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H. pylori in arabs, final not published
1. Helicobacter pylori in Arabs; clinical aspects and related diseases
in comparative study in three Arabian countries.
Shendy Mohammed Shendy*, Naema I. El-Ashry** and Nihal M.El-Assly**
Tropical medicine department* and Clinical Chemistry department, Theodor Bilharz Research
Institute
Abstract:
Helicobacter pylori represents one of the most common infections worldwide. It has been
established as an etiologic factor in the development of peptic ulcer disease and chronic gastritis;
and associated firmly with development of gastric neoplasia, including gastric adenocarcinomas
and gastric mucosa-associated lymphoid tissue lymphomas. Several extradigestive pathologies have
been linked to H. pylori infection including cardiovascular, cutaneous, autoimmune, esophageal
and other diseases such as sideropenic anaemia, growth retardation, and extragastric MALT-lymphoma.
The aim of this work is to evaluate the contribution of H. pylori infection to the
uncommon; digestive and extra-digestive; manifestations of patients in GIT clinics in some Arabian
countries. Patients and methods: a total of 623 H pylori positive patients from three Arabian
countries including 225 Egyptian patients, 188 Kuwait patients and 210 Saudiai patients were
studied and evaluated for all the possible manifestations of this infection. Evaluation was done by
history, medical examination, routine and specific laboratory investigations, endoscopic and
histopathological diagnosis. Follow up after eradication was done to evaluate the response and
improvement of such manifestations. Results: this study included 339 males and 274 females
distributed in the three countries. Recurrent H pylori infection was found in 10.9 % of all patients
and was significantly more common in Saudi patients and associated with significantly higher
incidence of thyroid dysfunction and pancreatitis. Mouth ulcers, vertigo, diabetes, gastric polyps
and low serum iron were significantly more common in Egyptian patients than other population.
Constipation, history of atypical chest pain, pancreatitis, thyroid dysfunction and ALT elevation
were significantly more common in Saudi patients than other populations. Presence of GERD and
migraine were found significantly more common in both Saudi and Kuwaiti than Egyptian patients.
Diabetes mellitus was one of the commonest associated manifestations in this study and was found
in 16.5 % of all patients. Duodenal ulcer was found significantly more common in younger age
group. Autoimmune haemolytic anaemia was found the only disease associated with significantly
higher Cag A positivity. Constipation was also common in this population (11.9 % of all patients)
and was directly correlated with the presence and severity of gastritis. Pancreatitis was directly
correlated with history of past infection, gastric ulcer, GIT malignancy, gastric outlet obstruction,
arthritis and skin rash. Low serum iron and hemoglobin were more significant in patients with
peptic ulcer disease and GIT malignancy. After eradication of infection, marked improvement
during follow up was noticed in patients with skin rash (28/37), mouth ulcer (37/59), and
constipation (51/73) while mild to moderate improvement was noticed in those with migraine
(11/260 and vertigo (19/49). Also, highly significant increase in serum iron and hemoglobin levels (P
< 0.001) was found in all patients after eradication of infection when analyzed altogether and as
separate groups without iron supplementation. The most sensitive and specific diagnostic tests for
H pylori in this cohort was the microscopic examination, followed by rapid urease test; both depend
on gastric biopsies. Conclusion: It is concluded from this study that H pylori infection is present in
most Arabian countries nearly with similar, but of somewhat variable extent, manifestations wither
digestive or extradigestive. The associated extradigestive manifestations described cannot be
attributed to H pylori in all cases, but it is recommended to screen for this infection and eradicate it
particularly if there are additional upper GIT complaints. The presence of GERD should not affect
the decision of treatment of this infection. Finally, diagnosis and treatment of H pylori might be
considered in the workup in the management of diseases with autoimmune pathogenesis such as
ITP, autoimmune haemolytic anaemia, skin diseases, thyroid dysfunction, diabetes mellitus, and
others.
2. Introduction:
Helicobacter pylori represents one of the most common infections worldwide. Infection with
this microaerobic, gram-negative bacterium has been established as an etiologic factor in the
development of peptic ulcer disease and chronic gastritis. In addition, H pylori infection has been
associated firmly with the development of gastric neoplasia, including gastric adenocarcinomas
and gastric mucosa-associated lymphoid tissue lymphomas ( Dunn et al., 1997; Eslick et al. 1999;
Weir et al., 1999 and James, 2003).
Chronic gastritis due to H pylori infection may be separated into distinct, clinically relevant
phenotypes (Rubin 1997 and Faller and Kirchner 2001). Nonatrophic pangastritis occurs in the
majority of H pylori-infected individuals with no predisposition to peptic ulcer disease or gastric
atrophy. Prominent mucosal inflammation in chronic active gastritis often is evident in the antrum
(antral-predominant gastritis), predisposing to hyperacidity and duodenal ulcer disease. In contrast,
multifocal atrophic pangastritis and atrophic corpus-predominant gastritis result from long-standing
infection and are characterized by glandular atrophy, intestinal metaplasia, and sparse
inflammatory cells. Both forms of atrophic gastritis and the presence of intestinal metaplasia are
associated with an increased risk of gastric adenocarcinoma (Uemura et al. 2001). In addition,
lymphocytic and granulomatous gastritis have been linked with H pylori infection. Although
isolated cases of idiopathic granulomatous gastritis have been demonstrated in association with H
pylori infection, it is unclear whether H pylori has an important role in the development of gastric
granuloma (Shapiro et al., 1996).
Studies in developed countries showed that the overall prevalence of H pylori infection ranges
from 25% to 30% (Dunn et al., 1997) and the seroprevalence increases with age, ranging from 5%
to 27% in early childhood to levels exceeding 50% in adults older than 50 years. with an
acquisition rate in adults of 3% to 4% per decade (Cullen et al., 1993, Kosunen et al., 1997 and
Sipponen et al., 1996).
More than 90% of duodenal ulcers are associated with H pylori, which is present in highest
concentrations in the gastric antrum. A proximal-distal gradient of increasing organism densities
exists along the corpus and antrum in duodenal ulcer disease and extends toward the transitional
zone and gastroduodenal junction. Consequently, virtually all patients with duodenal ulcer disease
have chronic, active, antral-predominant gastritis. With respect to duodenal ulcer disease,
endoscopic visualization of the ulcer may be sufficient for diagnosis (Greenberg et al., 1996).
Diagnostic confirmation of the presence of H pylori necessitates biopsy sampling of the gastric
corpus and antrum. In contrast, the diagnostic evaluation of gastric ulcers requires biopsy
specimens of the ulcer base and areas adjacent to gross ulceration to assess the histological features
for the presence of atrophic or neoplastic changes. Adjacent mucosa is evaluated directly for the
presence of concomitant atrophy, dysplasia, intestinal metaplasia, or gastric adenocarcinoma
(Kuipers, 1997).
Several extradigestive pathologies have been linked to H. pylori infection including
cardiovascular, cutaneous, autoimmune, esophageal and other diseases such as sideropenic
anaemia, growth retardation, and extragastric MALT-lymphoma. The potential role of H. pylori
infection in the pathogenesis of these extradigestive disorders has been based on facts that 1) local
gastric inflammation may exert systemic effects, 2) chronic infection of gastric mucosa induces
immune responses that are able to cause the lesions remote to primary site of infection and 3) H.
pylori eradication improves the extradigestive disorders (Konturek et al., 1999).
3. The main aim of this work is to evaluate the contribution of H. pylori infection to the
uncommon; digestive and extra-digestive; manifestations of patients in GIT clinics in some
Arabian countries. The secondary aim is to give a good clinical expectation to such manifestations
and if it is essential to eradicate this infection or not.
