Helicobacter pylori

Over the last 20 years this organism has proved to be of overwhelming importance in the aetiology of a number of common gastroduodenal diseases such as chronic gastritis, peptic ulceration and gastric cancer. The organism had unquestionably been observed by a number of workers since Bircher’s first description in 1874, but it was not until 1980 that Warren and Marshall, with enthusiasm but perhaps a lack of caution, ingested the organism to confirm that Koch’s postulates could be fulfilled with respect to the gastritis that they succeeded in causing in themselves. Eradication therapy was then employed with mixed success. The organism is spiral shaped and is fastidious in its requirements, being difficult to culture outside the mucous layer of the stomach.

One of the characteristics of the organism is its ability to hydrolyse urea, resulting in the production of ammonia, a strong alkali. The effect of ammonia on the antral G cells is to cause the release of gastrin via the previously described negative-feedback loop. This is probably responsible for the modest but inappropriate hypergastrinaemia in patients with peptic ulcer disease which, in turn, may result in gastric acid hypersecretion. The organism’s obligate urease activity is utilised by various tests used to detect the presence of the organism, including the C13 and C14 breath tests and the CLO test (which is a commercially available urease test kit), which is performed on gastric biopsies. The organism can also be detected histologically (Fig. 51.13), using the Giemsa or the Ethin—Stary silver stains, and cultured using appro­priate media. Previous or current infection with the organism may also be detected serologically.

Infection leads to the disruption of the gastric mucous barrier by the enzymes produced by the organism, and the inflammation induced in the gastric epithelium is the basis of many of the associated disease processes. The association of the organism with chronic (type B) gastritis is not in doubt as Koch’s postulates have been fulfilled, most notably by Marshall and Warren. Some strains of H. pylori produce cytotoxins, and the production of cytotoxin seem to be associated with the ability of the organism to cause both gastritis and peptic ulceration (Crabtree). The effect of the organism on the gastric epithelium is to incite a classical inflammatory response that involves the migration and degranulation of acute inflammatory cells, such as neutrophils, and also the accumulation of chronic inflammatory cells, such as macrophages and lymphocytes.

It is evident how H. pylori infection results in chronic gastritis and also how this may progress to gastric ulceration, but it remained for a while an enigma how the organism could be involved in duodenal ulceration as the normal duodenum is not colonised. As mentioned above, the pro­duction of ammonia does increase the level of circulating gastrin and it has subsequently been shown that eradication of the organism in patients with duodenal ulcer disease will reduce the acid levels to normal. However, the overlap in gastric acid secretion between normal subjects and those with duodenal ulcers is considerable and the modestly increased acid levels in patients with Helicobacter-associated antral gastritis are insufficient to explain the aetiology of duodenal ulceration.

The explanation can probably be found in the phenom­enon of duodenal gastric metaplasia. Gastric metaplasia is the normal response of the duodenal mucosa to excess acidity. It can be thought of as any other metaplasia in the gastroin­testinal tract: an attempt by the mucosa to resist an injurious stimulus. Although normal duodenal mucosa cannot be infected with H. pylori gastric metaplasia in the duodenum is commonly infected and this infection results in the same inflammatory process that is observed in the gastric mucosa (Wyatt and Dixon). The result is duodenitis, which is almost certainly the precursor of duodenal ulceration.

Infection with H. pylori may be the most common human infection. The incidence of infection within a population increases with age, and in many populations infection rates of 8 0—90 per cent are not unusual. The possibility of infection is inversely related to socioeconomic group. The means of spread has not been identified, but the organism can occur in the faeces and faecal—oral spread seems most likely. The organism is not normally found in saliva or dental plaque. There is evidence in different environments and in different population groups that the manifestations of the infection may be different. Predominantly antral gastritis, which is commonly seen in the West, results initially in increased levels of acid production and peptic ulcer disease whereas gastritis affecting the body, common in the developing world, may lead to hypochlordria and gastric neoplasia.

It has been known since 1984 that Helicobacter infection is amenable to treatment with antibiotics and, in addition, that bismuth compounds are toxic for the organism. The profound hypochlorhydria produced by proton pump inhibitors combined with antibiotics is also effective in eradi­cating the organism. Commonly used eradication regimes include a bismuth compound and two antibiotics, such as metronidazole and amoxycillin, or a proton pump inhibitor, such as omeprazole, again in combination with antibiotics. High eradication rates in the region of 90 per cent can be achieved with combinations which include the antibiotic clarithromycin, although it may be that in the future antibiotic resistance becomes a problem.

At present eradication therapy is recommended for patients with duodenal ulcer disease but not for patients with non ulcer dyspepsia or in asymptomatic patients who are infected. However, recent data show that a proportion of patients with nonulcer dyspepsia does respond to treatment. Helicobacten pylori is now classed by the World Health Organisation as a class 1 carcinogen and it may be that the further epidemiological studies on the risk of gastric cancer change the current advice on treatment.