Helicobacter pylori and the pathogenesis of duodenal ulcer.

In summary, it appears that the role of H. pylori in duodenal ulcerogenesis is not directly associated with acid hypersecretion. Similarly, it seems unlikely that H. pylori-induced autoimmune injury is an important mechanism in duodenal ulcerogenesis. An essential question remaining is whether H. pylori infection of areas of gastric metaplasia in the duodenum is essential to ulcer pathogenesis. The low yield of H. pylori in duodenal biopsy studies argues against this mechanism. It is possible that H. pylori gastritis (present in greater than 90% of duodenal ulcer patients) results in the release of inflammatory mediators into the gastric lumen that wash down to the duodenum with gastric emptying. Such a mechanism would explain both the low recovery rate of H. pylori from duodenal biopsies in ulcer patients and the local IgA response seen in the first part of the duodenum in response to H. pylori antigens. This could also explain the high incidence of H. pylori gastritis in patients with duodenal ulcers. Obviously the four theories discussed in this review are not mutually exclusive. Significant interaction may occur between the mechanisms described. In addition, bacterial strain differences may be more important than variations in host response to H. pylori infection. Genetic studies focused on strain differences regarding mediator production and release will help clarify these issues. In the vast majority of patients with duodenal ulcer, H. pylori infection appears to be required but is not sufficient for pathogenesis of the disease. The mechanisms of ulcerogenesis related to H. pylori remain incompletely understood. Several recently identified animal models including the gnotobiotic piglet and the naturally occurring H. mustelae infection in ferrets hold substantial promise for solving the puzzle of H. pylori disease.