Materials and methods:
Patients from three countries were subjected to evaluation in this study. These countries
included Egypt (patients attending some centers in Cairo; 225 patients), Kuwait (patients attending
gastrointestinal tract clinic in El-Moasah hospital, Salemia, Kuwait; 188 patients) and Saudia
Arabia (Elite medical center, El-Olia, Riyadh; 210). Patients presented with symptoms that may be
attributed to H pylori infection such as dyspepsia, upper abdominal pain, heartburn, flatulence and
distension or colonic disturbance. Some also complained of manifestations not directly related to
upper GIT but were niether explained by other causes nor of typical nature of their origin such as
biliary symptoms, chronic upper respiratory symptoms, bad odour of the mouth ,anorexia &
general fatigue ,dyspeptic ulcers, persistant unexplained elevation of liver enzymes, constipation,
migraine & cluster headache, vertigo, arthralgia, angina, arrhythmia, arthralgia, backache &
urticaria. Patients with any systemic or another obvious cause for their symptoms were excluded.
The following was done for all patients:
1- History and thorough clinical examination
2- CBC, Serum iron, stool and urine analysis
3- C-Reactive Protein, ESR, and serum amylase and lipase in cases suspected of pancreatitis.
4- Liver f. tests, kidney f. tests, fasting blood sugar, and serum lipid profile
5- Abdominal ultrasound, ECG, chest X-ray
6- Hepatitis markers: HCV-Ab, HbsAg, HbcAb, CMV and EBV Abs.
7- Urea-breath test, H. pylori IgG and Cag-A Ab by ELISA
8- Endoscopy when indicated and approved, with gastric biopsies of any lesion found and rapid
urease test (clo test) for all patients.
Inclusion criteria:
1. Patients aging from 8 to 60 years attending GIT clinics in these centers suffering from
digestive or systemic manifestations that may be related to H. pylori infection but not explained by
other diseases.
2. H pylori positivity by at least two tests specific for H pylori.
3. No evidences of hepatic (particularly viral), cardiac, pulmonary, renal, endocrinal (not
including Diabetes), hematological, neurological rheumatologic or biochemical abnormalities.
4. No history of medications with similar side effects.
5. No history of treatment of H pylori or similar drugs in the 6 months before enrollment.
6. Written informed consent for the plan of the research
Treatment with standard therapy was given to all patients. Retreatment of relapsing cases after
at least one month was established using different regimens of quadruple therapy. Follow up of
patients for a period of 3 months up to one year was conducted with repetition of breath test and
serology for H pylori at end of follow up period.
Results:
4. This study included 225 patients from Egypt, 188 patients from Kuwait and 200 patients from
Saudia Arabia. The sex distribution and age of three categories are comparable as shown in table 1
and 2.
Table 1: Number and sex distribution among studied patients.
Egyptian Ptients
sex
Kuwaiti patients
sex
Saudi patients
sex
129 57.3% 103 54.8% 107 53.5%
96 42.7% 85 45.2% 93 46.5%
225 100.0% 188 100.0% 200 100.0%
males
females
Total
Count %
Count %
Count %
group
Table 2: Age distribution among studied patients.
225 31.91 12.122
188 33.43 12.939
200 33.55 11.908
age
age
age
group
Egyptian Ptients
Kuwaiti patients
Saudi patients
N Mean Std. Deviation
No significant differences in age or sex distribution between patients from the three nations as
regards H pylori infection. No correlation between age and all manifestations or diagnostic tests of
H pylori except for duodenal ulcers (indirect correlation; i.e. more in younger age patients) and
constipation (direct correlation; more in older age patients).
Tables 3 and 4: History of previous infection in all patients.
absent
present
211 93.8% 14 6.2%
170 90.4% 18 9.6%
165 82.5% 35 17.5%
group
Egyptian Ptients
Kuwaiti patients
Saudi patients
Count %
Count %
history of previous
infection
546 89.1%
67 10.9%
613 100.0%
absent
present
Total
Count %
History of past H pylori infection was found in 10.9 % of all patients and was significantly
more common in Saudi than Egyptian (P= 0.001) and Kuwaiti patients (P = 0.023).
Nearly all of these H. pylori positive patients complained of upper GIT symptoms including
upper central abdominal pain, discomfort, dyspepsia, flatulence, heartburn, or colonic symptoms.
These symptoms were very common in these patients and improved to a variable extent after
eradication of Infection.
Table 5: some clinical manifestations in all patients studied
5. Skin rash
Mouth Ulcer
Constipation
pancreatitis
576 94.0% 554 90.4% 540 88.1% 590 96.2%
37 6.0% 59 9.6% 73 11.9% 23 3.8%
613 100.0% 613 100.0% 613 100.0% 613 100.0%
absent
present
Total
Count %
Count %
Count %
Count %
Table 6: some clinical manifestations in different groups studied.
210 198 211 217
93.3% 88.0% 93.8% 96.4%
15 27 14 8
6.7% 12.0% 6.2% 3.6%
177 182 170 188
94.1% 96.8% 90.4% 100.0%
11 6 18
5.9% 3.2% 9.6%
189 174 159 185
94.5% 87.0% 79.5% 92.5%
11 26 41 15
5.5% 13.0% 20.5% 7.5%
Count
%
absent
Count
%
present
Count
%
absent
Count
%
present
Count
%
absent
Count
%
present
group
Egyptian Ptients
Kuwaiti patients
Saudi patients
Skin rash Mouth Ulcer Constipation pancreatitis
History or presence of skin rash was found in 18.1 % (37 patients) of all patients, mostly of
urticaria- like nature (28 patients) and rosacea (9 patients). These patients were referred to
Dermatologist to complete their management. Diagnosis of pancreatitis, by history, clinical data
and pancreatic enzymes, was found significantly more common in Saudi than Egyptian (P = 0.009)
and Kuwaiti patients (P = 0.001). Constipation was significantly more common in Saudi than
Egyptian and Kuwaiti patients (P = 0.001) and (P = 0.003) respectively. Mouth ulcers were
significantly more common in Egyptian and Saudi patients than in Kuwaiti patients (P = 0.001).
No statistically significant differences between patient’s categories in other parameters. Except for
autoimmune hemolytic anemia (P = 0.02), no correlation was detected between all these
manifestations and Cag positivity (P > 0.05). There was correlation between presence of
constipation and presence of GIT malignancy and presence and severity of gross and microscopic
gastritis. During follow up after eradication therapy, skin rashes, mouth ulcers and constipation
were markedly improved in 28/37; 37/59 and 51/73 respectively.
Table 7: some autoimmune manifestations in all patients studied.
512 589 605 605 605
83.5% 96.1% 98.7% 98.7% 98.7%
101 24 8 8 8
16.5% 3.9% 1.3% 1.3% 1.3%
613 613 613 613 613
100.0% 100.0% 100.0% 100.0% 100.0%
Count
%
absent
Count
%
present
Count
%
Total
DM Arthritis AI anemia ITP
Sjogren's
Syndrome
Table 8: some autoimmune manifestations in the different groups.
6. 198 216 221 223 222
88.0% 96.0% 98.2% 99.1% 98.7%
27 9 4 2 3
12.0% 4.0% 1.8% .9% 1.3%
160 183 187 185 187
85.1% 97.3% 99.5% 98.4% 99.5%
28 5 1 3 1
14.9% 2.7% .5% 1.6% .5%
154 190 197 197 196
77.0% 95.0% 98.5% 98.5% 98.0%
46 10 3 3 4
23.0% 5.0% 1.5% 1.5% 2.0%
Count
%
absent
Count
%
present
Count
%
absent
Count
%
present
Count
%
absent
Count
%
present
group
Egyptian Ptients
Kuwaiti patients
Saudi patients
DM Arthritis AI anemia ITP
Sjogren's
Syndrome
Table 9: Thyroid dysfunction in all patients.
absent
Count %
hyperthyroidism
Count %
hypothyroidism
Count %
Total
Count %
567 92.5% 23 Thyroid dis 3.8% 23 3.8% 613 100.0%
Table 10: Thyroid dysfunction in different groups.
absent
hyperthyroidism
hypothyroidism
213 94.7% 7 3.1% 5 2.2%
176 93.6% 7 3.7% 5 2.7%
178 89.0% 9 4.5% 13 6.5%
Thyroid dis
Thyroid dis
Thyroid dis
group
Egyptian Ptients
Kuwaiti patients
Saudi patients
Count %
Count %
Count %
Diabetes was the most commonly associated disease detected in these patients. It was found in
16.5% in all patients with the highest association found in Saudi patients. It was found that
diabetes mellitus was significantly more common in Saudi patients than Egyptians (P = 0.003) and
Kuwaitis (P = 0.04) and thyroid diseases were also significantly more common in Saudi patients
than Egyptians (P = 0.02) and more than Kuwaitis but didn’t reach statistical significance (P =
0.07). No statistically significant differences between patient’s categories in other parameters.
