Herpes simplex virus types 1 and 2 and cytomegalovirus in peptic ulcer disease and non-ulcer dyspepsia.

The prevalence and the serum levels of IgG antibody to Herpes simplex virus type 1 or 2 (HSV1, HSV2) and to cytomegalovirus (CMV) were studied by ELISA in patients with active peptic ulcer -- duodenal and gastric -- and non-ulcer dyspepsia. Two hundred and forty-two consecutive patients with endoscopically confirmed active peptide ulcer -- 170 duodenal ulcers, 72 gastric ulcers -- and 95 consecutive patients who fulfilled the criteria for the diagnosis of non-ulcer dyspepsia were included in the study. The patients, aged 17-80 years, were well matched for age and sex. Antibody to cytomegalovirus was found in 83% of duodenal ulcer, 85% of gastric ulcer and 75% of non-ulcer dyspepsia patients; differences were not significant. The prevalence of HSV1 antibody was significantly higher in patients with duodenal ulcer than in those with non-ulcer dyspepsia (p < 0.025); the prevalence of HSV2 antibody was significantly higher in patients with duodenal or gastric ulcer, than in those with non-ulcer dyspepsia (p < 0.05, p < 0.01, respectively); however, antibody levels (mean optical density) to the viruses studied were similar for all groups of patients. These results provide some evidence that HSV might be implicated in the pathogenesis of peptic ulcer disease.     

Helicobacter pylori density and cagA status in cirrhotic patients: a case-control study

BACKGROUND AND AIM: Despite a similar Helicobacter pylori prevalence, peptic ulcer is more frequent in cirrhotic patients than in controls. We evaluated whether cirrhotic patients had an increased bacterial density and/or a higher prevalence of H. pylori cagA-positive strains than controls. METHODS: A total of 36 dyspeptic cirrhotic patients with H. pylori infection and 72 matched controls were enrolled. H. pylori infection was detected at histology on Giemsa staining, bacterial density was assessed using difference over baseline (DOB) values at 13C urea breath test, and cagA status was established at serology. RESULTS: Overall, both DOB values and prevalence of cagA did not significantly differ between cirrhotic patients and controls. However, peptic ulcer controls showed significantly higher DOB value (27.9 +/- 17.4 vs 19.4 +/- 9.3, respectively; P = 0.009) and cagA positive rate (85%vs 48%; P = 0.01) than non-ulcer dyspepsia patients. Although not statistically significant, a similar trend was observed in cirrhotic patients with peptic ulcer for DOB values (26.5 +/- 16.3 vs 18.3/1000 +/- 9.2, respectively; P = 0.07), whereas the cagA-positive rate was similar between peptic ulcer and non-ulcer dyspepsia patients (60%vs 50%; P = 0.30). CONCLUSIONS: The present data showed that both bacterial density and cagA prevalence did not differ between cirrhotic patients and controls.     

Serologic detection of CagA positive Helicobacter pylori strains predicts the presence of peptic ulcer in young dyspeptic patients.

BACKGROUND: Helicobacter Pylori infection has been strongly associated with upper gastrointestinal (GI) disease, especially duodenal ulcer. Endoscopy or contrast radiography is needed to diagnose and appropriately manage peptic ulcer disease. These diagnostic procedures, however, are time consuming and expensive; endoscopy is invasive and contrast radiography cannot help in the diagnosis of H pylori infection. Our aim was to examine in a prospective study the relation between serologic detection of cytotoxic associated gene (CagA) H pylori strains and endoscopic findings among young dyspeptic patients to determine whether this noninvasive test can help differentiate patients with from those without ulcers. METHODS: One hundred patients younger than 45 years with dyspepsia referred for upper GI endoscopy were included in the study. During endoscopy antral biopsy specimens were obtained for the rapid urease test and histologic examination. At histologic examination gastritis was graded from 0 (normal histologic features) to 3 (severe gastritis). After endoscopy blood was obtained for serologic determination of CagA status. RESULTS: Among the 100 patients 56 were H pylori positive and 44 were H pylori negative. In the group of 56 H pylori-positive patients 36 (64.3%) had peptic ulcers and 20 (35.7%) did not. Among patients with peptic ulcer 34 of 36 (94.4%) were CagA positive and 2 (5.6%) were CagA negative. The respective values for the group of patients without ulcers were 9 of 20 (45%) and 11 of 20 (55%). The difference in the proportion of CagA-positive subjects between the group with and that without peptic ulcer was highly significant (p < 0.0001). CONCLUSIONS: Among young patients with dyspepsia, CagA seropositivity is highly associated with duodenal ulcer at endoscopy.     

