Cure of Helicobacter pylori-associated ulcer disease through eradication.

The eradication of Helicobacter pylori (H. pylori) infection has led to a dramatic benefit for patients with gastroduodenal ulcer disease, as the majority of these patients receive a lifelong cure. Relapses after successful H. pylori cure may be caused by either recrudescence or reinfection, both rare events nowadays, or be attributed to non-steroidal anti-inflammatory drugs or aspirin intake. In certain geographical areas, H. pylori-negative relapses are proposed as a new, pathophysiological and not yet elucidated entity. The cure of H. pylori infection in uncomplicated duodenal ulcer diseases consists of 7 days of proton pump inhibitor (PPI) based triple therapy, containing two antibiotics from clarithromycin, amoxicillin and metronidazole. In gastric ulcer, it is recommended that the PPI is continued for a further 3 weeks as these ulcers have a prolonged healing time. Rescue therapies after failure need to take into consideration the resistance pattern of the micro-organism and are offered in the form of quadruple therapy or a high-dose PPI with amoxicillin.     

Helicobacter pylori-associated antibodies in patients with duodenal ulcer, gastric and oesophageal adenocarcinoma

OBJECTIVE: To associate Helicobacter pylori-associated antibodies with clinical disease in groups of patients with duodenal ulcer, gastric adenocarcinoma, oesophageal adenocarcinoma and normal mucosa. DESIGN: Prospective observational sero-epidemiology study. Identification of consecutive in-patients with duodenal ulcer, gastric adenocarcinoma, oesophageal adenocarcinoma and normal mucosa. Analyses of sera for antibodies to whole H. pylori, Cag A and Vac A antigens using ELISA and Western blot. Statistical analyses. SETTING: Walsgrave Hospital, Coventry, a district general hospital that serves a population of 350,000. PARTICIPANTS: Consecutive in-patients with an endoscopic diagnosis of duodenal ulcer (n = 31), gastric adenocarcinoma (n = 31), oesophageal adenocarcinoma (n = 40) and normal mucosa (n = 46). MAIN OUTCOME MEASURES: A profile of antibodies was constructed for each patient group and between-group comparisons were made. A logistic regression model determined the H. pylori-associated antibody that could best predict a patient's diagnosis. A discriminatory power for each antibody was calculated. RESULTS: Whole H. pylori, Cag A and Vac A antibodies are found more commonly in duodenal ulcer patients when compared to oesophageal adenocarcinoma (P < 0.003) and normal mucosa patients (P < 0.015). Similarly, gastric adenocarcinoma patients have antibodies to whole H. pylori, Cag A and Vac A more frequently than oesophageal adenocarcinoma (P< 0.002) and normal mucosa patients (P < 0.006). Vac A antibodies discriminate between duodenal ulcer/gastric adenocarcinoma and oesophageal adenocarcinoma/normal mucosa patients (odds ratio 5.56, log likelihood -90.06, P < 0.001) more effectively than Cag A antibodies (odds ratio 4.17, log likelihood -91.88, P < 0.001). CONCLUSIONS: Similar profiles of H. pylori-associated antibodies are seen in patients with duodenal ulcer and gastric adenocarcinoma, confirming that virulent H. pylori are involved in the pathogenesis of both diseases. Antibodies to Vac A could be used to identify patients at increased risk of developing H. pylori-associated disease.     

Helicobacter pylori infection density and gastric inflammation in duodenal ulcer and non-ulcer subjects.

The factors that determine which Helicobacter pylori infected subjects develop duodenal ulcer (DU) are unclear. This study tested the hypothesis that infection density and urease activity are higher in DU than non-DU subjects. Fifty five DU and 55 age and sex matched non-DU subjects were studied. Quantitative methods were used for measuring infection density (viable organism count) and urease activity (Berthelot reaction). DU subjects had a greater antral infection density (geometric mean of colony forming units/mg biopsy protein; 10.5 x 10(5) v 1.3 x 10(5), p < 0.001). They also had higher biopsy urease activity (geometric mean of NH3 nmol/min-1/mg protein-1; 103 v 25, p < 0.001). Urease activity per organism, however, was similar in the two groups showing that high antral urease activity in DU was a reflection of organism density. DU was not present in subjects with an antral infection density less than 10(5) colony forming units/mg protein. A correlation was present between H pylori viable counts and the severity and activity of gastritis. Both severity and activity of gastritis were greater in the antrum of DU compared with non-DU subjects but there was no difference in the body between the two groups. It is concluded that antral H pylori infection density is probably an important determinant of DU development, and that there is a baseline of infection density that is necessary for ulcer formation.     