Thyroid dysfunction and pancreatitis were found more significant in patients with recurrent H
pylori infection (P = 0.04) and (P = 0.002) respectively. Presence of DM correlated directly and
significantly with the presence of mouth ulcers (P = 0.002) and atypical chest pain (P = 0.001).
Presence of arthritis correlated directly and significantly with the presence of pancreatitis (P =
0.001) and AI hemolytic anemia (P = 0.002). The course of these manifestations is fluctuant and
prolonged; and long follow up was not applicable.
Table 11: some other clinical manifestations in all patients studied.
579 584 577 564 547
94.5% 95.3% 94.1% 92.0% 89.2%
34 29 36 49 66
5.5% 4.7% 5.9% 8.0% 10.8%
613 613 613 613 613
100.0% 100.0% 100.0% 100.0% 100.0%
Count
%
absent
Count
%
present
Count
%
Total
Atypical
chest pain Arrhythmia Migraine Vertigo Headache
Table 12: some other clinical manifestations in different groups studied.
7. 219 217 221 204 197
97.3% 96.4% 98.2% 90.7% 87.6%
6 8 4 21 28
2.7% 3.6% 1.8% 9.3% 12.4%
180 182 173 180 171
95.7% 96.8% 92.0% 95.7% 91.0%
8 6 15 8 17
4.3% 3.2% 8.0% 4.3% 9.0%
180 185 183 180 179
90.0% 92.5% 91.5% 90.0% 89.5%
20 15 17 20 21
10.0% 7.5% 8.5% 10.0% 10.5%
Count
%
absent
Count
%
present
Count
%
absent
Count
%
present
Count
%
absent
Count
%
present
group
Egyptian Ptients
Kuwaiti patients
Saudi patients
Atypical
chest pain Arrhythmia Migraine Vertigo Headache
It was found that history of atypical, non-cardiac chest pain was significantly more common in
Saudi patients than Egyptian (P = 0.003) and Kuwaiti (P = 0.001) patients. The prevalence of such
symptom is low in patients studied (5.5% of all patients).History of migraine was found
significantly more common in Kuwaiti and Saudi patients than Egyptian patients (P = 0.003) and
(P = 0.001) respectively. History of vertigo was significantly more common in Egyptian and Saudi
patients than Kuwaiti patients (P = 0.04) and (P = 0.03) respectively. No statistically significant
differences between patient’s categories in other parameters. After eradication, migraine and
vertigo showed marked improvement in 11/26 and 19/49 respectively.
Two cases in Saudi patients had moderate form of ulcerative colitis in association with severe
gastritis due to H pylori. Eradication and specific treatment of UC resulted in complete cure of
patients and withdrawal of treatment in few weeks (average 9.4 weeks).
Table 13: Gastroduodenal manifestations and complications in all patients.
569 557 554 600 605
92.8% 90.9% 90.4% 97.9% 98.7%
44 56 59 13 8
7.2% 9.1% 9.6% 2.1% 1.3%
613 613 613 613 613
100.0% 100.0% 100.0% 100.0% 100.0%
Count
%
Absent
Count
%
Present
Count
%
Total
Gastric ulcer
Duodenal
ulcer
Gastric
Polyps
Bleeding
from ulcers
Gastric outlet
obstruction
Table 14: Gastroduodenal manifestations and complications in different groups.
Gastric ulcer
Duodenal ulcer
Gastric Polyps
Bleeding from ulcers
Gastric outlet
obstruction
204 90.7% 202 89.8% 190 84.4% 218 96.9% 222 98.7%
21 9.3% 23 10.2% 35 15.6% 7 3.1% 3 1.3%
172 91.5% 172 91.5% 180 95.7% 185 98.4% 186 98.9%
16 8.5% 16 8.5% 8 4.3% 3 1.6% 2 1.1%
193 96.5% 183 91.5% 184 92.0% 197 98.5% 197 98.5%
7 3.5% 17 8.5% 16 8.0% 3 1.5% 3 1.5%
Absent
Present
Absent
Present
Absent
Present
group
Egyptian Ptients
Kuwaiti patients
Saudi patients
Count %
Count %
Count %
Count %
Count %
The prevalence of peptic ulcer disease among the three nations was not statistically significant.
Gastric ulcer was detected in 7.2 % and duodenal ulcer in 9.1 of all patients (both in 16.3%).
Gastric polyps are found statistically more significant in Egyptian patients than Kuwaiti and Saudi
8. patients (P = 0.017) and more in Saudi than Kuwait patients but not statistically significant (P =
0.127). There is direct correlation between presence of pancreatitis and all of gastric outlet
obstruction, gastric ulcer, gastrointestinal malignancy, history of recurrent H pylori infection,
arthritis and skin rash.
Table 15: presence and severity of Gastro-oesophageal reflux in all patients.
376 73 65 38 21 36 4
61.3% 11.9% 10.6% 6.2% 3.4% 5.9% .7%
Count
%
GERD,
grade
Absent Grade 1 Grade 2 Grade 3 Grade 4
Any grade
with Barrett'
esophagus Stricture
Table 18: presence and severity of Gastro-oesophageal reflux in different patients.
Absent
Grade 1
Grade 2
Grade 3
Grade 4
Any grade with Barrett'
esophagus
Stricture
158 70.2% 30 13.3% 18 8.0% 4 1.8% 3 1.3% 10 4.4% 2 .9%
112 59.6% 18 9.6% 30 16.0% 14 7.4% 3 1.6% 10 5.3% 1 .5%
106 53.0% 25 12.5% 17 8.5% 20 10.0% 15 7.5% 16 8.0% 1 .5%
GERD, grade
GERD, grade
GERD, grade
group
Egyptian Ptients
Patients from Kuwait
Saudi patients
Count %
Count %
Count %
Count %
Count %
Count %
Count %
The presence and severity of GERD are more significant in Saudi and Kuwaiti than Egyptian
patients and in Saudi than Kuwaiti patients. The overall prevalence of GERD of all grades in such
population is 38.83% (233 patients). Most of cases (183) showed no changes in their symptoms
after treatment of H pylori. Few cases (23 patients) showed worsening and few cases showed little
improvement after eradication (27 patients).
Table 19: Gastritis in all patients as diagnosed endoscopically.
177 274 162
28.9% 44.7% 26.4%
Count
%
Macroscopic
gastritis
None Antral diffuse
Table 20: Gastritis in different groups as diagnosed endoscopically.
59 107 59
26.2% 47.6% 26.2%
58 81 49
30.9% 43.1% 26.1%
60 86 54
30.0% 43.0% 27.0%
Count
%
Macroscopic
gastritis
Egyptian
Ptients
Count
%
Macroscopic
gastritis
Patients from
Kuwait
Count
%
Macroscopic
gastritis
Saudi patients
group
None Antral diffuse
Table 21: Gastritis in all patients as diagnosed by histopathology of antral biopsies.
54 159 213 125 62
8.8% 25.9% 34.7% 20.4% 10.1%
Count
%
Microscopic
gastritis
Absent Mild Moderate Severe
With atrophy,
intestinal
metaplasia+/-
dysplasia
Table 22: Gastritis in different groups as diagnosed by histopathology of antral biopsies.
