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.