The course of Helicobacter pylori-associated duodenal ulcer concurrent with chronic opisthorchiasis

The purpose of the investigation was to study the specific features and the course of Helicobacter pylori-associated duodenal ulcer (DU) concurrent with chronic opisthorchiasis (CO) A hundred and twenty-seven patients with H. pylori-associated DU were examined. Of them 78 patients were found to have H. pylori-associated DU concurrent with CO. In mixed pathology, asthenovegetative disorders were observed in most patients, one third had eosinophilia. With an over 10-year history of CO, acid production and pepsin secretion substantially decreased in both phases of gastric secretion. Mucosal atrophic changes were found mainly in the antral portion of the stomach, which frequency correlated with the duration of Opisthorchis invasion. The incidence of atrophic duodenitis tripled. All the patients received eradication therapy by the classical first-line treatment regimen including omeprazole and the antibiotics clarithromycin and amoxicillin. In the mixed pathology group, the time of ulcerative defect scarring increased by an average of 5 days. Fifty-eight with pathology continuously receiving the antisecretoty agent underwent dehelminthization with the anthelminthic bilthricide in 33 patients and with the plant anthelminthic dry aspen bark extract in 25. Evaluation of the efficiency of eradication therapy indicated that the best results of H. pylori eradication had been achieved in the patients dehelminthized with bilthricide. Assessment of long-term results showed that after multimodality therapy (eradication followed by bilthricide dehelminthization), there were no relapses for 2 years and there was a drop in the number of patients resorting to on-request therapy in patients with H. pylori-associated DU concurrent with CO.     

A four-year follow-up of duodenal ulcer patients after Helicobacter pylori eradication.

BACKGROUND/AIMS: The aim of our study was to evaluate the clinical course of disease in 63 duodenal ulcer (DU) patients during a 4-year follow-up after Helicobacter pylori (H. pylori) eradication. METHODOLOGY: Upper gastrointestinal endoscopy and a clinical interview were performed before antimicrobial therapy, 2 months after, yearly and when symptoms recurred. Two antral and two corporal specimens were taken for histology, and one additional specimen from antrum was taken for rapid urease test at the first endoscopy and for culture at the following endoscopies. All patients received triple antimicrobial regimens based on colloidal bismuth subcitrate, amoxycillin and metronidazole for at least 2 weeks. Patients with a negative histology and culture 2 months after antimicrobial therapy were included in the study. RESULTS: After H. pylori eradication, ulcer recurrence dropped from 84.1% per year in the year before H. pylori eradication to a mean value of 5.2% per year during 2076 patient months (p<0.01). The increased incidence of gastroesophageal reflux disease (GERD) was found only in the first year of the follow-up period. The average percentage of anti-ulcer drug users per year was 30.8% because of GERD, reflux symptoms, ulcer recurrence or non-ulcer dyspepsia. Ulcers or acute erosions recurred in 9 H. pylori-negative patients; recurrences were attributable to non-steroidal anti-inflammatory drugs (NSAID) in 4 out of 9 cases (44.4%). CONCLUSIONS: H. pylori eradication changed the long-term course of DU disease.     

History of Helicobacter pylori,duodenal ulcer,gastric ulcer and gastric cancer

Helicobacter pylori(H.pylori)infection underlies gastric ulcer disease,gastric cancer and duodenal ulcer disease.The disease expression reflects the pattern and extent of gastritis/gastric atrophy(i.e.,duodenal ulcer with non-atrophic and gastric ulcer and gastric cancer with atrophic gastritis).Gastric and duodenal ulcers and gastric cancer have been known for thousands of years.Ulcers are generally non-fatal and until the 20th century were difficult to diagnose.However,the presence and pattern of gastritis in past civilizations can be deduced based on the diseases present.It has been suggested that gastric ulcer and duodenal ulcer both arose or became more frequent in Europe in the 19th century.Here,we show that gastric cancer and gastric ulcer were present throughout the 17th to 19th centuries consistent with atrophic gastritis being the predominant pattern,as it proved to be when it could be examined directly in the late 19th century.The environment before the 20th century favored acquisition of H.pylori infection and atrophic gastritis(e.g.,poor sanitation and standards of living,seasonal diets poor in fresh fruits and vegetables,especially in winter,vitamin deficiencies,and frequent febrile infections in childhood).The latter part of the 19th century saw improvements in standards of living,sanitation,and diets with a corresponding decrease in rate of development of atrophic gastritis allowing duodenal ulcers to become more prominent.In the early 20th century physician’s believed they could diagnose ulcers clinically and that the diagnosis required hospitalization for"surgical disease"or for"Sippy"diets.We show that while H.pylori remained common and virulent in Europe and the United States,environmental changes resulted in changes of the pattern of gastritis producing a change in the manifestations of H.pylori infections and subsequently to a rapid decline in transmission and a rapid decline in all H.pylori-related diseases.     

