Blaut_edit_Layout 1 05/10/2009 11:00 Page 59
Helicobacter pylori Infection in the Pathogenesis of Gastro-oesophageal Reflux Disease
lesions. GORD, peptic ulcer disease and gastritis are traditionally Helicobacter pylori Infection and
classified as the acid-related diseases. Since it is an undisputable fact Gastric Acid Secretion
that chronic Helicobacter pylori infection affects gastric acid The primary pathway by which H. pylori influences the pathogenesis
production, the question may be raised whether this condition of GORD is modification of gastric secretion and, consequently,
contributes to GORD development. oesophageal refluxate content. This effect is exerted by a few
mechanisms that eventually result in decreased or increased acid
Epidemiology secretion. The first mechanism is interruption of feedback inhibition of
In earlier epidemiological studies an increasing recognition of GOR in gastrin release due to luminal acid increase. Gastrin levels in H. pylori-
developed countries has been paralleled by a falling prevalence of infected patients are higher and do not exhibit a normal feedback
H. pylori infection.
4
This observation led several investigators to estimate relationship.
16
Hypergastrinaemia may by the primary phenomenon
the prevalence of H. pylori in patients with GORD. In 1997 Werduller at al. arising due to H. pylori-related inhibition of somatostatin production in
published a prospective study confirming that the prevalence of H. pylori antral D-cells in patients with antral-predominant gastritis. This may
infection in patients with GORD is significantly lower than in the control be also an event secondary to decreased acid secretion in patients
group.
5
This was supported by similar results obtained by other with long-standing chronic, atrophic corpus-predominant gastritis.
investigators. A large meta-analysis summarising the results of 14 case-
control studies and 10 clinical trials proved that H. pylori-negative status Independent of the pathways described above, H. pylori inhibits
was associated with a significantly increased risk of GORD (pooled odds parietal cells both directly and indirectly.
17
Direct inhibition is exerted
ratio [OR] 1.34, 95% confidence interval [CI] 1.15–1.55).
6
Similarly, a link by downregulation of gastric H
+
-K
+
-ATPase α-subunit gene
between eradication and GORD was observed in therapeutic trials. expression via intracellular pathways involving protein kinase A and C
These epidemiological data do not support a role for H. pylori in the and protein tyrosine kinase.
18
On the other hand, H. pylori infection
pathogenesis of reflux disease, but rather suggest a negative association leads to production of pro-inflammatory cytokines such as
with the increasing incidence of oesophageal diseases. interleukin-8 (IL-8), IL-1α and tumour necrosis factor-α (TNF-α). The
inflammatory process may damage epithelial cells, including parietal
Another point of concern was the relationship between severity of cells. However, cytokines also inhibit acid secretion functionally. The
GORD and presence of infection. Several reports suggested that most powerful acid inhibitor is IL-1β, with its effect mediated through
H. pylori-positive patients were less likely to have endoscopic and/or the IL-1 receptor on parietal cells.
19,20
TNF-α also has acid inhibitory
histological changes, and, when present, the severity of oesophagitis properties, although weaker than those of IL-1.
21
was lower than in those who were H. pylori-negative.
7
A meta-analysis
of studies addressing H. pylori status in patients with Barrett’s Acid secretion in H. pylori-infected patients depends not only on
metaplasia and oesophageal carcinoma showed that in infected mechanisms leading to hypergastrinaemia, but also on the pattern of
patients the prevalence of neoplasia was lower.
8
Moreover, some gastritis. Antrum-predominant gastritis increases gastric secretion,
investigators suggested that especially Cag A-positive H. pylori strains, while corpus-predominant gastritis is associated with reduced gastric
which are strongly associated with pangastritis, may have a particularly acid secretion and both may return to normal after eradication. It is
protective role against oesophageal neoplasia development.
9-11
worth noting that corpus-predominant gastritis with lower acid output
Unfortunately, these same strains are suspected to promote gastric and secondary hypergastrinaemia, which leads to increased LOS
adenocarcinoma. The evidence presented above has led some authors pressure, is the condition where the GORD symptoms are most
to propose a general ‘protective’ role of H. pylori infection against the unlikely.
16
In contrast, antral-predominant gastritis with increased
development of oesophageal diseases. The underlying mechanisms are gastric acid output may result in duodenal ulcer in patients with
possibly connected to decreased acid secretion, production of competent OGJ and adequate gastric emptying, or in GORD
ammonium and augmentation of the GOJ due to proximal gastritis.
However, some other studies did not find any correlation between
The primary pathway by which H. pylori
H. pylori status and the severity of oesophagitis or histological
parameters in either NERD or RO groups.
12,13
Recent data from a Greek
influences the pathogenesis of gastro-
population show that H. pylori infection is frequent in GORD and that
oesophageal reflux disease is modification
eradication leads to better control of symptoms and improves
oesophagitis.
14
Moreover, there were some reports about marked
of gastric secretion and, consequently,
cardia inflammation associated with H. pylori infection and increasing
oesophageal refluxate content.
severity of oesophagitis positively correlating with the density of the
bacteria in the gastric antrum and infection activity.
15
The mechanisms
that may lead to GORD development in H. pylori-positive patients are: symptoms, even with RO, in patients in whom these mechanisms are
bacterial cytotoxins causing oesophageal epithelium injury; cardiac impaired. Overall, these results indicate differences in pathogenesis
inflammation causing sphincter weakness; increased acid secretion within a group of patients with Helicobacter-induced gastritis.
due to antral gastritis; and delayed gastric emptying.
Helicobacter pylori Infection and
Therefore, the relationship between H. pylori and GORD remains Gastric Neuroendocrine Secretion
controversial and probably relies on multiple mechanisms triggered The inflammatory and immune response induced by H. pylori affects
by the infection. Occurrence and severity of GORD in H. pylori-positive various cell types in gastric mucosa that are important for gastric
patients is the net effect of those mechanisms and depends on host secretion, such as SS, G, chief and parietal cells. As mentioned above,
defence and bacteria-related factors. H. pylori gastritis causes a reduction in mucosal somatostatin levels
EUROPEAN GASTROENTEROLOGY & HEPATOLOGY REVIEW 59
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76