9. 16 55 85 46 23
7.1% 24.4% 37.8% 20.4% 10.2%
11 57 66 36 18
5.9% 30.3% 35.1% 19.1% 9.6%
27 47 62 43 21
13.5% 23.5% 31.0% 21.5% 10.5%
Count
%
Microscopic
gastritis
Egyptian
Ptients
Count
%
Microscopic
gastritis
Patients from
Kuwait
Count
%
Microscopic
gastritis
Saudi patients
group
Absent Mild Moderate Severe
With atrophy,
intestinal
metaplasia+/-
dysplasia
The presence and grades of severity of gastritis whether gross as seen during endoscopy or
microscopic as examined by gastric biopsies, showed no significant differences between all
patients studied.
Table 23: Presence and types of cholecystitis in different patients.
202 9 14
174 7 7
182 14 4
Cholecystitis Count
Cholecystitis Count
Cholecystitis Count
group
Egyptian Ptients
Patients from Kuwait
Saudi patients
Absent Calcular Non-Calcular
No significant differences in the presence of cholecystitis (as diagnosed clinically and by
ultrasound) whether calcular or non-calcular, between patient’s categories. Calcular cholecystitis
in these patients was present in 4.9% in all patients.
Table 24: Types of malignancies detected in patients of different groups.
Absent
Esophageal
Gastric
duodenal
Lymphoma
213 94.7% 5 2.2% 3 1.3% 1 .4% 3 1.3%
180 95.7% 1 .5% 2 1.1% 2 1.1% 3 1.6%
192 96.0% 2 1.0% 3 1.5% 1 .5% 2 1.0%
Egyptian Ptients
Kuwaiti patients
Saudi patients
group
Count %
Count %
Count %
Count %
Count %
Malignancies diagnosed in these patients included 7 oesophageal, 8 gastric adenocarcinoma, 8
gastric lymphoma, and 4 duodenal adenocarcinoma. All were advanced and managed in the usual
way of such tumors.
Table 25: Results of different tests used to diagnose H pylori in all patients.
Anti-H Pylori Ab
Breath test
Rapid Urease T.
H pylori by
Microscopic E.
191 84.9% 183 81.3% 213 94.7% 218
34 15.1% 42 18.7% 12 5.3% 7
156 83.0% 144 76.6% 178 94.7% 182
32 17.0% 44 23.4% 10 5.3% 6
161 80.5% 151 75.5% 184 92.0% 188
39 19.5% 49 24.5% 16 8.0% 12
positive
negative
positive
negative
positive
negative
group
Egyptian Ptients
Patients from Kuwait
Saudi patients
Count %
Count %
Count %
Count
No differences between patient’s categories in the positivity of different diagnostic tests used
to diagnose H pylori infection. The most sensitive test for diagnosis in all patients and different
10. patient’s categories is the microscopic examination of gastric biopsies which is statistically more
positive than all other tests. It is significantly more positive than serology and breath tests but not
rapid urease test when comparison is done according patient’s categories. Rapid urease test on
gastric biopsies is found more significantly positive than breath test and serology in all patients and
different categories. Antibody positivity is more significant than breath test only if compared
between all patients. Breath test showed significant direct correlation with all other tests and Cag
positivity. Also, rapid urease test, breath test and microscopic detection of the bacteria correlated
directly with each others but not with antibody positivity.
Table 26: Cag A positivity in all groups
Cag positivity * group Crosstabulation
57 22 29 108
25.3% 11.7% 14.5% 17.6%
168 166 171 505
74.7% 88.3% 85.5% 82.4%
225 188 200 613
100.0% 100.0% 100.0% 100.0%
Count
% within group
Count
% within group
Count
% within group
ngative
positive
Cag positivity
Total
Egyptian
Ptients
Patients
from Kuwait
Saudi
patients
group
Total
Cag positivity was significantly higher in Saudi and Kuwaiti patients than Egyptian patients (P
= 0.001) and (P = 0.005). Cag positivity showed significant correlation with breath test positivity
and presence of autoimmune hemolytic anemia but no correlation with all other tests or
manifestation of H pylori infection.
Table 21: Serum iron (μg /dl); in total patients; (Normal value: 37-170 in females, 49-181 in
males) before and after eradication of H pylori.
S. iron before eradication
S. iron after Eradication
401 65.4% 559 91.3%
212 34.6% 53 8.7%
Above 50
Below 50
Count %
Count %
Table 22: Serum iron (μg /dl); in all groups (Normal value: 37-170 in females, 49-181 in males).
Egyptian Ptients
S iron
Patients from Kuwait
S iron
Saudi patients
S iron
161 71.6% 113 60.1% 127 63.5%
64 28.4% 75 39.9% 73 36.5%
Above 50
Below 50
Count %
Count %
Count %
group
Table 23: Blood Hb (g /dl) before and after treatment; in all patients.
11. Hb level before
eradication
Hb level after
eradication
398 64.9% 531 86.6%
215 35.1% 82 13.4%
Above 10 gm
Below 10 gm
Count %
Count %
Table 23: Blood Hb (g /dl) before and after treatment; in all groups.
Egyptian Ptients
Patients from Kuwait
Saudi patients
142 192 125 164 131 175
63.1% 85.3% 66.5% 87.2% 65.5% 87.5%
83 33 63 24 69 25
36.9% 14.7% 33.5% 12.8% 34.5% 12.5%
Count
%
Above 10
gm
Count
%
Below 10
gm
Hb level
before
eradication
Hb level after
eradication
Hb level
before
eradication
Hb level after
eradication
Hb level
before
eradication
Hb level after
eradication
group
No significant differences between different patient’s categories in serum iron or hemoglobin
levels except for significantly less serum iron in Egyptian patients than patients from Kuwait
(P=0.014). Low serum iron showed significant correlation with hemoglobin low level. Serum iron
and hemoglobin levels were significantly lower in females than males. Serum iron level was
significantly lower in patients with peptic ulcers (P = 0.014) and GIT malignancy (P = 0.011).
Hemoglobin level was significantly lower in patients with thyroid disease (P = 0.04). Statistically,
highly significant increase in serum iron and hemoglobin levels (P < 0.001) was found in all
patients after eradication of infection when analyzed altogether and as separate groups without iron
supplementation.
Table 24: Serum ALT (μg /dl); before and after treatment; in all patients.
ALT before eradication
ALT after eradication
437 71.3% 494 81.0%
98 16.0% 85 13.9%
78 12.7% 31 5.1%
normal
Less than 2
folds increase
More than 2
folds increase
Count %
Count %
Table 25: Serum ALT (μg /dl); before and after treatment; in all groups.
12. Egyptian Ptients
Patients from Kuwait
Saudi patients
176 188 128 155 133 151
78.2% 84.7% 68.1% 82.4% 66.5% 75.5%
35 24 39 24 24 37
15.6% 10.8% 20.7% 12.8% 12.0% 18.5%
14 10 21 9 43 12
6.2% 4.5% 11.2% 4.8% 21.5% 6.0%
Count
%
normal
Count
%
Less than 2 folds
increase
Count
%
More than 2 folds
increase
ALT before
eradication
ALT after
eradication
ALT before
eradication
ALT after
eradication
ALT before
eradication
ALT after
eradication
group
ALT was found elevated in 28.7 % with more affection in Saudi, then Kuwaiti than Egyptian
patients but not statistically significant. Follow up of this parameter was not done. Statistically,
highly significant decrease in ALT level (P < 0.001) was found in all patients after eradication of
infection when analyzed altogether and as separate groups
Discussion
The prevalence of H pylori infection varies widely by geographic area, age, race, and
ethnicity. Rates appear to be higher in developing than in developed countries, with most of the
infections occurring during childhood, and they seem to be decreasing with improvements in
hygiene practices. Infection probably occurs via feco-oral route which is a common way in areas
with low socioeconomic standard. However, this infection remains common also in well
civilized areas and developed countries. Adequate nutritional status, especially frequent
consumption of fruits and vegetables and of vitamin C, appears to protect against infection with
H pylori. In contrast, food prepared under less than ideal conditions or exposed to contaminated
water or soil may increase the risk. Overall, inadequate sanitation practices, low social class, and
crowded or high-density living conditions seem to be related to a higher prevalence of H pylori
infection (Brown, 2000). It can cause a wide spectrum of manifestations including those related
to local infection in the upper gastrointestinal tract and those related to the presence of chronic
infection in the body with systemic manifestations.
