Non-ulcer Dyspepsia Patients Research Articles

Stress, coping, and depression in non-ulcer dyspepsia patients

Thirty adults with upper gastrointestinal symptoms in the absence of structural organic disease diagnosed with non-ulcer dyspepsia (NUD) were compared to 30 healthy adults who had visited the hepatobiliary clinic for medical evaluation of non-organic complaints without NUD. Medical investigation in both groups were negative. Before independent gastrointestinal physicians conducted diagnostic evaluations, all subjects were evaluated for anxiety and depressive symptoms, stressful life events, coping style, and social support. The measures included Symptom Checklist 90-Revised (SCL-90-R), Beck Depression Inventory (BDI), Spielberger State–Trait Anxiety Inventory (STAI), Ways of Coping Checklist, and Interpersonal Support Evaluation List, and a self-report questionnaire, which measured the quantity of perceived stressful life events. The NUD patients reported significantly more symptoms of depression, more perceived stressful life events, less problem-focused coping, and less social support than the control subjects. Depressive symptoms were negatively correlated with interpersonal support, whereas, problem-focused coping was positively correlated with interpersonal support in the NUD patients. The two groups did not differ significantly in terms of anxiety and emotion-focused coping. The implications of these findings for the diagnosis and treatment of NUD are discussed.

Clinical and Histologic Predictors of Helicobacter pylori Infection Recurrence

Factors influencing Helicobacter pylori infection recurrence still have not been fully clarified. The aim of this study was to determine whether, after eradication of H. pylori, any clinical or histologic features could yield information on infection relapse. We enrolled in the study 72 patients successfully treated for H. pylori infection by either dual (n = 49) or triple (n = 23) therapy. H. pylori eradication was defined as a negative bacterial finding by rapid urease test and histologic assessment at least 4 weeks after cessation of therapy. Upon eradication, gastritis grading was performed and patients were asked to return for an endoscopic control 6-8 months later. The recurrence of H. pylori infection was observed in 12 of 72 (16.7%) patients. The infection recurrence rate resulted significantly higher in nonulcer dyspepsia patients (p = 0.01 ) and in women (p = 0.03), whereas infection relapse did not differ between patients treated with dual or triple therapy. There was a strong (p = 0.0001 ) relationship between the persistence of chronic active gastritis after H. pylori eradication and recurrence of infection, whereas gastritis grade and metaplasia were not related to recurrence. In conclusion, this study found that H. pylori infection recurrence after successful dual or triple therapy is fairly high and that gastroduodenal disease, gender, and gastritis activity seem to affect infection relapse.

H pylori and Lewis antigens

See article on page 18 Lipopolysaccharide (LPS) of many Helicobacter pylori strains expresses Lewis antigens (Lex, Ley, Lea, Leb) which are similar to those expressed by gastric epithelial cells (“molecular...

Antibody response to Helicobacter pylori CagA and heat-shock proteins in determining the risk of gastric cancer development

Objective. To investigate whether the systemic antibody response to Helicobacter pylori heat shock protein B can be considered, in addition to anti cytotoxin-associated protein (CagA) antibody determination, a further serological marker of increased risk of gastric cancer development. Methods. A total of 98 Giemsa positive Helicobacter pylori patients (28 with gastric cancer, 30 with duodenal ulcer and 40 with non-ulcer dyspepsia) were studied. Serum samples obtained from all patients were tested for IgG antibodies to CagA (116 kDa), VacA (89kDa) and heat skock protein B (54 kDa) antigens of Helicobacter pylori by the Western blot technique. Results. 26 28 patients (92.9%) with gastric carcinoma, 29 30 patients (96.7%) with duodenal ulcer and 30 40 patients (75.0%) with non-ulcer dyspepsia were seropositive for CagA protein. The prevalence of serum IgG antibody to CagA in the cancer patients was not significantly higher than in duodenal ulcer and non-ulcer dyspepsia patients. The prevalence of antibodies to VacA was not significantly different between gastric carcinoma and non-ulcer dyspepsia patients. In contrast the prevalence of systemic antibodies to heat skock protein B was significantly higher in gastric cancer patients (78.6%) than in duodenal ulcer (36.7%, p=0.002) or non-ulcer dyspepsia patients (52.5%, p=0.029). Conclusions. The detection of antibodies to heat shock protein B is proposed as an additional test which, in association with the determination of serum antibodies to CagA, could help in determining the risk of developing severe gastroduodenal disease, and gastric cancer, in particular.