Helicobacter pylori-associated gastric ulcer exhibits enhanced mucosal chemokine activity at the ulcer site

BACKGROUND AND AIM: Although mucosal alpha- and beta-chemokines are considered to be involved in the pathogenesis of Helicobacter pylori-associated gastritis, little is known how these chemokines are related to the ulcerogenesis in peptic ulcer patients. We examined the levels of interleukin (IL)-8 and macrophage inflammatory protein-1alpha (MIP-1alpha) in organ cultures and the numbers of inflammatory cells infiltrating the lamina propria by using the mucosal tissues obtained from gastric ulcer (GU) patients with and without H. pylori infection. METHODS: Levels of IL-8 and MIP-1alpha secreted in organ cultures were measured by an enzyme-linked immunosorbent assay. Numbers of myeloperoxidase-positive neutrophils, CD68-positive macrophages, and mononuclear cells were determined in tissue sections. RESULTS: The mucosal tissues of both the gastric antrum and the ulcer site obtained from patients with H. pylori-positive GU showed significantly higher levels of IL-8 and MIP-1alpha and increased numbers of inflammatory cells compared with the corresponding mucosal tissues from those with H. pylori-negative GU or the antral mucosal tissues from H. pylori-negative controls. When the values were compared between the mucosal tissues from the gastric antrum and those from the ulcer site, the latter group of tissues showed significantly higher levels of IL-8 and MIP-1alpha and increased numbers of neutrophils and macrophages than the former group regardless of its healing process in patients with H. pylori-positive GU. CONCLUSION: Mucosal alpha- and beta-chemokines may be important to the ulcerogenesis in H. pylori-associated GU disease.     

Link betweenHelicobacter pylori-associated gastritis and duodenal ulcer

We examined the interrelationships among the degree of fundic mucosal atrophy, the prevalence ofHelicobacter pylori in the gastric antrum, the gastric juice, and the duodenum with and without gastric metaplasia, in 20 duodenal ulcer patients and 20 non-duodenal ulcer patients. The detection rates ofH. pylori in the antrum, the gastric juice, and the duodenum were significantly higher in duodenal ulcer patients (80%, 65%, and 60%) than in non-duodenal ulcer subjects (50%, 20%, and 5%). The frequency ofH. pylori was significantly lower in the gastric juice (30%) and the duodenum (10%) in non-duodenal ulcer patients with antralH. pylori, compared with those in duodenal ulcer patients with antralH. pylori. All of seven patients with both gastric metaplasia andH. pylori infection in the duodenum had duodenal ulcer, whereas only 1 of 14 patients without either gastric metaplasia orH. pylori infection in the duodenum had duodenal ulcer. There was normal or mild atrophic mucosa in the fundus of duodenal ulcer patients withH. pylori in the antrum, whereas moderate or severe atrophic mucosa in non-duodenal ulcer patients withH. pylori gastritis. These results suggest that the preserved fundic mucosa, gastric metaplasia in the duodenum, and a greater load ofH. pylori to the duodenum through the gastric juice may be prerequisites for the formation of duodenal ulcers.     

Helicobacter pylori eradication improves pre-existing reflux esophagitis in patients with duodenal ulcer disease.