In the patients of this study, the mean age seemed to be low with the mean age around 33 years
(32.91). It probably depends on the rate of exposure to infection in the active age group. It can be
due to coincidence of H. pylori epidemic with this age, while older age has escaped such
exposure in the community.
The sex distribution is somewhat towards the male side probably due to more exposure
through taking meals outside in the work. However, the difference is not significant and females
are equally susceptible and seem to be more manifest. In this study, sex was only related to low
serum iron and low hemoglobin level which were more in females. This finding is probably
related to iron loss in menstrual blood in addition to iron malabsorption and iron loss due to
gastric pathology. Low serum iron was detected in 34.6% of all patients with no differences
between the three groups. In previous studies, it was found that H pylori infection can contribute
to iron deficiency anaemia, and that infection should be suspected when the iron deficiency
anaemia is refractory to iron administration. It was also proposed that treatment for iron
deficiency anaemia coexistent with H pylori infection should include H pylori eradication
(Sanstead et al., 1971; Chwang et al., 1988; Hallberg et al., 1993 and Yon Ho Choe 2000). In one
of these studies, eradication of H pylori was followed by significant increase in serum iron;
ferritin and hemoglobin levels in all patients (Choe et al., 2001). Thus, this study supports such
13. findings of association of iron deficiency anemia and H pylori infection that necessitates
eradication to correct these abnormalities. Peptic ulcers and GIT malignancy cause more
decrease in serum iron level. Also and as expected, it was found that hemoglobin level was
significantly lower in patients with thyroid disease. In another study, it was found that
hemoglobin and MCV values rose significantly compared with baseline values after H. pylori
eradication without iron supplementation in children with iron deficiency anaemia (IDA).
Ferritin values increased significantly after H. pylori eradication in children with iron deficiency
(ID). It was concluded that complete recovery of ID and IDA can be achieved with H. pylori
eradication without iron supplementation in children with H. pylori infection (Kurekci et al.,
2005). Therefore, iron status should be evaluated in such patients and corrected in addition to H
pylori eradication.
History of past H pylori infection was found in 10.9 % of all patients. Recurrent infection is
significantly more seen in Saudia Arabia than the other two countries. This can be due to more
exposure, higher prevalence of infection in the community, more eating outside door, drug
resistance due to frequent use of effective antibiotics for other infections or incomplete
treatment. Thyroid dysfunction and pancreatitis were significantly more common with history of
previous infection. This may be due to immune pressure exerted by repeated or prolonged
infection or prolonged exposure of pancreas to the bacteria or its toxins or inflammatory
mediators if there is role for such exposure. Similar association was found between arthritis,
autoimmune hemolytic anemia and pancreatitis, and between diabetes mellitus and mouth ulcers.
The percentage of peptic ulcer was as expected without differences in all patients. It was
diagnosed in 7.2% in stomach and in 9.1% in duodenum and gastric polyp was found in 9.6 %.
Bleeding occurred in 2.1% of cases; 8 fro duodenal ulcers and 5 from gastric ulcers. Studies
demonstrated that H. pylori infection was found in more than 90% of patients with duodenal
ulcers, and some 70% of patients with gastric ulcers (Marshal et al., 1985 and Gaham et al.,
1988). The declining incidence and prevalence of peptic ulcer in developed countries has
paralleled the falling prevalence of H. pylori infection, especially in populations with high
infection rates. Only H. pylori eradication is an effective treatment for both duodenal and gastric
ulcers (Xia et al., 2001 and Perez-Aisa et al., 2005).
In this survey, it was found that atypical, non-cardiac chest pain was significantly more
common in Saudi patients than Egyptian and Kuwaiti patients. The prevalence of such symptom
is low in all patients (5.5% of all patients) despite the higher prevalence of GERD in such
population (38.83%). Migraine was found significantly more common in Kuwaiti and Saudi
patients than Egyptian patients. Vertigo was significantly more common in Egyptian and Saudi
patients than Kuwaiti patients. However, the prevalence of such symptoms was low in all
patients studied. Also, there are no convincing evidences that these symptoms are strongly
related to H pylori infection apart from improvement of such symptoms after treatment. Ischemic
chest pain was not investigated in these patients. However, there were many studies and reports
about the relation of H pylori infection and atherosclerosis which is the main cause of coronary
heart disease. Emerging evidence seems to give a potential role for H. pylori in ischemic heart
disease via a cross mimicry between antibodies against heat shock protein 65 which are produced
in the consequence of infection, but which are also expressed in atherosclerotic lesions
(Gasbarrini and Franceschi, 1999). In General, it has been hypothesized that H pylori infection-associated
chronic inflammation leads to elevated plasma levels of fibrinogen, C-reactive
protein, and leukocytes -- all known risk factors for CHD. Other hypotheses include a gastritis
that causes vitamin B deficiency, leading to hyperhomocysteinemia or a stimulated leukocyte
procoagulant activity. None of the four prospective studies examining the relationship between
14. H pylori seropositivity and CHD prevalence has been statistically significant (Folsom, 1998). In
one epidemiological study, it was found that in diabetic men but not in all men, seropositivity
was significantly associated with CHD prevalence but no consistent associations of H pylori
infection with diabetes prevalence or variables of the insulin resistance syndrome were found in
American men aged 40-74 years (Gillum, 2004). The most recent study concluded that: 1) There
is a significant link between CAD and infection with H. pylori, especially expressing CagA
proteins; 2) Patients infected with CagA-positive H. pylori show significantly greater coronary
artery lumen loss and arterial re-stenosis after PTCA with stent implantation; 3) H. pylori
eradication significantly attenuates the reduction in coronary artery lumen in CAD patients after
PTCA possibly due to the elimination of chronic inflammation and the decline in
proinflammatory cytokine release and 4) The identification of DNA in atherosclerotic plaques of
patients with severe CAD supports the hypothesis that infection with H. pylori (especially CagA
positive) may influence the development of atherosclerosis (Kowalski M, 2005). If this study is
supported with more controlled double blind studies; it may revolutionize the prevention and
management of coronary artery disease in such patients particularly of young age.
It was found that constipation correlated directly with the presence and severity of gastritis as
detected by endoscopic examination and gastric biopsies and most of patients improved to a
considerable extent after eradication treatment. The two cases in Saudi patients who had
ulcerative colitis and showed complete cure in few weeks after treatment specific for this disease
in addition to eradication therapy could add this gastrointestinal disease as another probable
association. In another study, H pylori DNA was detected in biopsies of six patients from total of
60 with ulcerative colitis while no one tested positive in 29 controls (Streutker et al., 2004).
Further studies, enrolling a higher number of patients, are needed in order to confirm these
results, to characterize the Helicobacter sp. detected and to assess their role in IBD pathogenesis.
Skin rash of different forms, mostly urticaria and rosacea, were detected in 6% of all patients
with no statistically significant differences between patients studied. Evidence for a potential link
of H. pylori infection exists for chronic urticaria although the data are still conflicting. Thus, the
search for H. pylori should be included in the diagnostic management of chronic urticaria (Wedi
and Kapp, 1999). The bacterium has been implicated also other skin diseases such as rosacea, but
a causal role for the bacterium is missing (Valsecchi et al., 1998; Wustlich et al., 1999; Pakodi et
al., 2000 and Greaves 2000). Only single of few cases have been reported so far for other skin
diseases such as hereditary or acquired angioedema due to C1-esterase inhibitor deficiency,
systemic sclerosis, Schonlein-Henoch purpura, Sjogren's syndrome, Behcet’s disease, sweet's
syndrome, and atopic dermatitis. Caution must be taken not to accuse H. pylori as the infectious
agent responsible for every disease, particularly since H. pylori infection is very common.
Although from an epidemiological and morphological view the skin diseases to which H. pylori
has been linked seem to be completely different. It is striking that in most of them an
autoimmune pathogenesis is suspected or considerable vascular impairment can be found (Wedi
and Kapp, 1999).