Salivary and gastric epidermal growth factor in patients with Zollinger-Ellison syndrome: its protective potential.

Evidence is accumulating that epidermal growth factor (EGF) is a major molecule contributing to the maintenance of the integrity of the upper alimentary tract mucosa before and after injury by acid and pepsin. Patients with Zollinger-Ellison Syndrome (ZES) typically have hypersecretion of acid and pepsin; however, the concentration and rate of secretion of salivary and gastric EGF that could counteract these potentially aggressive factors are unknown. Accordingly, this study was conducted to determine whether EGF affords mucosal protection in ZES patients. The concentration and output of salivary (sEGF) and gastric epidermal growth factor (gEGF) were measured in eight patients with ZES and the results compared to those in 17 patients with nonulcer dyspepsia (NUD), serving as a control group. All patients had normal esophageal and gastric mucosa as determined by endoscopy. Total saliva was collected during 1-h parafilm- and 1-h pentagastrin/parafilm-stimulated conditions, as well as basal and pentagastrin-stimulated gastric juice. The concentration and output of EGF were determined by radioimmunoassay. The concentration of EGF in saliva collected from ZES patients after parafilm chewing was significantly higher compared to that in NUD patients (4.61 +/- 0.59 vs 2.75 +/- 0.50 ng/ml, p < 0.05). The concentration of EGF in saliva collected after pentagastrin stimulation in ZES patients was also significantly higher than in NUD patients (4.37 +/- 0.73 vs 2.22 +/- 0.37 ng/ml, p < 0.05). Salivary EGF output during parafilm chewing in ZES and NUD were similar (68 +/- 6.4 vs 109 +/- 25.2 ng/h). Salivary EGF output after administration of pentagastrin in ZES and NUD was also similar (66 +/- 6.1 vs 132 +/- 45.4 ng/h). Basal EGF output in the gastric juice of patients with ZES was 3-fold higher than in patients with NUD (801 +/- 73 vs 271 +/- 32 ng/h, p < 0.01). Pentagastrin-stimulated EGF output was similar in both groups (705 +/- 92 vs 675 +/- 168 ng/h). Patients with ZES have a significantly higher EGF concentration in saliva and EGF output in basal gastric juice. This elevated content of salivary and gastric EGF in ZES patients may play a protective role in preventing the development of reflux esophagitis and gastric ulcer under the impact of gastric acid and pepsin hypersecretion.

Salivary and gastric epidermal growth factor in patients with Zollinger-Ellison syndrome: its protective potential

