Helicobacter Pylori Infection, Complications and Treatment

Helicobacter Pylori Infection

It is now established that 90% of duodenal ulcers and 75% of gastric ulcers are associated with H. pylori infection. Warren and Marshall were the first to identify and isolate the organism, originally referred to as Campylobacter pyloridis.

The organism is a spiral or helical gram-negative rod with 4 to 6 flagella and resides in gastric-type epithelium within or beneath the mucus layer, which protects it from both acid and antibiotics. Its shape and flagella aid its movement through the mucus layer, and it produces a variety of enzymes that help it adapt to a hostile environment.

• Most notably, it is one of the most potent producers of urease among any bacteria yet described.
• This enzyme is capable of splitting urea into ammonia and bicarbonate, creating an alkaline environment in the setting of an acidic gastric milieu, which facilitates establishing a diagnosis of this organism by various laboratory tests.
• The organism is microaerophilic, and the optimal temperature for isolation is 35 to 37°C, with growth occurring after 2 to 5 days.
• Interestingly, H. pylori can only live in gastric epithelium because only gastric epithelium expresses specific adherence receptors in vivo that can be recognized by the organism. Thus, it can also be found in heterotopic gastric mucosa in proximal oesophagus and Barrett’s oesophagus, in gastric metaplasia in the duodenum and Meckel’s diverticulum, and in heterotopic gastric mucosa in the rectum.

The mechanism responsible for H. pylori-induced GI injury are not very clear but three potential mechanisms have been proposed:

1. Production of toxic products to cause local tissue injury
2. Induction of a local mucosal immune response
3. Increased gastrin levels with a resultant increase in acid secretion.

Locally Produced Toxic Mediators

1. Urease activity, i.e. ammonia
2. Cytotoxins
3. Mucinase that degrades mucus and glycoproteins.
4. Phospholipases that damage epithelial cells and mucus cells.
5. Platelet-activating factor, which is known to cause mucosal injury.

Mediators of Helicobacter Pylori-induced Injury

• Most H. pylori strains express—vacuolating cytotoxin.
• The VacA exotoxin causes the release of cytochrome c from mitochondria and induces apoptosis.
• H. pylori infection is accompanied by an abnormal T cell response which may be partially responsible for the long-term persistence of H. pylori infection.

Diagnosis: H. pylori infection can be diagnosed by both noninvasive and invasive means.

1. Diagnosis Non-Invasive Methods
   • They are urea breath test, serology, and detection of antigen in stool samples.
   • The urea breath test is based on production of urease by H. pylori in the gastric mucosa.
   • ¹⁴C-labelled urea is ingested and ¹⁴C-labelled CO₂ is produced and excreted in the breath.
   • This test has a sensitivity and specificity of greater than 90% and indicates ongoing infection.
   • The urea breath test is useful for initial diagnosis of infection and for follow-up after eradication therapy.
2. Diagnosis Invasive Methods
   • The patient should undergo endoscopic diagnosis and it is indicated in following situations.
     • Individuals more than 50 years of age
     • Those with significant symptoms including gastrointestinal bleeding
     • Anaemia
     • Weight loss.
   • During endoscopy, antral biopsies can be obtained and the organism cultured in agar containing both urea and a pH-sensitive colorimetric agent.
   • H. pylori hydrolysis of urea causes a diagnostic change in colour.
   • The sensitivity of this test varies from 80 to 100% and specificity exceeds 90%.
   • Biopsy also permits histologic examination with visualisation of the organism.

Culture of H. pylori is not routine and is usually reserved for recurrent infection and for antibiotic sensitivity testing when second-line therapy has failed.

Mechanism of Helicobacter Pylori-induced Injury—Summary

• Helical gram-negative rod
• Enzyme produced is urease, which splits urea. Resulting bicarbonate creates alkaline environment. Another enzyme mucinase degrades mucus.
• Lives only in gastric epithelium
• Injury is due to:
  • Toxins such as vacuolating cytotoxin
  • Increased gastrin levels
  • Phospholipases
  • Platelet-activating factor
  • Increased immunoglobulin response (host response)
• Cytotoxins
• Other factors
  • Local tissue injury
  • Local ischaemia

Remember as HELICO

Helicobacter Pylori Infection Treatment

• To be effective, antimicrobial drugs must be combined with gastric acid secretion inhibitors or bismuth salts.
• Cure rates of 80-85% are achieved using combination therapy, usually proton pump inhibitors, ranitidine, or bismuth citrate with two antibiotics.
• The most common antibiotics used are clarithromycin, amoxicillin, and metronidazole or tinidazole.
• Metronidazole has been a mainstay of H. pylori treatment.
• Eradication therapy with a proton pump inhibitor, metronidazole, and amoxicillin decreases the pre-valence of metronidazole-resistant H. pylori strains.

Helicobacter Pylori Infection Different Regimens

• Bismuth triple therapy: Bismuth, 2 tablets four times daily + Metronidazole, 250 mg three times daily + Tetracycline, 500 mg four times daily.
• PPI triple therapy: PPI twice daily + Amoxicillin, 1000 mg two times daily + Clarithromycin, 500 mg two times daily or metronida¬zole, 500 mg two times daily.
• Quadruple therapy: PPI twice daily + Bismuth, 2 tablets four times daily + Metronidazole, 250 mg three times daily + Tetracycline, 500 mg four times daily.

Complications of Helicobacter Pylori Infection

1. Chronic duodenal ulcer
2. Gastric carcinoma
3. Gastro-oesophageal reflux disease
4. Barrett’s oesophagus
5. Chronic gastritis
6. Gastric maltoma
7. Oesophageal cancer
8. Idiopathic thrombocytopenic purpura.