One of the more common associations in this study is recurrent dyspeptic oral ulcer. It was
detected in 9.6% of all patients. It was higher in Egyptian and Saudi than Kuwaiti patients but
not statistically significant. Recurrence rarely happened after eradication of H pylori in most
cases. A prospective, controlled clinical trial done in Otolaryngology Department of Tanta
University Hospitals, Tanta, Egypt; a total of 146 patients with recurrent multiple aphthous
ulcers of the oral cavity and pharynx and 20 normal control subjects were assigned to group 1 (n
= 58), in which the ulcers were strictly limited to the lymphoid tissues, or group 2 (n = 88), in
which the ulcers were randomly distributed in the oral cavity and pharynx. Helicobacter pylori
15. DNA was extracted from 3-mm-diameter tissue samples, and polymerase chain reaction
amplifications were performed for the 16S ribosomal RNA gene. In group 1, 39 patients (67%)
were positive for H pylori DNA, while in group 2, 9 patients (10%) were positive (P<.001). It
was not detected in any of the 20 control samples. It was concluded that these results support a
possible causative role for H pylori in recurrent aphthous ulcerations with a characteristic
distribution and affinity to mucosa-associated lymphoid tissues of the pharynx (Elsheikh and
Mahfouz, 2005). In 13 patients with Behcet’s disease, the number and size of oral and genital
ulcers diminished significantly and various clinical manifestations regressed after the eradication
of HP. It was concluded that HP may be involved in the pathogenesis of BD (Avci et al., 1999).
The presence and severity of GERD are more significant in Saudi and Kuwaiti than Egyptian
patients and in Saudi than Kuwaiti patients. The overall prevalence of GERD of all grades in
such population is (38.83%). The role of H pylori and its eradication in the aetiology or severity
of this disease remains unclear. Some cases improved after eradication; while others worsened.
However, most cases were not affected by eradication. Thus, it could be stated that neither the
presence of H pylori nor its eradication has any significant role in such disease. Therefore, the
presence of GERD by itself shouldn’t influence the decision of treatment of H pylori. The
appearance of new cases of GERD after eradication was not followed in this study. One study
showed that at 3 years, patients who had successful eradication of H. pylori had an incidence of
endoscopically proven esophagitis of 25% compared to patients who had ongoing infection who
had roughly half the rate of developing erosive esophagitis, 13% . In the same study, it was
found that only 3% of these patients actually had newly developed symptoms of GERD. In
another study, 250 patients with endoscopically documented duodenal ulcer disease underwent
rapid urease test and histology both before and 6 months after therapy. After 6 months, they
found only one patient with erosive esophagitis out of 242 (Nimish Vakil, 2001). However,
meta-analysis of 14 case-controlled studies and 10 clinical trials (after exclusion of the remaining
of 811 papers reviewed) showed significant association between absence of H. pylori infection
and GERD symptoms, and a positive association between anti-H. pylori therapy and occurrence
of both de novo and rebound/exacerbated GERD. The magnitude of this association was higher
for de novo GERD than for rebound/exacerbated GERD. The analyses performed cannot
exclude, however, that odds ratios from some larger studies may have in part inflated the
estimate of the pooled odds ratios, or that geographical or racial differences significantly interact
to influence the estimates (Cremonini et al., 2003). However, it was stated that patients with
peptic ulcer disease are more likely to benefit from anti-H. pylori therapy rather than risk the
development of GERD. Also, recent data showing prospectively the 8-year incidence of gastric
cancer in ulcer and non-ulcer patients creates a major argument in favour of H. pylori
eradication, given its carcinogenic potential (Uemura et al., 2001). At the other end of the
spectrum, H. pylori positive patients with minimal symptoms or dyspepsia rather than peptic
ulcer disease may receive more harm than benefit from eradication therapy. But still a
population-based dyspepsia trial has shown similar incidence of heartburn symptoms after
treatment in patients receiving eradication therapy and in those receiving placebo (Moayedi et
al., 2000).A prospective, double-blind study demonstrated, using excellent GERD quantifying
measures including validated symptom severity scores, endoscopy, and 24-h pH-metry, that there
exist no clinically significant differences in clinical or laboratory-related GERD manifestations
between H. pylori-infected and non-infected GERD patients (Fallone et al., 2004).
As regards cholecystitis in these patients, it was found that it was not higher than general
population with calcular cholecystitis present in 4.9% homogeneously in all groups. However, it
is recommended to study the presence of H pylori antigens or DNA in surgically removed
calcular gall bladder to certainly prove any association. No significant differences in the presence
16. of cholecystitis, whether calcular or non-calcular, between patient’s categories. Recent
epidemiologic results suggest a possible association between enterohepatic Helicobacter spp and
cholesterol cholelithiasis, chronic cholecystitis, and gallbladder cancer. More than 25
Helicobacter spp have been isolated from the stomach, intestinal tract, and liver of humans, other
mammals, and birds. Many of these organisms cause extragastric disease and several are able to
grow in bile, including Helicobacter hepaticus, Helicobacter bilis, and Helicobacter pullorum.
These nongastric (enterohepatic) Helicobacter spp generally colonize the distal small intestine,
cecum, and large intestine and subsequently the liver, where they have been implicated in, or
suggested to cause, hepatitis, hepatocellular carcinoma, cholecystitis, typhlocolitis, and colonic
adenocarcinoma (Maurer et al., 2005).
Diabetes mellitus was one of the most commonly associated disease detected in these
patients. It was found in 16.5% in all patients with the highest association (23%) found in Saudi
patients which is nearly equal to the prevalence in Saudi patients ~ 24% (Al-Nozha et al., 2004).
Diabetes mellitus is a common disease in the three nations studied. This percentage in such
young age group might be taken as an evidence of the close relation between the two diseases. It
was correlated directly and significantly with the presence of mouth ulcers (P = 0.002) and
atypical chest pain but not with any other autoimmune related manifestations such as ITP, AI
haemolytic anaemia, arthritis or skin rash. Many studies raised the issue of the association
between DM; particularly type 1 IDDM; and H pylori infection. In one study, Thirty-four IDDM
patients and 40 dyspeptic patients previously treated for H. pylori infection and successfully
eradicated (confirmed both by UBT and histology) were re-evaluated after 12 months. H. pylori
re-infection was significantly higher in IDDM patients compared to controls: (38% vs 5%
respectively, p<0.001). It was found also that, daily insulin requirement and glicated
haemoglobin were significantly higher in re-infected compared to uninfected patients (Ojetti et
al., 2001). Another study showed that H pylori infection, when present in participants with
halitosis, seems to predict a worse metabolic control than in H pylori-negative patients with
halitosis (Candelli et al., 2003). In another study, 429 patients with type 1 (n = 49) or type 2 (n =
380) diabetes mellitus and 170 nondiabetic controls were evaluated. Seroprevalence of H. pylori
was 33% and 32%, respectively, in patients with diabetes and controls (NS). It was concluded
that H. pylori infection appeared not to be associated with diabetes mellitus or upper GI
symptoms in diabetes mellitus (Xia et al., 2001). Other study (of 195 diabetic type I and II
patients and 216 blood donors) has shown a lower seroprevalence of H. pylori in diabetic
patients in comparison with the healthy population (27% vs. 51%, p < 0.001). Such finding
differs from the generally accepted experience of the higher sensitivity of these patients to
infection (Zenlenkova et al., 2002). The practical significance of these observations remains
unsolved. In our study, pancreatitis was found significantly more common in Saudi (7.5%) than
Egyptian (3.6%) and Kuwaiti (0%). Experimental study in rats showed that H pylori infection
increased the severity of ischemia-induced pancreatitis and aggravated disturbances in pancreatic
microcirculation in acute pancreatitis. It was found also to increase production of pro-inflammatory
IL-1beta (Warzecha et al. 2002).