Overexpression of co-stimulatory molecules in peripheral mononuclear cells of Helicobacter pylori-positive peptic ulcer patients: possible difference in host responsiveness compared with non-ulcer patients

BACKGROUND/AIM: Helicobacter pylori is the principal cause of gastritis and peptic ulcer disease. However, H. pylori-positive patients do not always have peptic ulcer. This study was carried out in order to determine the difference in host immune reaction to H. pylori between patients with peptic ulcer and those without. METHODS: Ten H. pylori-positive patients with peptic ulcer, 10 H. pylori-positive non-ulcer patients, and 10 healthy volunteers were examined for expression of surface molecules in peripheral blood mononuclear cells. The surface molecules were stained with immunofluorescence-labelled specific antibodies and analysed by flow cytometry. RESULTS: More mononuclear cells expressed molecules ICAM-1, VLA-4, Leu-M3 in H. pylori-positive ulcer patients than in non-ulcer patients and healthy volunteers. There were also more cells expressing CD28, SLe(x), CD4, HLA-DR, and NU-B2 in H. pylori-positive ulcer patients than in non-ulcer patients and healthy volunteers. There were fewer cells expressing CD8 in H. pylori-positive ulcer patients than in non-ulcer patients and healthy volunteers. CONCLUSION: H. pylori infection may cause immunological reactions which are reflected in peripheral mononuclear cells. However, the activity and characteristics of peripheral mononuclear cells, in terms of expression of adhesion molecules, may differ between ulcer and non-ulcer patients who are infected with H. pylori.     

Importance of Helicobacter pylori cagA and vacA status for the efficacy of antibiotic treatment

BACKGROUND: Virulence factors of Helicobacter pylori are associated with peptic ulcer disease and may be also associated with the efficacy of treatment. AIMS: To determine the relation between the vacA and the cagA status of H pylori, clinical disease, and treatment outcome. PATIENTS: 121 patients with H pylori infection and peptic ulcer disease or functional dyspepsia were treated by quadruple antibiotic therapy in two groups for one and two days, respectively. METHODS: DNA was isolated from gastric antral biopsy specimens, taken before and after treatment, and the vacA and cagA status was determined by polymerase chain reaction and reverse hybridisation. RESULTS: Peptic ulcer disease was significantly associated with the vacA s1 type, and cagA positivity, but not with the vacA m type. Treatment efficacy was significantly higher in patients with peptic ulcer disease, or infected with cagA+/vacA s1 strains. CONCLUSIONS: The strong association between the cagA and vacA status and peptic ulcer disease was confirmed. Cure rates seem to be higher for patients with cagA+/vacA s1 H pylori strains, which is consistent with the higher cure rate observed among ulcer patients compared with functional dyspepsia patients. Therefore, treatment studies may require stratification for presence of ulcers as well as H pylori genotypes.     

Association of peptic ulcer with increased expression of Lewis antigens but not cagA, iceA, and vacA in Helicobacter pylori isolates in an Asian population

BACKGROUND: Studies in Western populations suggest that cagA, iceA, and vacA gene status in Helicobacter pylori isolates is associated with increased virulence and peptic ulcer disease. AIM: To investigate the relationship between peptic ulcer and expression of Lewis (Le) antigens as well as cagA, iceA, and vacA in H pylori isolates in Singapore. METHODS: Expression of Le antigens in H pylori isolates obtained from patients with dyspepsia was measured by enzyme linked immunosorbent assay. The cagA, iceA, and vacA status was determined by polymerase chain reaction. RESULTS: Of 108 H pylori isolates, 103 (95.4%) expressed Le(x) and/or Le(y), while Le(a) and Le(b) were expressed in 23 (21.3%) and 47 (43.5%) isolates, respectively. Expression of two or more Le antigens (Le(x), Le(y), Le(a), or Le(b)) was significantly higher in H pylori isolated from ulcer patients than in non-ulcer patients (89.6% v 73.2%, p=0.035). There were no significant differences in the prevalence of cagA or iceA1 in H pylori isolates from peptic ulcer and non-ulcer patients (86.6% v 90.2% for cagA; 70.1% v 68.3% for iceA1), and no association of peptic ulcer with any specific vacA genotype. CONCLUSIONS: The present study indicates that peptic ulcer disease is associated with increased expression of Lewis antigens but not cagA, iceA, or vacA genotype in H pylori isolates in our population. This suggests that cagA, iceA, and vacA are not universal virulence markers, and that host-pathogen interactions are important in determining clinical outcome.     

