Helicobacter pylori (H. pylori) is a bacterium that infects the stomach lining and is a common cause of peptic ulcers. It affects approximately half of the world’s population and is particularly prevalent in developing countries. While many individuals with H. pylori infection remain asymptomatic, the bacterium can cause significant gastrointestinal issues, including gastritis, peptic ulcers, and in rare cases, gastric cancer [1-5].
Pathophysiology of Helicobacter pylori Infection
Colonization and Survival in the Gastric Environment
- Urease Production: H. pylori produces urease, an enzyme that hydrolyzes urea into ammonia and carbon dioxide. Ammonia neutralizes gastric acid around the bacterium, creating a more hospitable microenvironment.
- Flagella: The bacterium is motile, with flagella that help it navigate through the mucous layer of the stomach to attach to the epithelial cells.
- Adhesion: H. pylori adheres to gastric epithelial cells using various adhesins, which helps it to establish infection and evade clearance by gastric motility [1-5].
Immune Evasion and Inflammation
- Immune Evasion: H. pylori has several mechanisms to evade the host immune response, including altering its surface antigens and inhibiting immune cell function.
- Inflammatory Response: The infection triggers an immune response, leading to chronic gastritis. The bacterium’s components, such as lipopolysaccharides and peptidoglycans, stimulate the production of pro-inflammatory cytokines, contributing to mucosal inflammation and damage [1-3].
- Peptic Ulcer Disease: The combination of direct epithelial damage by the bacterium and the host inflammatory response can lead to peptic ulcers. H. pylori infection disrupts the balance between mucosal protective factors and aggressive factors like gastric acid, leading to ulcer formation.
- Gastric Cancer: Chronic inflammation induced by H. pylori can lead to atrophic gastritis, intestinal metaplasia, and eventually gastric adenocarcinoma. The bacterium’s virulence factors, such as CagA and VacA, play roles in carcinogenesis by inducing cellular proliferation, inhibition of apoptosis, and genetic instability [4,5].
Genetic Factors and Strain Variability
- Cag Pathogenicity Island (PAI): Strains of H. pylori with the cag PAI, which encodes a type IV secretion system, are associated with more severe disease, including gastric cancer.
- VacA Toxin: The VacA toxin induces vacuolation in gastric epithelial cells and can modulate immune responses, contributing to chronic infection and damage [4,5].
Transmission and Epidemiology
H. pylori is primarily transmitted via oral-oral or fecal-oral routes, often in childhood. Risk factors include crowded living conditions, lack of clean water, and poor sanitation. The prevalence of H. pylori infection varies widely by geographic region, age, and socioeconomic status [1-3].
Most individuals infected with H. pylori are asymptomatic. When symptoms do occur, they may include:
- Epigastric pain or discomfort
- Early satiety
- Peptic ulcers, presenting as more intense stomach pain, often on an empty stomach [1-3].
H. pylori infection is diagnosed using several methods:
- Non-invasive tests: Urea breath test, stool antigen test, and serology (though serology is less preferred due to its inability to distinguish between past and current infections).
- Invasive tests: Endoscopy with biopsy for histology, culture, or rapid urease testing, especially in cases of peptic ulcer disease or gastric cancer [3-5].
The goal of treatment is to eradicate H. pylori, reduce the risk of gastric cancer, and heal peptic ulcers. Treatment regimens include:
- Standard triple therapy consists of a proton pump inhibitor (PPI), clarithromycin, and either amoxicillin or metronidazole for 14 days. This regimen is effective but its efficacy has been declining due to increasing antibiotic resistance, especially to clarithromycin [4,5].
- Bismuth quadruple therapy includes a PPI, bismuth subsalicylate, metronidazole, and tetracycline for 10-14 days. This regimen is often used when there is a high rate of clarithromycin resistance or if the patient has a penicillin allergy.
- Non-bismuth quadruple therapy (sequential or concomitant) involves a PPI and three antibiotics (usually amoxicillin, clarithromycin, and metronidazole or tinidazole) taken either sequentially or concurrently [4,5].
- Based on antibiotic susceptibility testing, particularly in regions with high antibiotic resistance or in cases of treatment failure.
Follow-Up and Management of Treatment Failure
- Eradication of H. pylori should be confirmed with a urea breath test or stool antigen test, ideally four weeks after completing therapy and after stopping PPIs for at least one week.
- In cases of treatment failure, a different regimen, typically a quadruple therapy if triple therapy was used first, is recommended [4,5].
Complications and Long-Term Effects
Untreated H. pylori infection can lead to chronic gastritis, peptic ulcer disease, and is a risk factor for gastric cancer. Regular monitoring and follow-up are crucial for patients with a history of these complications [2,3].
H. pylori infection is a significant global health concern. Effective management requires accurate diagnosis, appropriate antibiotic selection, patient adherence to treatment, and follow-up testing to confirm eradication.
- Mayo Clinic. H. pylori infection [Internet]. Mayo Clinic. [cited 2023 Nov 20]. Available from: https://www.mayoclinic.org/diseases-conditions/h-pylori/symptoms-causes/syc-20356171
- Johns Hopkins Medicine. Helicobacter pylori (H. pylori) [Internet]. Johns Hopkins Medicine. [cited 2023 Nov 20]. Available from: https://www.hopkinsmedicine.org/health/conditions-and-diseases/helicobacter-pylori
- MedlinePlus. Helicobacter pylori Infections [Internet]. MedlinePlus. [cited 2023 Nov 20]. Available from: https://medlineplus.gov/helicobacterpyloriinfections.html
- UpToDate. Patient education: Helicobacter pylori infection and treatment (Beyond the Basics) [Internet]. UpToDate. [cited 2023 Nov 20]. Available from: https://www.uptodate.com/contents/helicobacter-pylori-infection-and-treatment-beyond-the-basics/print
- WebMD. Helicobacter pylori (H. pylori) [Internet]. WebMD. [cited 2023 Nov 20]. Available from: https://www.webmd.com/digestive-disorders/h-pylori-helicobacter-pylori