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Ajg 1998292 A
Ajg 1998292 A
Ajg 1998292 A
h
1
(range 00.05
10.9) vs 1.64 mmol H
h
1
(range 0.078.22). The median
observed PAO value in the H. pylori-positive group was
26.75 mmol H
h
1
(range 0.17556.03) vs 26.11 mmol
H
h
1
(range 20.2938.91) in the H. pylori-negative group.
The respective calculated MAO data derived from the fit of
the dose response curve were 24.11 mmol H
h
1
(range
0.2168.26) vs 27.87 mmol H
h
1
(range 22.6141.03).
There was a positive correlation between BAO and MAO
values of both groups (H. pylori-positive, p 0.0088, H.
pylori-negative, p 0.0151). The median value of the
integrated acid response during the pentagastrin dose-re-
sponse curve (acid-AUC) was 146.4 mmol H
/ 5h (range
0.5307.9 in the H. pylori-positive population vs 140.5
mmol H
h
1
(range 0.2168.26) vs 27.87 mmol H
h
1
(range 22.6141.03), but the difference in the degree of variation within each group was significantly different (p 0.0029).
FIG. 4. Gastritis scores and integrated postprandial gastrin release: In each H. pylori-positive or H. pylori-negative subject the individual combined
inflammatory score (A) as well as the total score for H. pylori colonization density (B) is allocated to the integrated postprandial gastrin value. There was
no significant difference between the gastrin data of the two groups (median 87.4 pmol/L 3h [range 9.22539.9] in the H. pylori-positive subjects and 49.8
pmol/L 3h [range 23.2145.2]) in the H. pylori-negative subjects.
AJG August 1998 EFFECTS OF H. PYLORI ON GASTRITIS 1281
infected control subjects (40). The large variation may well
mask a tendency of H. pylori infection to modify basal acid
secretion. It is, however, evident from the result of the
above-quoted study (22) that a large proportion of otherwise
healthy H. pylori-infected subjects and even DU patients do
not have an elevated basal acid secretion and, in our study,
the degree of variation of BAO-data was similarly large
independent on whether or not the subjects were infected by
H. pylori.
Several studies found no change in MAO or PAO data
after H. pylori eradication (19, 22, 32, 39). Some notewor-
thy observations nevertheless suggest that chronic H. pylori
infection may not be fully devoid of an influence on MAO
or PAO. A considerable proportion of H. pylori-infected
patients not suffering from DU disease have been found to
have high acid secretory values that overlap with those of
DU patients (41). Harris et al. (42) demonstrated a consid-
erable fall in pentagastrin-stimulated PAO in DU patients 6
months after H. pylori eradication. Their observation was,
however, based on seven patients only and the reduction
was substantial in only five subjects; but this was in line
with earlier observations of Moss et al. (43), who found a
decrease in MAO values 1 yr after H. pylori eradication. By
contrast, El-Omar et al. (30) recently reported reversal of
total or near total anacidity through H. pylori eradication in
a subgroup of nonulcer patients with corpus predominant
gastritis. The latter finding helps to appreciate better the
observations made by Chandrakumaran et al. (45) that
MAO was lower in both H. pylori-infected DU and non-DU
patients in comparison with the data of respective control
groups. This is in line with earlier observations made con-
cerning male patients by Katelaris et al. (46). These appar-
ently contradictory findings make it likely that H. pylori
infection can lead to either an increase or decrease of MAO
values in subgroups of patients and thus may lead to dis-
cordant results in studies with small patient samples. On the
other hand, the disparate effects that H. pylori eradication
can exert on MAO may compensate each other in studies
with larger samples and thus obscure the inconsistent
changes that chronic H. pylori infection may exert on max-
imum acid secretory capacity of the stomach. Circumstantial
evidence for such a hypothesis is supplied by our observa-
tion that MAO data showed a significantly larger variation
in the H. pylori-infected subjects, whereby more than 50%
of the values of the H. pylori-positive subjects were either
below or above the range of the noninfected subjects. In line
with all other studies our data show, however, unequivo-
cally that many H. pylori-infected subjects have normal
MAO data and that this even relates in our population to the
basal and postprandial gastrin values.