OBJECTIVE: Evidence is accumulating that epidermal growth factor (EGF) is a major molecule contributing to the maintenance of the integrity of the upper alimentary tract mucosa before and after injury by acid and pepsin. Patients with Zollinger-Ellison Syndrome (ZES) typically have hypersecretion of acid and pepsin; however, the concentration and rate of secretion of salivary and gastric EGF that could counteract these potentially aggressive factors are unknown. Accordingly, this study was conducted to determine whether EGF affords mucosal protection in ZES patients. METHODS: The concentration and output of salivary (sEGF) and gastric epidermal growth factor (gEGF) were measured in eight patients with ZES and the results compared to those in 17 patients with nonulcer dyspepsia (NUD), serving as a control group. All patients had normal esophageal and gastric mucosa as determined by endoscopy. Total saliva was collected during 1-h parafilm- and 1-h pentagastrin/parafilm-stimulated conditions, as well as basal and pentagastrin-stimulated gastric juice. The concentration and output of EGF were determined by radioimmunoassay. RESULTS: The concentration of EGF in saliva collected from ZES patients after parafilm chewing was significantly higher compared to that in NUD patients (4.61 ± 0.59 vs 2.75 ± 0.50 ng/ml, p < 0.05). The concentration of EGF in saliva collected after pentagastrin stimulation in ZES patients was also significantly higher than in NUD patients (4.37 ± 0.73 vs 2.22 ± 0.37 ng/ml, p < 0.05). Salivary EGF output during parafilm chewing in ZES and NUD were similar (68 ± 6.4 vs 109 ± 25.2 ng/h). Salivary EGF output after administration of pentagastrin in ZES and NUD was also similar (66 ± 6.1 vs 132 ± 45.4 ng/h). Basal EGF output in the gastric juice of patients with ZES was 3-fold higher than in patients with NUD (801 ± 73 vs 271 ± 32 ng/h, p < 0.01). Pentagastrin-stimulated EGF output was similar in both groups (705 ± 92 vs 675 ± 168 ng/h). CONCLUSIONS: Patients with ZES have a significantly higher EGF concentration in saliva and EGF output in basal gastric juice. This elevated content of salivary and gastric EGF in ZES patients may play a protective role in preventing the development of reflux esophagitis and gastric ulcer under the impact of gastric acid and pepsin hypersecretion.

The cag pathogenicity island in Helicobacter pylori is not essential for interleukin-12 induction in monocytes

Methods: Twelve patients with active duodenal ulcer (DU), and 10 patients with non-ulcer dyspepsia (NUD) were enrolled upon detection of H. pylori infection at endoscopy. Seven matched dyspeptic patients with normal endoscopic and histological findings were also enrolled as controls. Biopsy specimens were utilised for H. pylori and histological assessments, and for antral lymphocytes density assessment by an histomorphometric method. A blood sample was obtained from each patient to determine basal gastrin levels. All patients were controlled 4 weeks after concluding H. pylori treatment by a further endoscopy. Results: DU and NUD patients had both antral lymphocyte density (5464 ± 1328 and 5635 ± 1186 vs 2267 ± 557 lymphocytes/mm2; p <0.001 and p <O.OOI,respectively) and gastrin levels (66.7 ± 14.1 and 60.4 ± 21.7 vs 40.7 ± 7.8 pg/dl; p = 0.004 and p = 0.02, respectively) higher than controls, while no significant differences emerged between DU and NUD patients. There was a significant direct correlation between antral lymphocyte density and gastrin levels both in DU (r = 0.77; P = 0.003) and in NUD (r = 0.75; p = 0.03) patients, while no correlation was found in control subjects (r = 0.12; p = 0.8). After treatment, this correlation persisted in eradication failure patients (r = 0.68; p = 0.027), while disappearing in successfully cured patients.

Helicobacter pylori(HP) eradication in non-ulcer dyspepsia (NUD): A randomized, double-blind, place-bo-controlled study with a 12-month follow-up