Helicobacter pylori and gastritis in patients with peptic ulcer and non-ulcer dyspepsia: ethnic differences in Singapore.

Peptic ulcer occurs with different frequencies in the three main racial groups in Singapore. This study aimed firstly to determine the prevalence of Helicobacter pylori in peptic ulcer and non-ulcer dyspepsia patients of the different races and secondly, to assess the relation between H pylori, histological gastritis, patient diagnosis, and race. Gastric antral biopsy specimens from 1502 patients undergoing gastroduodenoscopy were studied and 892 (59%) were positive for H pylori. H pylori was strongly associated with gastritis: 873 of 1197 (73%) patients with gastritis were positive compared with 19 of 305 (6%) without gastritis (p less than 0.0001). The prevalences of H pylori and gastritis were similar in peptic ulcer patients of different races. Malay patients with non-ulcer dyspepsia, however, were less likely to be positive for H pylori (10 of 46 (22%] or to have antral gastritis (17 of 46 (37%] than Chinese (292 of 605 (48%) were positive for H pylori and 421 of 605 (70%) had gastritis) and Indians (35 of 61 (57%) were H pylori positive and 42 of 61 (69%) had gastritis). Patients with duodenal ulcer were more likely to be positive for H pylori than those with non-ulcer dyspepsia, even when subjects with gastritis were considered separately. While our results do not help to explain the observed racial differences in peptic ulcer frequency it may be that the pathophysiology of non-ulcer dyspepsia is different in the different races in Singapore.     

Helicobacter pylori infection in patients with ulcer recurrence after partial gastrectomy

BACKGROUND/AIMS: Recurrent ulceration of the stomach occurs in some patients after surgery for peptic ulcer disease. The aim of this study is to evaluate the association of Helicobacter pylori infection with ulcer recurrence in patients after partial gastrectomy due to peptic ulcer disease. METHODOLOGY: A total of 186 patients after partial gastrectomy with Billroth I or Billroth II anastomosis presenting with dyspepsia or bleeding were included. An ulcer recurrence was documented by endoscopic examination. Biopsy specimens were taken from the remnant gastric bodies in all patients. H. pylori infection was diagnosed by either a positive biopsy urease test or the presence of the microorganism on histology. RESULTS: Eighty-three (44.6%) patients among the 186 patients had recurrent ulcers. H. pylori infection was found in 29 (36%) patients in the ulcer group and 42 (41%) patients in the non-ulcer group. The incidence of H. pylori infection did not differ significantly between the two groups (P>0.05). CONCLUSIONS: H. pylori infection may not play an important role in the pathogenesis of recurrent ulcer after partial gastrectomy. Other factors should be studied further.     

vacA genotypes of Helicobacter pylori in relation to cagA status and clinical outcomes in Iranian populations