The diseases with possible autoimmune pathogenesis were detected in low percentages in
these patients. These include, in addition to diabetes, isolated arthritis, autoimmune haemolytic
anaemia, ITP, Sjogren’s disease; arthritis and thyroid dysfunction; with arthritis being the most
common association (3.9%) with no differences between the three national groups. Thyroid
dysfunction was detected in 7.5% of all patients and equally divided between hpo- and
hyperthyroidism with no differences between the three groups of patients. The role for H. pylori
has also been postulated in other autoimmune diseases such as membranous nephropathy and
some acute immune polyneuropathies. The mechanisms behind these clinical observations still
17. remain unclear. Some studies showed that eradication of H. pylori infection may be effective in
the disappearance of autoimmune thrombocytopenia, Sjogren syndrome and Schonlein-Henoch
purpura. However, if confirmed, these findings could revise the diagnostic and therapeutic
approach to diseases previously considered as idiopathic (Gasbarrini and Franceschi, 1999). In
one study from Japan, H pylori infection was found to be involved in most ITP patients older
than 40 years, and it was recommended that eradication therapy should be the first line of
treatment in H pylori-positive ITP patients. In this study, complete remission and partial
remission rates were 23% and 42%, respectively, 12 months after eradication. In the majority of
responders, the platelet count response occurred 1 month after eradication therapy, and the
increased platelet count continued without ITP treatment for more than 12 months. H pylori
eradication therapy was effective even in refractory cases, which were unresponsive to
splenectomy (Fujimura et al., 2005). Similar findings were reported by other group also in Japan
(Hashino et al., 2003). The prevalence of H. pylori infection in patients with chronic autoimmune
hepatitis and controls was similar in one study of patients (Durazzo et al., 2002).
History of recurrent migraine, headache and vertigo was obtained in low percentage of cases,
but some of cases improved markedly after eradication therapy (migraine and vertigo showed
improvement in 11/26 and 19/49 respectively). This might be taken as evidence of the role of
chronic H pylori infection in the pathogenesis of these disorders. However, the percentages seen
in such disorders were not probably higher than general population.
Malignancies diagnosed in these patients included 7 oesophageal, 8 gastric adenocarcinoma,
8 gastric lymphoma, and 4 duodenal adenocarcinoma. All were advanced and managed in the
usual way of such tumors. It is now well recognized that chronic Helicobacter pylori infection is
a significant contributory factor in the development of gastric cancer, primarily in noncardiac
gastric cancer. An important meta-analysis published in 2001 reviewed 12 case-control studies in
which infection was determined by serology, demonstrating a relative risk of 5.9 for gastric
cancer outside the gastric cardia (Crowe 2005). More than 1500 Japanese subjects were followed
for a mean of 7.8 years. In those with H. pylori infection, the average rate of gastric cancer was
2.9% compared with 0% in those without infection. This observational study provides some of
the strongest evidence to date for the association of H. pylori infection with gastric cancer and,
interestingly, the highest risk was seen in infected subjects with nonulcer dyspepsia, in whom the
rate was 4.7%. As might be expected, no gastric cancers developed in infected subjects
presenting with duodenal ulcers, whereas the rate of gastric cancer for those presenting with
gastric ulcers was 3.4% (Uemura et al., 2001).Multivariate analyses in one study of gastric
adenocarcinoma, it was found that H pylori was an independent prognostic factor for relapse-free
survival and overall survival. Depth of tumour invasion, lymph-node metastasis, and patient age
67.5 years or older were also independent prognostic factors for overall survival (Meimarakis et
al., 2006). H. pylori infection is also associated with the development of lymphoma arising from
the mucosa-associated lymphoid tissue (MALT) of the stomach. Primary high-grade B-cell
gastric lymphoma in stages I(E) through II(E1) associated with H pylori may regress completely
after successful cure of the infection (Morgner et al., 2001). One case of gastric lymphoma of the
MALT type with a high-grade component was cured with disappearance of B-cell monoclonality
by Helicobacter pylori eradication alone (Miki et al., 2001). In another study, only half of the
patients showed disappearance of B-cell monoclonality while the remaining half showed
persistence of this monoclonality for several years (Thiede et al., 2001). Treatment of low-grade
gastric mucosa-associated lymphoid tissue lymphoma by eradication of Helicobacter pylori is
reported to result in complete lymphoma remission in approximately 75% of cases (Morgner et
al., 2001). In another study, H pylori and HCV were detected and localized in stomach in
association with chronic lymphocytic inflammatory response. Oligoclonal IgH gene
18. rearrangements were detected in three (from 60) patients who harboured both H. pylori and HCV
in their stomach and it was concluded that when both present, may favour the selection of clonal
B cells (Cammarota et al., 2002). Gastric carriage of Helicobacter pylori may play a role in the
development of exocrine pancreatic cancer (Stolzenberg-Solomon, 2001). In his study, he found
that subjects with H. pylori or CagA+ strains had a significantly higher risk of pancreatic cancer
than seronegative subjects, with odds ratios of 1.87 and 2.01, respectively. However, no cases of
pancreatic cancers were detected probably because of young age. Helicobacter pylori also can be
detected in liver tissue resected from patients with hepatocellular carcinoma. Conflicting reports
regarding the relationship between H. pylori and hepatocellular carcinoma were reported. This
means that it is uncertain whether H. pylori acts as a troublemaker, co-risk factor or innocent
bystander to the development of hepatocellular carcinoma. One study showed that H. pylori
seropositivity was more prevalent among patients with HCC (36/46, 78.2%) than in controls
(25/46, 54%) (P<0.05) ( Leone et al., 2003). In patients with HCV chronic liver disease, the
vacA sequence was amplified from 10 of 41(24%) samples (including 27% of those with HCC).
These data confirm the presence of H. pylori DNA sequences in human liver and suggest an
association of Helicobacter spp. with HCV-related chronic liver diseases. Further studies are
needed to ascertain which Helicobacter spp. infection plays a role in the development of HCC
(Dore et al., 2002). Also no cases of HCC were detected in this study.
No colon cancers detected in these patients. Also, colonoscopic examination was not done to
search for premalignant neoplasm. Patients who are seropositive for Helicobacter pylori are
more likely than seronegative patients to display colorectal neoplasia, according to a new report
by researchers in Japan. In one study of 332 Japanese patients who underwent routine high-resolution
colonoscopy and serologic testing for anti-H. pylori antibodies, it was found that 42%
of H. pylori-positive subjects had tubular adenomas of the colon compared with 19% of
seronegative patients (p < 0.0001). Similarly, the percentage of subjects with a totally normal
colonoscopic examination was lower in the H. pylori-positive group: 32% vs. 55% (p < 0.0005)
(Inui et al., 2005). Among patients infected with H. pylori, CagA+ seropositivity was found to be
associated with increased risk for both gastric and colonic cancer. Serum IgG antibodies against
H. pylori (ELISA) and CagA protein (Western blot assay) were tested in 67 patients with
colorectal adenocarcinoma, 36 with gastric adenocarcinoma, 47 with other malignancies (cancer
controls), and 45 hospitalized for transesophageal echocardiography (TEE controls). H. pylori
infection was noted in 50 colon cancer patients, 31 gastric cancer patients, 31 cancer controls,
and 32 TEE controls. In all, 41 (82%), 29 (94%), 11 (35%), and 13 (41%), respectively, of these
H. pylori-positive sera expressed CagA reactivity (p < 0.001 for all pairwise comparisons
between cases and controls) (Shmuely et al.,2001). However, more studies including prospective,
long-term examination of large groups of patients are needed to evaluate exactly the clinical
outcomes in the colon of H. pylori and its eradication, as well as to examine the biological basis
of H. pylori-associated neoplasia in the gastrointestinal tract.
ALT was found elevated in 28.7 % with more affection in Saudi, then Kuwaiti than Egyptian
patients but not statistically significant. Elevation of ALT in these patients had no explanation
from the history, examination and viral study. However, many patients have fatty liver by
ultrasound and non-alcoholic fatty liver disease was suspected but not thoroughly evaluated.