The relationships between Hp infection and NUD are uncertain. Consequently, the clinical benefit of the eradication remains controversial. The aim of this multicenter, randomized, double-blind, placebo-controlled study was to determine the effect of Hp eradication on symptoms of dyspepsia 12 months after treatment. Methods: 253 patients with severe ulcer-like pain (grade 3 or 4 on Likert scale: from 0= none to 4= very severe) for at least 3 months, Hp infection (Clo-Testregistered with histological confirmation) and no evidence of peptic ulcer or esophagitis on upper GI endoscopy were treated. Patients were randomly allocated to a 7-day treatment of ranitidine 3OOmgx2, amoxicilline Igx2, clarithromycine 5OOmgx2 (RAe) or placebo (PLA) and were followed-up for 12 months (day 8 and months 3, 6, 9 and 12). Treatment success was defined as the reduction of at least 2 grades on Likert scale between randomization and the 12-month visit. Complete resolution of dyspeptic symptoms was defined as grade 0 on Likert scale. Presence of Hp was assessed at 3 months by l3C-urea breath-test and at 12 months by histology. Gastritis was histologically graded (Sydney System) on 2 antral and 2 corpus biopsies performed at randomization and at 12 months by an expert gastrointestinal pathologist blinded to treatment group. Results: The 2 groups were comparable. Hp eradication rates at 3 months were 70% in RAC and 9% in PLA group, and at 12 months 69% and 18% respectively. By intention to treat there was no significant difference at 12 months between the 2 groups in treatment success rates (62% RAC and 60% PLA). However, complete symptom resolution was significantly more frequent (p<0.05) in RAC group (43%) than in PLA group (31%). In RAC group, treatment success rates were 84% among patients with Hp eradication and 64% among patients with persistent infection at 12 months (p=O.04). Chronic gastritis persisted in 91% of patients in RAC group and 89% of patients in PLA group after 12 months. However, histological scores for inflammation, activity and lymphoid infiltration were significantly higher in PLA group than in RAC group. Scores for atrophy and metaplasia were similar in the 2 groups. Conclusion: Curing Hp infection in NUD patients is more likely associated with complete symptom relief at 12 months despite the large placebo effect in reducing dyspeptic symptoms severity. Moreover, chronic gastritis persisted with improvement of inflammation and activity 1 year after Hp eradication treatment.

Is there a difference in eradication rate of helicobacter pylori between peptic ulcer patients and non-ulcer dyspepsia patients? A survey of 1666 patients

Is there a difference in eradication rate of helicobacter pylori between peptic ulcer patients and non-ulcer dyspepsia patients? A survey of 1666 patients

Gastric accommodation measured noninvasively in post-fundoplication and nonulcer dyspepsia patients

Gastric accommodation measured noninvasively in post-fundoplication and nonulcer dyspepsia patients

The incidence of reflux oesophagitis after cure of Helicobacter pylori in a Japanese population.

To investigate the incidence of reflux oesophagitis after antibacterial therapy for Helicobacter pylori infection in our patient population. Subjects were 451 H. pylori-infected patients (primary symptom: peptic ulcer disease in 347, nonulcer dyspepsia in 100, and reflux oesophagitis in four): 11 of these patients had reflux oesophagitis on study entry. H. pylori infection was treated by a proton pump inhibitor/amoxycillin-clarithromycin regimen for either 7 or 14 days. Each patient was examined by endoscopy before treatment and more than 6 months after treatment to compare oesophageal findings. In addition, 227 patients were interviewed regarding reflux symptoms, using symptom questionnaires, before and more than 6 months after treatment. Among 440 patients who did not have reflux oesophagitis prior to antibacterial treatment (340 peptic ulcer patients and 100 nonulcer dyspepsia patients), 23 patients whose infection was eradicated developed reflux oesophagitis (5.4%). The 11 patients who had reflux oesophagitis prior to treatment were all successfully cured of infection. Six of these patients showed no change in their oesophagitis, while the condition improved in three and worsened in two. Symptom scores improved in 34 of the 36 patients who reported reflux symptoms. Among 19 patients who showed persistent infection, only one developed reflux oesophagitis (5.2%), while none complained of newly developed symptoms following treatment. Development of reflux oesophagitis after treatment of H. pylori infection was observed in a Japanese population. However, the incidence of this condition was comparable between those with persistent H. pylori infection and those in whom the infection was eradicated.

The effect of Helicobacter pylori eradication therapy on gastric antral myoelectrical activity and gastric emptying in patients with non-ulcer dyspepsia.