Mosaicism in vacA alleles with two distinct families of vacA signal sequences (s1 and s2) and two distinct families of middle region alleles (m1 and m2) has been reported. Research suggests that the vacA s1 genotype is closely associated with duodenal ulcer disease and with high cytotoxin production. The aims of this study were to evaluate the role of vacA genotyping with respect to gastric inflammation and injury, and clinical presentation in Iranian populations. Genomic DNA of biopsy specimens from patients with gastritis, peptic ulcer disease (PUD), or gastric cancer (GC) were characterized based on ureC (glmM), cagA, and vacA genotyping by using polymerase chain reaction. Of 167 patients including 33 with PUDs, 129 with non-ulcer dyspepsia (NUD), and 5 with GC, 96 (57.5%) cases were infected by Helicobacter pylori. Among these patients, H. pylori were isolated from 19 (57.7%) PUD patients, 74 (68.7%) NUD patients, and 3 (60%) GC patients. The cagA was detected in 76% of H. pylori-positive cases. The vacA s1-m2 genotype was the most prevalent in 7/19 PUD (37%) and 30/74 NUD (40.5%) patients with H. pylori infection. The prevalence of vacA s2-m1 (8%) was high in Iranian isolates. A significant association was not found between H. pylori genotypes and clinical outcomes. The vacA genotypes and cagA status were not useful markers for gastroduodenal diseases in Tehran, Iran.     

Direct determination of Helicobacter pylori vacA genotypes and cagA gene in gastric biopsies and relationship to gastrointestinal diseases

OBJECTIVE: Our aim was to detect Helicobacter pylori (H. pylori) from gastric biopsies of 248 patients using a novel, polymerase chain reaction (PCR)-based methodology, which simultaneously facilitates the determination of H. pylori vacA genotypes and cagA gene. METHODS: A simple methodology for sample preparation was established and PCR was performed with primer systems for the 16S rRNA, vacA, and cagA genes, thus circumventing the need to culture H. pylori and to extract DNA from biopsy samples. RESULTS: Infection with H. pylori was detected in 147 (59.3%) of 248 patients. The vacA signal sequence genotype s1 was present in 104 (81.3%) of 128 H. pylori-positive patients, and 24 (18.8%) patients had the genotype s2. The vacA middle region types m1 and m2 were detected in 46 (35.9%) and 79 (61.7%) patients, respectively. The combinations s1/m2 (43%) and s1/m1 (35.9%) were found more frequently than s2/m2 (18.8%). The cagA gene was detected in 75 (72.1%) of 104 H. pylori-positive biopsies with the vacA genotype s1. All 24 biopsies with the type s2 were cagA negative. Strains of the type vacA s1 were found in 97% of H. pylori-positive patients with peptic ulcer disease and were associated with the presence of the cagA gene, whereas 96% of the strains of the type vacA s2 were detected in patients who only had nonulcer dyspepsia. CONCLUSIONS: Using a novel PCR-based methodology, H. pylori 16S rRNA gene, vacA genotypes, and cagA gene can now be rapidly detected directly in gastric biopsies with high accuracy. These data demonstrate that infection with H. pylori strains of the vacA s1 genotype and the cagA gene are more likely to result in peptic ulcer disease. Determination of vacA genotypes and cagA gene may contribute to the potential clinical identification of patients at different levels of risk.     

Anti-CagA and anti-VacA antibodies in Helicobacter pylori-infected patients with and without peptic ulcer disease in Serbia and Montenegro

BACKGROUND: The expression of two Helicobacter pylori proteins, CagA and VacA, is associated with more severe pathogenesis and clinical outcomes of the infection. However, this association varies among geographical regions and ethnic groups. We therefore evaluated CagA and VacA seroprevalence in H. pylori-positive dyspeptic patients in Serbia and Montenegro. METHODS: In 173 consecutive dyspeptic patients referred to endoscopy (67M, mean age 49 +/- 15, 76 smokers), immunoblot assay was used to detect serum antibodies against CagA and VacA. Presence of H. pylori infection was assessed using a rapid urease test (RUT), routine histology and serology (anti-IgG ELISA). Duodenal ulcer (DU) was diagnosed in 28, gastric ulcer (GU) in 3 and non-ulcer dyspepsia (NUD) in the remaining 142 patients. RESULTS: 129 (74.6%) patients were H. pylori-positive, 27 (96.4%) with DU, 3 (100%) with GU and 99 (69.7%) with NUD (P < 0.01); 121 (93.8%) patients carried anti-CagA antibodies and there was no difference between the DU and NUD groups. VacA antibodies were detected in sera of 50 (38.75%) and were more prevalent in patients with DU compared to the NUD group (P < 0.05). CONCLUSIONS: In Serbia and Montenegro there is high seroprevalence of CagA-positive H. pylori strains in dyspeptic patients with and without peptic ulcer, while VacA-positive strains are more closely related to peptic ulcer disease.     