However, statistically, highly significant decrease in ALT level (P < 0.001) was found in all
patients after eradication of infection when analyzed altogether and as separate groups. Thus, H
pylori may at least partially participate in elevation of this liver enzyme. In patients with HCV
chronic liver disease, the vacA sequence was amplified from 10 of 41(24%) samples (including
27% of those with HCC). These data confirm the presence of H. pylori DNA sequences in human
liver and suggest an association of Helicobacter spp. with HCV-related chronic liver diseases
19. (Dore et al., 2002). In another study, it was found that 70.2% (33/47) of cirrhotic patients and
47.5% (28/59) of noncirrhotic patients were H. pylori-positive (Queiroz et al., 2006). H. pylori
infection is associated to an impairment of cytochrome P-450 liver metabolic activity (Giannini et
al., 2003). Patients with chronic liver diseases, except autoimmune hepatitis patients, showed
increased antibody levels to other Helicobacter spp. Such as H. bilis/H. hepaticus compared with
the population and blood donors indicating a possible role of enteric Helicobacter in the natural
course of chronic liver diseases (Vorobjova et al., 2006).
Regarding the diagnostic tests of H pylori, no differences between the three patient categories
in the positivity of different tests. The most sensitive test was the microscopic examination of
gastric biopsies which is statistically more positive than all other tests except rapid urease test.
Rapid urease test on gastric biopsies is found more significantly positive than breath test and
serology in all patients and different categories. Cag A positivity correlated only with breath test
and presence of autoimmune haemolysis, but not with any other digestive or systemic
manifestations in these patients. It was stated that infection with a more virulent H pylori strain
was associated with a higher degree of antral and body colonisation grade, inflammation, and
activity (Cover, 1996 and Kim et al., 2001). Although certain H. pylori strains are associated
with pathological outcomes, the specific mechanisms that lead to these relationships have not
been fully delineated. Cag A positive bacteria is associated with an augmented risk for ulcer
disease and distal gastric cancer (Censini, S. et al.1996). However, the gastric inflammatory
reaction induced by H pylori does not depend on a single factor, but probably results from the
synergistic effect of multiple virulence factors, which work together in a complex way, causing
damage to the host (Zambon et al., 2003).
Conclusion:
It is concluded from this study that H pylori infection is present in most Arabian countries nearly
with similar, but of somewhat variable extent, manifestations wither digestive or extradigestive.
The associated extradigestive manifestations described cannot be attributed to H pylori in all
cases, but it is recommended to screen for this infection and eradicate it particularly if there are
additional upper GIT complaints. The presence of GERD should not affect the decision of
treatment of this infection, even if it is suspected that some cases may have exaggeration of their
symptoms. Also, chronic gastric inflammation due to virulent H pylori infection may have some
sort of hepatotoxic effect for which eradication of this organism must be considered. Finally,
diagnosis and treatment of H pylori might be considered in the workup in the management of
diseases with autoimmune pathogenesis such as ITP, autoimmune haemolytic anaemia, skin
diseases, thyroid dysfunction, diabetes mellitus, and others.
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24. الباكتريا الحلزونية البوابية: المجال الكلينيكى والمرراض ذات الصلة فى دراسة مرقارنة
فى ثلث أقطار عربية
شندى محمد شندى شريف* و نعيمة العشرى**.
* قسمى المراض المتوطنة والكبد والجهاز الهضمى و** الكيمياء الكللينيكية معهد تيودور بحلهارس للبححاث
تعتبر البكتريا الحلزونية البوابية مرن أكثر المرراض انتششارا فشى العشالم. وقششد ثبششت أنهشا المسشبب الرئيسشى لمرششراض المعششدة
كالقرح واللتهاب المعدى المزمرن و أورام المعدة, وأنه قد يكون لها علقة بأمرراض أخرى مرثل أمرراض الجلد والقلششب و الوعيششة
الدمروية و المناعة وأورام الغدد اللمفاوية وفقر الدم وبطئ النمو فى الطففال. وكان الهدف مرن هذا البحث هو دراسة و تقييم دور
هذا الميكروب فى ظهور العراض الهضمية والغير هضمية للمرضي المترددين على عيادات الجهاز الهضشمى فشي بعشض الششدول
العربية. و قد أجرى هذا البحث على ٦٢٣ مرريض بهذا الميكروب و هم ٢٢٥ مرن مرصر و ١٨٨ مرن الكششويت و ٢١٠ مرششن المملكشة
العربية السعودية. وقد تم أخذ التاريخ المرضى وفحص المرضى وعمل الفحوص التقليدية و الخاصة بالميكروب ومرنظار المعششدة
و الفحص النسيجي لجميع المرضى. وتم مرتابعة الحالت بعد العلج لبيان تأثيره على هذه العراض.
وقد أوضحت النتائج أن حالت الصابة المتكررة كانت أكثر انتشارا في المرضى السعوديين وكانت مرصحوبة بمعدل أكثر في
خلل وظائف الغدة الدرقية والتهاب البنكرياس. :مرا وجد لن أمرراض قرح الفم والدوار والسكري و زوائد المعدة و نقششص الحديششد
بالدم كانت أكثر حدوثا فى المرضشى المصشريين عشن غيرهشم. وأن المرسشاك المزمرشن و ألم الصشدر وخلشل وظشائف الغشدة الدرقيشة
والتهاب البنكرياس و ارتفاع إنزيمات الكبد كانت أكثر حدوثا فى المرضى السعوديين عن غيرهم. و أن ارتششداد المعشدي المشرئ و
الدوار كانشا أكشثر حششدوثا فشى المرضشى السشعوديين و الكويشتيين عششن المصششريين. و كشان السشكري مرششن أكشثر المرششراض ششيوعا (
١٦٠٥ %) و تزامرنا فى هٶلء المرضى ويتبعه المرساك المزمرن ( ١١٠٩ %) و الذى كان مررتبطا ارتباطفا مرباشششرا بشششدة التهششاب
Cag " المعدة. وكانت قرحة الثنى عشر أكثر حدوثا فى المرضى صغار السن. وكان المرض الوحيد المرتبط بايجابية "الكاج أ
هو فقر الدم التكسرى الناتج عن اضطراب المناعة الذاتية . وكان التهاب البنكرياس مررتبطشا ارتباطفشا مرباششرا بوجشود إصشابة A
مرتكررة و القرح المعدية و أورام الجهاز الهضمى و انسداد مرخرج المعدة والتهاب المفاصل و الطفح الجلدي. وقد كان فقششر الششدم
ونقص الحديد أكثر شيوعا مرع تقرحات المعدة والثنى عشر و مرع أورام الجهاز الهضمى.
٣٨ ) و / أمرا بعد العلج والقضاء على الميكروب فقد كان هناك تحسشنا كشبيرا أثنشاء المتابعشة فشى حشالت الطفششح الجلششدى( ٢٨
١٩⁄ ١١ ) والششدوار ( ٩ ⁄ ٥١ ) و تحسنا بسيطا و مرتوسطا فشى الصششداع النصششفى ( ٢٨ ⁄ ٣٧ ) والمرساك المزمرن ( ٧٣ ⁄ قرحة الفم ( ٥٩
٤). و كان هناك زيادة عالية الدللة فى مرعدل الحديد والهيموجلوبين فى جميع الحالت.
وكان أدق التحاليل للكشف عن هذا الميكروب هو الكشف الميكروسكوبى ثم اختبار اليورياز السريع لعينة نسيج المعدة.
يستنتج مرن هذا البحث أن الهيلكوباكتر البوابية هى عدوى شائعة بشكل عام فشى هششذه البلششدان العربيشة مرشع تششابة كشبير فشي
العراض الهضمي و الغير هضمية و لكن يوجد اختلفات بسيطة كما أن العراض الغيششر الهضششمية فشى بعشض الحشالت لششم تكششن
مررتبطة بوجود البكتريا. ومرع ذلك فانه ينصح بعمل التحليل في هذه الحالت والعلج للحالت اليجابيشة مرنهشا وخاصشة فشي وجشود
أعراض التهابات الجهاز الهضمى العلوى أو أمرراض اضطرا بات المناعة الذاتية