Dysmotility of the gastroduodenal region and delayed gastric emptying have been considered to play roles in non-ulcer dyspepsia (NUD). Helicobacter pylori-induced inflammation of the gastric mucosa may affect gastric motility. To evaluate the effects of H. pylori eradication therapy on gastrointestinal motility and symptoms in NUD patients. : Forty-six NUD patients were examined for gastric emptying, antral myoelectrical activity, H. pylori infection, and symptom scores. In H. pylori-positive NUD patients, gastric emptying, antral myoelectrical activity, and symptom scores were also analysed 2 months after cure of H. pylori infection. Sixty-seven per cent of NUD patients were H. pylori-positive. Both abnormal gastric emptying and antral myoelectrical activity were observed in NUD patients. H. pylori-positive NUD patients were divided into three groups according to their gastric emptying: the delayed group, the normal group, and the rapid group. In the delayed and rapid gastric emptying groups, the emptying and symptom scores were improved significantly by eradication. There was no improvement in symptom scores in the normal gastric emptying NUD group by the eradication therapy. Disturbed gastric emptying and antral myoelectrical activity play roles in NUD. H. pylori-induced disturbed gastric emptying may cause some NUD symptoms. Gastric emptying and symptom scores are improved by H. pylori eradication therapy in NUD patients with disturbed gastric emptying; H. pylori eradication therapy is effective in H. pylori-positive NUD patients with disturbed gastric emptying.

Effects of Tropisetron, a 5-HT3 Receptor Antagonist, on Proximal Gastric Motor and Sensory Function in Nonulcer Dyspepsia

Background: Visceral hypersensitivity is claimed to be involved in the pathogenesis of nonulcer dyspepsia (NUD). In a double-blind crossover study, we evaluated the effects of tropisetron, a 5-HT₃ receptor antagonist, on gastric accommodation, reflex relaxation, and sensitivity in NUD patients. Methods: Eight patients and 10 healthy controls received placebo or 5 mg tropisetron on separate days. On each day, gastric accommodation and relaxation were investigated using a gastric barostat. The perception during gastric distension and relaxation was scored by a verbal perception score. Results: Under both medications, gastric accommodation and postprandial gastric reflex relaxation were not impaired in the NUD patients. The visceral perception was increased in the NUD patients and not substantially influenced by tropisetron. Conclusions: Tropisetron does not influence gastric accommodation, reflex relaxation, or gastric sensitivity in NUD patients and healthy controls.

Serological response to Helicobacter pylori recombinant antigens in Chilean infected patients with duodenal ulcer, non‐ulcer dyspepsia and gastric cancer

We have previously cloned 10 Helicobacter pylori antigen genes from a Chilean strain including: cytotoxin VacA, a truncated region of CagA (called A17), a species-specific protein (Ag26), urease subunits (UreA, UreB), a flagellin, (FlaB), heat shock proteins (HspA and HspB), an adhesin (HpaA) and a lipoprotein (Lpp20). Immunogenicity of these antigens was tested by immunoblot with sera of Chilean infected patients, revealing that HpaA, A17, HspB and VacA were more frequently recognized (86%, 82%, 68% and 68%, respectively). According to the clinical condition, it was determined that Lpp20 was preferentially recognized by sera from non-ulcer dyspepsia patients (80%), A17 and VacA by patients with duodenal ulcer (92% and 83% respectively), and HspB by patients with duodenal ulcer (83%) and gastric cancer (90%). An ELISA was developed with a purified mixture of A17 and VacA antigens to test the different groups of patients. It was found that sera from duodenal ulcer patients showed higher values than those from non-ulcer dyspepsia patients, but this difference was not significant (p<0.2). Moreover, sera from gastric cancer patients showed values lower than those from non-ulcer dyspepsia patients (p<0.019). These results indicate that, in the Chilean population, antibodies raised against VacA and A 7 are not markers either for duodenal ulcer or for gastric cancer.

Problems in measurement of quality of life in dyspepsia trials.

In this review methodological problems in the measurement of quality of life in non-ulcer dyspepsia (NUD) patients are discussed. To date very few validated outcome measures are available for NUD-trials. It is unclear whether non GI-related symptoms need to be measured by these instruments in addition to GI-symptoms. Another important issue is how overlap with patients who suffer from gastro-esophageal reflux disease can be avoided.