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 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.     

Seroprevalence of eight Helicobacter pylori antigens among 182 patients with peptic ulcer, MALT gastric lymphoma or non-ulcer dyspepsia. Higher rate of seroreactivity against CagA and 35-kDa antigens in patients with peptic ulcer originating from Europe and Africa.

BACKGROUND: It has been suggested that Helicobacter pylori may induce more or less severe gastroduodenal disease according to the strain virulence. DESIGN: We used Western blot to determine antigenic profiles associated with duodenal or gastric ulcer disease, MALT lymphoma and non-ulcer dyspepsia, and to identify geographical differences. METHODS: One hundred and eighty-two consecutive patients with H. pylori infection were studied. H. pylori infection was diagnosed by a rapid urease test or histological examination of gastric biopsy samples. Bacterial density and gastritis were assessed histologically by using the Sydney scoring system. Western blot was used to identify antibodies against eight antigens (CagA, VacA, urease A, heat shock protein B, and 19.5, 26.5, 30 and 35 kDa). Patients were questioned on their smoking habits and place of birth and childhood. RESULTS: There were 73 patients with duodenal ulcer, 30 with gastric ulcer, eight with erosive duodenitis, 17 with gastric MALT lymphoma and 54 with non-ulcer dyspepsia. Most (>85%) were seropositive for the heat shock protein B and 26.5-kDa antigens. The prevalence of the other antigens ranged from 45% (VacA) to 68% (urease B). The seroprevalence of CagA antigen was significantly higher (P < 0.01) in cases of gastroduodenal ulcer (84%) than non-ulcer dyspepsia (37%). Similarly, 35-kDa antigen reactivity was more frequent (P < 0.05) in duodenal ulcer patients (75%) than in those with non-ulcer dyspepsia (50%). The antigenic profiles associated with MALT gastric lymphoma and non-ulcer dyspepsia were similar. Multivariate analysis showed that only gastroduodenal ulcer was significantly associated with CagA. Gastroduodenal ulcer and a childhood spent in Africa were both associated with 35-kDa and combined CagA-35-kDa reactivity. CONCLUSIONS: This study confirms the strong seroprevalence of H. pylori CagA antigen and shows a high prevalence of the 35-kDa antigen in patients with gastroduodenal ulcer, especially those raised in Africa. There was no difference in the serological pattern between patients with non-ulcer dyspepsia and those with MALT lymphoma. Tests for antibodies to the CagA-35-kDa antigen combination might be used to select H. pylori-infected dyspeptic patients warranting treatment.     

Are twelve days of omeprazole, amoxicillin and clarithromycin better than six days for treating H. pylori infection in peptic ulcer and in non-ulcer dyspepsia?

BACKGROUND/AIMS: To evaluate whether omeprazole, amoxicillin and clarithromycin for 12 days is more effective for Helicobacter pylori eradication than the same regimen for only 6 days; and to verify whether these eradication regimens are more effective in peptic ulcer disease than in non-ulcer dyspepsia. METHODOLOGY: We studied 411 patients in whom a gastroscopy was carried out due to symptoms related to the upper gastrointestinal tract and who were diagnosed with duodenal ulcer (175 patients, 43%), gastric ulcer (42 patients, 10%), or non-ulcer dyspepsia (194 patients, 47%), and concomitant infection by H. pylori. At endoscopy, biopsies were obtained for rapid urease test, and a 13C-urea breath test was carried out. Urea breath test was repeated four weeks after completing eradication treatment with 1) omeprazole (20 mg b.i.d.), amoxicillin (1 g b.i.d.) and clarithromycin (500 mg b.i.d.) for six days (239 patients), or 2) the same regimen for 12 days (172 patients). RESULTS: H. pylori eradication was achieved in 73.6% (95% CI, 68-79%) of the patients treated during 6 days, and in 84.3% (79-90%) of those receiving 12 days of therapy (P < 0.01). The overall eradication rate with both regimens (6 plus 12 days), respectively in patients with duodenal ulcer, gastric ulcer and non-ulcer dyspepsia, was 84.6% (79-90%), 75.6% (61-86%), and 72.8% (67-79%) (P < 0.01 when comparing duodenal ulcer vs. non-ulcer dyspepsia). Twelve-day regimen was more effective than 6-day regimen only in non-ulcer dyspepsia (62% vs. 83%, P < 0.01), but not in duodenal or gastric ulcer. In the multivariate analysis the duration (6 vs. 12 days) of eradication therapy (odds ratio: 2.2; 1.3-3.7) and the type of disease (duodenal ulcer vs. non-ulcer dyspepsia; odds ratio: 2.3; 1.3-3.8) were the only variables which influenced on H. pylori eradication efficacy (chi 2 model, 17; P < 0.001). CONCLUSIONS: Efficacy with omeprazole-amoxicillin-clarithromycin regimen in patients with duodenal ulcer is higher than in those patients with non-ulcer dyspepsia. The increase of H. pylori eradication rate by 21% in our non-ulcer dyspepsia patients justifies the prolongation from 6 to 12 days of omeprazole-amoxicillin-clarithromycin therapy, whilst the increase of cure rates in duodenal or gastric ulcer patients with a 12-day therapy would not be cost-effective.     