There are at least two possible mechanisms through
which H. pylori infection could increase or decrease maxi-
mum acid output. This is either through a change in the
number of parietal cells or ECL cells or through a modifi-
cation of the function of these highly specialized cells, by H.
pylori toxins or by inflammatory mediators. Even though
there is no unequivocal evidence available that H. pylori
infection can directly enhance the parietal cell or ECL mass,
it is, however, well established that a subset of H. pylori-
infected, usually asymptomatic, patients develop a special
form of chronic multifocal atrophic gastritis (MAG type,
according to the classification of Correa [47]) involving
both the mucosa of the gastric antrum and corpus, leading to
a gradual reduction of epithelial glandular structures, with
permanent loss of the parietal cells, associated with hypo- or
even total achlorhydria (16, 17, 30, 44, 48). The proportion
of such patients appears to be higher in older subjects and
relatively large in the presence of high H. pylori prevalence
(37), and it is less frequently observed in populations with
a lower H. pylori prevalence (14). In our study performed in
a country where H. pylori prevalence is 30% (49), only
one of 14 H. pylori-positive subjects fell into this category
and, in contrast to previous observations (30, 50), the ma-
jority of our nonulcer patients had antral predominant gas-
tritis, the type of gastritis often encountered in DU disease
(40, 41). It is thus more likely that secretory products of H.
pylori (51) or the toxin-induced inflammatory response (52)
did lead to either an enhancement or attenuation in the
maximum acid secretory capacity of the parietal cell in some
of our patients. There is convincing evidence available that
subtotal to total loss of acid secretion can occur after acute
H. pylori infection (5355). Despite persistence of H. pylori
infection and histological gastritis, acute hypochlorhydria
generally resolves spontaneously (16). The mechanisms
through which H. pylori infection modifies the acid output
is not yet fully elucidated, but the rapid partial reversibility
of anacidity observed in patients with advanced gastritis
(30) clearly underlines the existence of the inhibition of the
parietal cell through H. pylori toxins or its inflammatory
mediators, even in patients with long-standing chronic in-
fection.
There is no indication from this and the majority of
previous studies that H. pylori enhances the sensitivity of
the parietal cell to gastrin in non-DU patients (35, 39, 56)
and it is noteworthy that several previous studies using
histamine and pentagastrin could not confirm a difference in
sensitivity to stimulation between DUs and control subjects
(5658). In this context, it is of particular interest that in a
recent study of the McColl group of Glasgow (44), volun-
teers not infected with H. pylori had an equal sensitivity to
gastrin as DU patients, whereas this was 2-fold lower in H.
pylori infected healthy volunteers, thus indicating that the
difference in gastrin sensitivity between DU and non-DU
patients may not be due to an increase in the sensitivity of
ulcer patients but rather to a reduction of this parameter in
H. pylori infected, nonulcer patients. Their technology used
to establish the gastrin sensitivity differed, however, from
that used in this and many previous studies and it was more
sophisticated. They measured plasma gastrin before and
repeatedly during the gastrin infusion in each individual
with an antibody that detects not only endogenous gastrin 17
but also gastrin 34. Plasma gastrin was plotted in each
1282 HURLIMANN et al. AJG Vol. 93, No. 8, 1998
individual against acid output at each measuring point of the
dose-response curve. By contrast the pentagastrin concen-
tration of the infusate was the standard in our study. The
advantage of their method is that it corrects for the overall
increase of basal gastrin in H. pylori-infected subjects. It can
thus not be fully excluded that our technique overestimated
gastrin sensitvity in the H. pylori-infected subjects who in
many previous studies have been shown to have increased
basal gastrin levels (18, 19, 21, 23, 60). Because, in the
present study only few H. pylori-positive individuals had
basal gastrin levels above the range observed in H. pylori-
negative subjects it is unlikely that this difference in meth-
odology fully explains the conflict between the results of the
two studies. It is more likely that differences in the preva-
lence of subforms of gastritis were responsible for the dis-
cordant results, and the Glasgow group has putatively linked
(44) the impairment of gastrin sensitivity in their H. pylori-
positive nonulcer patients to atrophic gastritis within the
gastric corpus, which previously had been observed in non-
ulcer patients (30, 50). The absence of a decreased gastrin
sensitivity in our H. pylori-infected nonulcer patients, who
all except one only had a mild gastric corpus gastritis,
supplies some indirect support for this hypothesis. Simi-
larly, the only mild and insignificant elevation of gastrin as
observed in our H. pylori-infected subjects may also be
related to the low grade of gastric corpus gastritis, because
in nonulcer patients excessive gastrin release is especially
favored by atrophy of the corpus mucosa (8).