6 Role of gastric acid in the aetiology of dyspeptic disease and dyspepsia

The main diseases associated with dyspepsia are peptic ulcer disease, gastro-oesophageal reflux disease and non-ulcer dyspepsia. Increased gastric acid secretion is a characteristic of most duodenal ulcer patients and of a small minority of non-ulcer dyspepsia and gastro-oesophageal reflux disease patients. Although acid secretion is normal in most gastro-oesophageal reflux disease patients, the condition is mainly the result of excess exposure of the distal oesophagus to acid refluxing from the stomach. Increased mucosal sensitivity to acid is involved in the aetiology of dyspeptic symptoms in the majority of patients with peptic ulcer disease and gastro-oesophageal reflux disease, and in a minority of non-ulcer dyspepsia subjects. Gastric acid, therefore, plays an important role in both the aetiology of dyspeptic diseases and in the aetiology of dyspeptic symptoms.

Detection and characterization of Helicobacter pylori from patients with gastroduodenal diseases

Polymerase chain reaction and cytotoxin assays were performed to identify as Helicobacter pylori type I ( cagA +/tox +) or type II ( cagA −/tox −) 56 (59.6%) strains from 94 patients. Of these patients 64 were affected by nonulcer dyspepsia (NUD), 10 by gastric ulcer (GU), 19 by duodenal ulcer (DU), and 1 by both GU and DU. H. pylori strains were tested for cagA using two sets of primers; target sequences were detected in 40–42/56 (71.4–75%) depending on the set of primers used, while cytotoxin-producing strains (tox+) were 26/56 (46.4%). Tox + strains were isolated in 13/32 (40.6%), 2/7 (28.6%), and 11/17 (64.7%) in NUD, GU, and DU patients, respectively. However, the different percentage between cagA + strains from NUD patients (13/32; 40.6%) and patients with ulcerative diseases (13/23; 54.2%) is not statistically significant ( p = 0.462). Because the two sets of primers employed for amplification of cagA target sequences give different results, we concluded that cagA alone could not be taken as predictive factor for severity of gastroduodenal disease. It has been found that H. pylori type I is associated with duodenal ulcer disease.

Does serology testing for H. pylori infections make sense for community-based physicians?

We investigated whether the serological assessment of H. pylori (Hp) infections is an accurate diagnostic tool for general practitioners, which meaning Cag A and Vac A antibodies (AB) have in patients with ulcer disease (UD) or non ulcer dyspepsia (NUD), whether assessment of these mentioned AB can explain the highly significant ethnical differences regarding LID and whether there are other serological laboratory parameters correlating with Hp infections (e.g. BSR, RBC, WBC, CRP, electrophoresis, further Hp-specific ABs). Hp-status was assessed by endoscopy (urease-test, histology) and compared to serological parameters (Hp-CFR; Hp-immunoblot (Mikrogen) IgG / IgA; AB against CagA, VacA, Urease A + B and further Hp-specific antigens). 122 patients were investigated, n=86 were Hp-infected and untreated, n=36 were Hp-negative following successful eradication therapy with a new triplescheme (for six days: 500 mg azithromycin od + 2000 mg tinidazole od + 40 mg pantoprazole hid): 1) In 58 % of the successfully Hp-eradicated patients highly positive serological Hp-tests could be found even 1 18 months following triple-therapy; in 21% of all successfully treated patients therapy was 12 18 months ago. 2) In untreated patients together both AB against CagA + VacA tended to be positive more frequent in patients with UD (45.5% CagA + VacA positive) than with NUD (25.0% CagA + VacA positive). 3) The 3-fold higher ulcer rate in Turkish patients at 30.3 % of all Hp-infected patients with upper abdominal complaints could not be sufficiently clarified by means of serology (CagA+VacA together positive in 47.0% of Turkish versus 28.5% in European patients). 4) In 9% of all Hp-infected NUD and UD patients no CagA -, as well as no VacA AB Could be shown. 5) In 4% of all Hp-infected patients no CagA-AB could be found despite VacApositivity. 6) Neither in Hp-infected nor in successfully treated patients a correlation could be found regarding Hp-status and other serological above mentioned laboratory parameters. Also, the determination of Hp-CFR, of AB against urease A + B and further Hp-specific antigens had no meaning for the assessment of the inflammatory process and the severity of disease, Our data show, that Hp-serology testing is of low value for community based physicians, because serological results neither yield a certain evidence of the existence of an acute Hp-infection nor for the pathogenicity of H. pylori or the severity of the disease caused by these bacteria.