H pylori infection among 1000 southern Iranian dyspeptic patients

INTRODUCTION H pylori is a major cause of gastritis and peptic ulcer disease (PUD), and has been implicated in the development of gastric malignancy[1-3]. The prevalence of H pylori, a worldwide infection, varies greatly among countries and among populati…     

Association of CagA and VacA presence with ulcer and non-ulcer dyspepsia in a Turkish population

AIM: The mostly known genotypic virulence features of H. pylori are cytotoxin associated gene A (cagA) and Vacuoliting cytotoxin gene A (VacA). We investigated the association of these major virulence factors with ulcer and non-ulcer dyspepsia in our region. METHODS: One hundred and forty two dyspeptic patients were studied (average age 44.8+/-15.9 years, range 15-87 years, 64 males and 78 females). Antral and corpus biopsies were taken for detecting and genotyping of H. pylori. 107 patients who were H. pylori positive by histological assessment were divided into three groups according to endoscopic findings: Duodenal ulcer (DU), gastric ulcer (GU) and non-ulcer dyspepsia (NUD). The polymerase chain reaction (PCR) was used to detect CagA and VacA genes of H. pylori using specific primers. RESULTS: H. pylori was isolated from 75.4 % (107/142) of the patients. Of the 107 patients, 66 (61.7 %) were cagA-positive and 82 (76.6 %) were VacA-positive. CagA gene was positively associated with DU and GU (P<0.01, P<0.02), but not with NUD (P>0.05). Although VacA positivity in ulcer patients was higher than that in NUD group, the difference was not statistically significant (P>0.05). CONCLUSION: There is a significantly positive association between CagA genes and DU and GU. The presence of VacA is not a predictive marker for DU, GU, and NUD in our patients.     

Risk factors for ulcer development in patients with non-ulcer dyspepsia: a prospective two year follow up study of 209 patients

BACKGROUND AND AIMS: A subset of non-ulcer dyspepsia (NUD) disorders can evolve into peptic ulcer disease. This prospective study attempted to determine the independent risk factors for ulcer formation in NUD patients, and compared the natural history of Helicobacter pylori positive and negative NUD subjects. METHODS: From May 1997 to April 1999, consecutive NUD patients were enrolled into the study. Endoscopy was performed routinely on enrolment, at the end of the second and 12th months, and whenever there was a dyspepsia attack. Patients were prospectively followed up for two years. RESULTS: Peptic ulcers occurred in 16 of 209 NUD patients during the two year follow up period. Multivariate analysis of 13 host and bacterial factors demonstrated that advanced age (odds ratio 2.90), H pylori infection (odds ratio 3.59), and use of non-steroidal anti-inflammatory drugs (NSAID; odds ratio 4.46) were independently significant in predicting subsequent peptic ulcer development. NUD patients with all three risk factors had a 75% (3/4) risk of developing peptic ulcer but the ulcer incidence in patients without any of the risk parameters was only 1.2% (1/84). The resolution rate of symptoms in the H pylori positive NUD patients was similar to the H pylori negative patients (57.9% v 49.1%; 95% confidence interval (CI) -5 to 22). However, rates for subsequent peptic ulcer and erosion development were significantly higher in H pylori positive patients than in H pylori negative patients (ulcer 12.6% v 3.5%, 95% CI 1-16; erosion 23.2% v 12.3%, 95% CI 1-21). CONCLUSION: A small but significant proportion of NUD patients develop peptic ulcer after long term follow up. H pylori infection, NSAID use, and advanced age are independent risk factors for subsequent ulcer formation. Follow up endoscopy is strongly indicated for an NUD patient with multiple risk factors for ulcer formation when symptoms recur.     

