Helicobacter pylori is a spiral bacterium that colonises the gastric mucosa, and the interaction between its virulence factors and the host response decides the outcome of the infection.
Epidemiology
Several risk factors for H. pylori infection are recognised: birth or residence in a developing country, domestic crowding, unsanitary living conditions, unclean food or water, and exposure to the gastric content of an infected person. Transmission is through oral–oral or fecal–oral pathways.
In developing countries, the prevalence of H. pylori infection by age 20 is about 80%, whereas in developed countries it is about 20–50%. The overall prevalence in the United States is about 30%. Fortunately, during the last 30 years the incidence of H. pylori infection has been reducing in both developing and developed countries.
Bacterial and host factors
The interplay between bacterial factors and host factors in H. pylori infection plays an important role in the final result of the infection, its complications and its eradication.
Among the bacterial factors, flagella, urease and GGT help the organism colonise and survive in the stomach. CagA marks the strains associated with a higher risk of peptic ulcer disease and of pre-malignant and malignant conditions; CagA-positive strains can also directly inhibit the parietal cells, leading to low acid production in acute infection. VacA affects the normal function of CD4+ and CD8+ T cells, macrophages and B cells. Phospholipases and proteases disrupt the mucosal barrier of the stomach, and a bacterial surface chemoattractant attracts monocytes, causing cell injury. The LPS of H. pylori is, in comparison with other bacteria, not very immunogenic.
Among the host factors, studies in twins suggest that there may be a genetic predisposition to H. pylori, and the microbial composition of the stomach seems to affect the final effect and pathogenicity of the infection.
Mechanisms of epithelial injury
Epithelial cell injury of the gastric epithelium in H. pylori infection happens through several routes. Direct contact of H. pylori with epithelial cells through MHC-II leads to apoptosis, and the recruitment of inflammatory cells such as macrophages, T and B cells causes further cell death: neutrophils form ROS, and cytokines such as IFN mediate cell death. CagA-positive H. pylori induces more cytokine production and inhibits the expression of tumour-repressor proteins. Bacterial virulence factors such as urease also lead to the formation of NO, and the resulting radicals damage cells.
Duodenal ulceration
The pathogenesis of duodenal ulceration due to H. pylori is still not completely established, but there are several hypotheses. More virulent bacteria may cause duodenal ulcer; strains with the duodenal ulcer-promoting gene A (dupA), for instance, cause it more often. Gastric metaplasia of the duodenum makes it possible for H. pylori to attach to the duodenum and cause ulcer. And antral infection by H. pylori increases acid production and so favours duodenal ulcer.
When acid production is increased in H. pylori infection, as in duodenal ulcer, this is hypothesised to happen in three ways: by acting directly on G cells to produce more gastrin; indirectly, through inflammatory cytokines that act on G cells to produce more gastrin; and indirectly, by affecting D cells, leading to higher production of acid.
Gastric ulceration
Gastric ulcer due to H. pylori is mostly related to pan-gastritis. Because of atrophy and pan-gastritis, acid production in H. pylori-caused gastric ulcer is lower or normal.
In the first studies, more than 90% of duodenal ulcers were related to H. pylori infection. Nowadays we know that 30–60% of gastric ulcers and 50–70% of duodenal ulcers are due to H. pylori infection.