Serologic detection of CagA positive Helicobacter pylori infection in a northern Italian population: its association with peptic ulcer disease.

About 60-70% of Helicobacter pylori strains possess cagA (cytotoxin associated gene A) gene and express its product CagA, a highly immunogenic 128-140 kD protein. Patients infected with CagA positive strains develop serum IgG anti-CagA. A serologic response to CagA has been detected in Helicobacter pylori infected patients with peptic ulcer more frequently than in those with gastritis alone. It is nuclear whether this finding is consistent in different geographical populations. We investigated the relationship between anti-CagA seropositivity and peptic ulcer disease in a Northern Italian population. We studied 135 H. pylori infected patients: 65 with duodenal ulcer (DU), 28 with gastric ulcer (GU) and 42 with non ulcer dyspepsia (NUD). Sera from these patients were assayed by EIA (enzyme immunoassay) for anti-CagA IgG. A high prevalence of anti-CagA was found associated with DU (86.1%) and GU (96.4%), while NUD patients showed anti-CagA seropositivity of 52.4% (Odd ratio, 5.66; 95% confidence interval, 2.23 to 14.32; p < .001, DU vs. NUD; Odd ratio, 24.5; 95% confidence interval, 3.05 to 197.6; p = .003, GU vs. NUD). DU patients showed anti-CagA seropositivity titer (1.15 (0.61 OD, mean (SD) higher than that of NUD patients (0.78 (0.60 OD, mean (SD) (p < .05). These data demonstrate in a Northern Italian population that anti-CagA seropositivity is strongly associated with peptic ulcer disease and suggest that CagA might play an important role in ulcer pathogenesis.

Analysis of the expression of CagA and VacA and the vacuolating activity in 167 isolates from patients with either peptic ulcers or non-ulcer dyspepsia

Objectives: The goals of this study were: 1) to examine the prevalence of cytotoxin-associated protein (CagA), vacuolating cytotoxin (VacA), and the vacuolating cytotoxin activity (VCA) in vitro of infecting Helicobacter pylori isolates and 2) to clarify the relation between the expression of these virulence factors and the occurrence of peptic ulceration. Methods: One hundred sixty-seven clinical isolates of H. pylori from patients with peptic ulcer disease (gastric ulcer, 62 cases; duodenal ulcer, 48 cases) and nonulcer dyspepsia (57 cases) were studied regarding their genetic and phenotypic properties. Results: Type 1 bacteria, which had both CagA and VCA, and type 2 bacteria, which did not express either CagA or VCA, represented 62.9% and 7.8%, respectively; the remaining 29.4% had an intermediate phenotype, expressing either CagA independent of the presence of VCA (CagA +VCA −) or vice versa (CagA −VCA +). CagA +VCA − and CagA −VCA + bacteria represented 17.4% and 12.0%, respectively, both of which were more numerous than the type 2 category. The proportion of the CagA-positive isolates was significantly higher in both the duodenal ulcer (97.9%) and gastric ulcer (83.9%) patients than in the non-ulcer dyspepsia patients (61.4%) ( p < 0.01). On the other hand, the proportion of the VacA/VCA-positive isolates was not significantly different between peptic ulcer disease and non-ulcer dyspepsia. Conclusions: The currently used classification of this bacterium based on the concomitant expression of CagA and VacA/VCA into the two major types is not adequate. The CagA-positive phenotype thus may be important as a virulence marker for peptic ulcer disease independent of the presence of VacA/VCA.