BACKGROUND & AIMS: There has been significant controversy over the relationship between Helicobacter pylori infection and reflux esophagitis. We investigated the effects of eradicating H. pylori on the reflux esophagitis found in patients with peptic ulcers. METHODS: Prospective posteradication evaluations were conducted yearly in 162 H. pylori-positive patients who had reflux esophagitis together with peptic ulcer disease (4 women and 158 men, mean age = 49.1 yr). The Los Angeles classification of the patients' esophagitis was: grade A, 90; grade B, 63; and grade C, 9. The follow-up evaluations began 1 to 2 months after completion of the eradication treatment (mean time of follow-up = 22 mo), and consisted of endoscopy and an interview focusing on heartburn. RESULTS: Six patients were withdrawn from the study because of adverse drug reactions or a failure to regularly keep their appointments. After eradication therapy, we observed endoscopically that reflux esophagitis had improved in 87 (55.8%) of the 156 patients. The improvement rate was significantly higher in patients cured of infection (60.8%) than in those with persistent H. pylori infection (38.9%) (P = 0.04). Body mass index (odds ratio = 0.86, 95% confidence interval [CI] = 0.76-0.97), cure of infection (3.68, 95% CI = 1.56-8.69), the absence of a hiatal hernia (3.90, 95% CI = 1.83-8.28), and an ulcer located in the duodenum (2.75, 95% CI = 1.33-5.70) were identified as significant independent factors for the improvement of reflux esophagitis. CONCLUSIONS: In patients with reflux esophagitis associated with duodenal ulcer, a significant improvement in pre-existing reflux esophagitis was noted after H. pylori eradication.     

Helicobacter pylori-negative duodenal ulcer.

PURPOSE PATIENTS AND METHODS: Helicobacter pylori (HP) is present in more than 90% of duodenal ulcers (DUs). To investigate the pathophysiology in those patients with DU who are HP-negative compared with those who are HP-positive, we interviewed consecutive patients prior to endoscopy regarding factors often associated with ulcer disease. At esophagogastroduodenoscopy, antral biopsy specimens were obtained for urease test, culture, and Warthin Starry staining for HP in all patients with DU who did not have active bleeding. RESULTS: Compared with HP-positive patients who had DU, HP-negative patients with DU were more likely to be aspirin users and less likely to have had prior ulcers. HP-positive patients with DU had more severe antral inflammation than HP-negative patients. Whites were more likely to be HP-negative than blacks. HP-negative patients with DU most commonly presented with bleeding, whereas HP-positive patients with DU presented with pain. CONCLUSIONS: Our findings suggest a different mechanism for DUs in patients who are HP-positive versus those who are HP-negative, and this difference might have a bearing on treatment. The absence of HP should lead to a more thorough search for nonsteroidal anti-inflammatory drug/aspirin use, Zollinger-Ellison syndrome, and other potential causes of DUs.     

Helicobacter pylori-associated gastritis and gastric cancer in Nigeria.

BACKGROUND: The etiology of gastric cancer has not been clearly delineated. There is some evidence of an association of gastric cancer with Helicobacter pylori-induced chronic gastritis, atrophic gastritis and intestinal metaplasia. Previous studies report a high rate of H. pylori infection and chronic gastritis among Nigerians. METHODS: We retrospectively reviewed 84 tissue specimens with gastric cancer seen in our department over an 18-year period for for the presence of H. pylori infection, chronic gastritis, atrophic gastritis, and intestinal metaplasia in the adjacent non-cancerous gastric mucosa. RESULTS: H. pylori infection was detected in 15 (17.9%) of 84 specimens. Moderate to severe gastritis was found in non-cancerous areas in 77 (91.7%) specimens, and was equally frequent in patients with 'intestinal' and 'diffuse' types of cancer. Atrophic gastritis and intestinal metaplasia were observed in 22 (26.2%) and 35 (41.7%) specimens, respectively, and were more common in 'intestinal' type of gastric cancer. CONCLUSION: Chronic gastritis was seen in the adjacent non-cancerous mucosa in most specimens with gastric cancer. However, its severity did not correlate with the histological subtype of gastric cancer.     

The systemic cellular immune response in the Helicobacter pylori-associated duodenal ulcer and chronic antral gastritis

