutates p53, genetic instability.
Also more than 90% MALT tumours (mucosal-associated lymphoid tissue) shown associated with H. pylori.

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MANIFESTATIONS
As for gastritis, dyspepsia, complications of ulcer and cancer.

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INVESTIGATIONS


1. Serological tests for IgG antibodies
- easy, safe, and cheap.
- use for pts with no features of complciated ulcer and history of documented ulcer, but not yet treated for h. pylori
- however, these remain +ve after eradication, so can't use for follow-up.

2. Urea breath test (with 13C or 14C isotopes - non-radioisotope 13C if possible, but must have expensive mass spectrometer for this).
- more sensitive, specific and expensive
- better suited to defining eradication; use it 4 weeks after last dose of antimicrobials and 7 days after last PPI dose.
- however, because it is expensive, not necessary in all patients, only those with documented peptic ulcers of complicated/refractory ulcers.
- can get false -ves in pts taking antisecretory drugs or antimicrobials.

3. Stool antigen testing
- emerging; seems to have good sensitivity and specificity.
- not yet recommended for eradication proof though.

4. Endoscopy, with biopsy
- urease test of antral biopsy, or can visualize
--> culture and histology.
- rapid urease test or histologic visualization can demonstrate bacteria

5. Clinical Evaluation
Absence of symptoms on completion of H pylori therapy has been shown to be accurate for eradication of H pylori, in those who had symptoms.

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MANAGEMENT

Medical
Some treat if found, even if no symptoms, due to risks of Ca pathway.

PPI based triple therapy (e.g. omeprazole 20 mg bd AND metronidazole 500 mg bd AND clarithromycin 500 mg bd for 2/52).
- PPIs have in-vitro activity against h-pylori.
Other regimens may use a H2 receptor antagonist.

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References
Doherty
Companion Series 4th