Editing 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
[[Category:UGIS]]