BACKGROUND/AIMS: The exact pathogenesis of Helicobacter pylori infection is not fully understood. This study aims to evaluate the specific subset composition of peripheral blood lymphocytes in patients with H. pylori-positive duodenal ulcer n = 14), chronic antral gastritis n = 28), since reports so far have led to inconclusive and conflicting results. METHODOLOGY: 42 patients with dyspepsia and 50 controls underwent the following procedures: 1) gastroscopy and gastric biopsy (five specimens) 2) histology, 3) serologic test for anti-H. pylori antibodies IgG (Pyloriset EIA-G, Orion Diagnostica) and anticytotoxin associated gene A (cag A) IgG antibodies (VIVA Diagnositika by ELISA), 4) analysis of the peripheral blood lymphocytes using monoclonal antibodies reacting with lymphocyte cell surface antigens (anti-CD3, anti-CD19, anti-CD4, anti-CD8, anti-CD16 + CD56, anti-HLA DR) by flow-cytometry (Becton-Dickinson) to detect possible changes in the lymphocytes subpopulations in patients with duodenal ulcer and chronic antral gastritis. RESULTS: We found no alteration in total T and B lymphocytes and CD4+ T, CD8+ T lymphocytes and natural killer cells of both duodenal ulcer and chronic antral gastritis patients compared to normal persons. Although there was a slight increase in the proportion of active T lymphocytes in duodenal ulcer and chronic antral gastritis groups comparing to healthy subjects the difference was not statistically significant. CONCLUSIONS: These data indicate that there is no systemic alteration in the specific immune system in response to H. pylori in patients with duodenal ulcer and chronic antral gastritis.     

Regression of duodenal gastric metaplasia in Helicobacter pylori positive patients with duodenal ulcer disease.

BACKGROUND: It is unclear whether the extent of duodenal gastric metaplasia is due to Helicobacter pylori and/or acid. AIMS: To investigate the role of Helicobacter pylori eradication in the regression of duodenal gastric metaplasia in patients with duodenal ulcer maintained in acid suppression conditions. METHODS:. Duodenal (anterior, superior inferior walls of first part of duodenum) and gastric antrum biopsies were obtained from 44 Helicobacter pylori positive duodenal ulcer patients. Helicobacter pylori infection was diagnosed by rapid urease test, histology and 13C-Urea Breath Test. Patients were treated with 20 mg omeprazole tid associated with 250 mg clarithromycin and 500 mg amoxycillin four times daily for 10 days and maintained with 20 mg omeprazole daily for 18 weeks. Control endoscopies were performed at 6 and 18 weeks after beginning treatment. RESULTS: Duodenal gastric metaplasia regression was observed in all (32/32) patients in whom Helicobacter pylori was eradicated, but in only 3 out of 6 patients in whom eradication was not achieved (p<0. 001). CONCLUSIONS:. The present results suggest that Helicobacter pylori eradication associated with prolonged acid suppression may represent a good therapeutic strategy to achieve duodenal gastric metaplasia regression and highlight the combined role of acid and Helicobacter pylori in the pathogenesis of duodenal gastric metaplasia.     

Helicobacter pylori eradication dramatically improves inflammation in the gastric cardia

OBJECTIVES: Inflammation of the gastric cardia, i.e., "carditis," has been associated with Helicobacter pylori (H. pylori) infection; however, some investigators believe carditis to be a histological marker for gastroesophageal reflux disease. The aim of this study was to investigate the role of H. pylori eradication on the grade of carditis scored according to the updated Sydney classification. METHODS: Consecutive patients presenting for upper endoscopy underwent systematic gastric biopsies (eight antral, 12 corpus, and four cardia). Patients with H. pylori infection and carditis were identified and followed prospectively before and after H. pylori treatment. At pretreatment and, on average, 2 yr after eradication of H. pylori, the degree of inflammation in the gastric cardia and H. pylori status were blindly assessed by a single pathologist. RESULTS: A total of 31 patients with H. pylori infection and carditis were identified. The mean age was 70 yr (range: 37-81 yr); all were male. Four were African-American and 27 were Caucasian. All patients were treated with standard anti-H. pylori therapy, including a proton pump inhibitor in combination with two antibiotics for 2 wk. Eradication of H. pylori was successful in 23 patients (group I), whereas eight patients had persistent infection (group II). Patients were followed after eradication therapy for a mean of 23.2 months (range: 6-48 months). After eradication therapy, there was a significant decrease (p < 0.0001) in the carditis scores (activity and inflammation scores) in group I, whereas the scores remained unchanged in group II patients. In both groups, there were no significant changes in the degree of intestinal metaplasia or atrophy. There were four patients with intestinal metaplasia, and one with atrophy. CONCLUSIONS: There is a dramatic improvement in the degree of inflammation and activity scores in the gastric cardia of patients with successful H. pylori eradication compared to those with persistent infection. By fulfilling one of Koch's postulates (i.e., improvement in the disease after cure of the possible etiological organism), these data support H. pylori as being the etiological agent for carditis in this group of patients.