Difference in virulence of H. pylori strains has been
considered as a putative explanation as to why only a
minority of DU patients develop peptic ulcers, inasmuch as
it has been shown that patients who develop DU disease are
more likely to be infected with the more aggressive, CagA-
positive strains of H. pylori, which are associated with
enhanced inflammatory responses (61). These strains, how-
ever, have been shown not to disturb gastric function to a
greater degree than do CagA-negative strains (61), but they
are likely to cause greater mucosal damage and hence
weaken the ability of the mucosa to withstand the increased
levels of acid induced by H. pylori infection. In this context
it is noteworthy that the risk for developing gastric cancer is
approximately 4-fold less in DU patients than in the general
population (62), whereas it is considerably higher in patients
with MAG-type gastritis (14, 37).
It is thus more likely that host-related mechanisms, pos-
sibly of genetic origin, are causally related to the fact that
only a small proportion of H. pylori-positive subjects de-
velop significant pathology such as PUD or gastric carci-
noma. Theoretically, the tendency toward a lower or higher
MAO could help to differentiate the two groups early, as
DU disease is expected to occur in subjects with a high
MAO, whereas a low acid output would favor the later
occurrence of a gastric malignancy.
Our data supply some indirect evidence that the notori-
ously large overlap between MAO or PAO data of DU
patients and healthy subjects, which intrigued many ob-
servers before the pathogenic role of H. pylori had been
established (1, 2, 5), may be related, at least in part, to the
fact that many of the healthy subjects were infected by H.
pylori. The significantly greater range of the MAO data
among H. pylori-infected nonulcer patients points toward
the necessity to establish new control data in large groups of
subjects who, in the absence of H. pylori infection, have a
really healthy mucosa both in the gastric antrum and corpus.
It would be of great value to extend such studies to all other
acid secretory parameters and also to review the time-
honored concept of the direct correlation between MAO
data and the parietal cell mass (6).
In conclusion, the results of this study suggest that a large
proportion of H. pylori-infected nonulcer patients have no
abnormality in their gastrin release and in conventional acid
secretory parameters such as BAO, MAO, and sensitivity of
the parietal cell to gastrin, despite various degrees of antral
predominant gastritis. However, maximum acid output of H.
pylori-infected nonulcer subjects showed a considerably
larger variation than in noninfected subjects. Furthermore,
the relatively equal deviation of the data of infected subjects
above and below the range of the healthy control subjects
can be reconciled with previous discordant observations that
H. pylori infection can induce either an increase or a de-
crease of maximum acid secretory capacity of the parietal
cells in subgroups of patients. It appears unlikely that a
difference in the parietal cell mass is the exclusive reason
for the larger variation of MAO data of H. pylori-infected
subjects.
ACKNOWLEDGMENT
We would like to thank Prof. I.N. Marks, Cape Town, and
Prof. K.E.L. McColl for valuable suggestions with the
manuscript.
Reprint requests and correspondence: F. Halter, M.D., F.R.C.P., Edin,
Visiting Professor, Division of Gastroenterology, UCI Medical Center, 101
The City Drive, Bl. Dg 53, Route 81, Orange, CA 92868.
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