The Helicobacter pylori breath test: a surrogate marker for peptic ulcer disease in dyspeptic patients.

BACKGROUND: There is interest in noninvasive H pylori testing as a means of predicting diagnosis and determining management in dyspeptic patients. AIMS: To assess the value of the 14C urea breath test as a predictor of peptic ulcer disease in patients presenting with dyspepsia. PATIENTS AND METHODS: 327 consecutive patients referred for investigation of dyspepsia had a 14C urea breath test performed before endoscopy. Patients were not included if they had previously confirmed ulcer disease, previous gastric surgery, or were taking non-steroidal anti-inflammatory drugs. RESULTS: Of the 182 patients with a positive 14C urea breath test, duodenal and/or gastric ulcers were present in 45% and erosive duodenitis in a further 2%. Oesophagitis was present in 12% of the breath test positive patients with two thirds of the oesophagitis patients having co-existent ulcer disease. The prevalence of ulcer disease in the H pylori positive dyspeptic patients was independently related to smoking and previous investigation status. If previously uninvestigated, the prevalence of ulcers was 67% in smokers and 46% in non-smokers. If previous upper gastrointestinal investigations were negative, the prevalence of ulcers was 53% in smokers and 28% in non-smokers. Of the 136 patients with a negative breath test, only 5% had peptic ulcers. The most frequent endoscopic finding in these H pylori negative subjects was oesophagitis, being present in 17%. CONCLUSIONS: This study demonstrates that a positive H pylori test is a powerful predictor of the presence of underlying ulcer disease in dyspeptic patients, especially if smokers, and that a negative H pylori test is a powerful predictor of the absence of ulcer disease. It also indicates that a negative upper gastrointestinal investigation does not preclude subsequent presentation with ulcer disease.     

Low prevalence of Helicobacter pylori but high prevalence of cytomegalovirus-associated peptic ulcer disease in AIDS patients: Comparative study of symptomatic subjects evaluated by endoscopy and CD4 counts

BACKGROUND AND AIMS: The role of Helicobacter pylori infection in gastroduodenal lesions might be different between the general population and AIDS patients. The aim of the present study was to compare the prevalence of H. pylori and cytomegalovirus (CMV) infection in AIDS patients and HIV-negative controls. The impact of CD4 lymphocyte counts on H. pylori and CMV infection in the same subjects was also assessed. METHODS: One hundred and fifty-six patients (52 HIV-positive, 104 HIV-negative) with gastrointestinal symptoms were evaluated with upper gastrointestinal endoscopy and biopsy. Comparison of the prevalence of H. pylori and CMV infection was made by dividing AIDS patients into two groups: those with CD4 counts >100/mm3 and those with CD4 counts <100/mm3, and ulcer and non-ulcer patients. RESULTS: In comparison with HIV-negative controls, AIDS patients had a lower prevalence of H. pylori infection (P < 0.0001) but a higher prevalence of CMV infection (P < 0.0001). Cytomegalovirus infection was frequently found in AIDS patients with CD4 count <100/mm3, in comparison with those with a CD4 count >100/mm3. In AIDS patients, CMV was more frequently detected in subjects with peptic ulcers (P = 0.0125). Conversely, the prevalence of H. pylori infection in AIDS patients was not different between those with and without peptic ulcers. CONCLUSIONS: The low prevalence of H. pylori infection and peptic ulcer in AIDS patients suggests a different role of H. pylori infection in peptic ulcer or even a different mechanism of peptic ulcerogenesis in HIV-positive subjects. Cytomegalovirus, rather than H. pylori, may be the main causative pathogen of peptic ulcers in AIDS patients.