Helicobacter Pylori-positive Patients Research Articles

Corpus‐predominant gastritis as a risk factor for false‐negative 13C‐urea breath test results

Urea breath test sensitivity seems affected by increased intragastric acidity during therapy with antisecretory drugs. Intragastric pH is increased in patients with corpus gastritis with/without atrophy. To test the hypothesis that urea breath test results may also be affected by this gastritis phenotype. 123 untreated patients underwent gastroscopy plus biopsies and intragastric pH measurement. The study included 82 endoscopically proven Helicobacter pylori-positive patients who were offered urea breath test with an acidic meal. Histological findings, urea breath test results and intragastric pH were compared in 66 of the subjects. 21 of 66 (31.8%) patients had a false-negative urea breath test. In these patients corpus-predominant gastritis (85.7% vs. 37.7%; P = 0.0004) and fundic atrophy (66.6% vs. 17.7%; P = 0.0001) were more frequent than in patients with true-positive urea breath test. Intragastric pH was higher in false-negative patients (mean 6.3 vs. 4.4; P = 0.001). In a multivariate analysis, the only risk factor for a false-negative urea breath test was the presence of corpus-predominant gastritis (OR = 5.6; 95% CI: 1.1-27). There was a negative correlation between the intragastric pH and the delta over baseline values (r = -0.378; P = 0.0023). Our results support the hypothesis that the pattern of gastritis can affect the sensitivity of urea breath test, and suggest that patients with corpus-predominant gastritis have a high risk of false-negative urea breath test results.

Erythrocyte Lewis (A+B–) host phenotype is a factor with familial clustering for increased risk of Helicobacter pylori‐related non‐cardiac gastric cancer

The purpose of the present study was to test whether host erythrocyte Lewis phenotypes correlated with the risk of gastric cancers. Because of the association of gastric cancer with familial clustering, cancer relatives were investigated as to whether they had unique distribution of Lewis phenotypes. The study prospectively enrolled 74 Helicobacter pylori-positive gastric cancer patients and 100 H. pylori-positive duodenal ulcer patients to serve as non-cancer controls after panendoscopy. In addition, 433 family members from the 74 index cancer and 100 non-cancer control patients were enrolled. All enrolled cases were checked for their H. pylori status and erythrocyte Lewis phenotypes, defined as Le(a-b-), Le(a-b+), Le(a+b-), and Le(a+b+) subtypes by the anti-Le(a) and anti-Le(b) monoclonal antibodies. These H. pylori-infected patients with gastric cancer had a higher rate of Le(a+b-) phenotype and a lower rate of Le(a-b+) phenotype than the non-cancer duodenal ulcer controls (20.3% vs 9%; 51.4% vs 72%, P < 0.05). Among these H. pylori-infected patients, the risk of the patients with Le(a+b-) phenotype having gastric cancer was 3.15-fold higher as compared with those with the Le(a-b+) phenotype (P = 0.02, 95% confidence interval: 1.26-7.87). The offspring and cousins of the cancer patients had a higher rate of Le(a+b-) phenotype as compared to either that of the spouses of cancer index patients or to that of the family members of the non-cancer control (P < 0.05). Le(a+b-) phenotype of the H. pylori-infected host could be a risk factor (with familial clustering) for gastric carcinogenesis.

Clinical Outcomes of Eradication of Helicobacter pylori in Nonulcer Dyspepsia in a Population with a High Prevalence of Infection: Results of a 12-Month Randomized, Double Blind, Placebo-Controlled Study

Ninety-one Helicobacter pylori-positive patients with nonulcer dyspepsia were randomized to receive either lansoprazole, amoxicillin, and clarithromycin or lansoprazole and placebo. A validated questionnaire assessed dyspeptic symptoms at baseline and at 3, 6, and 12 months. Endoscopies and biopsies were performed at baseline and at 3 and 12 months. There was an overall trend, although not statistically significant, for a benefit of H. pylori eradication. Of the patients in the antibiotics group, 16 of 46 (35%) had symptomatic improvement, versus 9 of 43 (21%) in the control group (P = 0.164). In a secondary analysis, it was found that of the patients without endoscopic gastric erosions, 15 of 34 (44%) in the antibiotics group and 5 of 33 (15%) of controls had symptomatic improvement (P = 0.015). Helicobacter pylori eradication did not prove to be clinically beneficial, although a tendency to symptomatic benefit was detected. Further studies are necessary to confirm the implications of endoscopic gastric erosions in these patients.

Poor metabolizer genotype status of CYP2C19 is a risk factor for developing gastric cancer in Japanese patients with Helicobacter pylori infection

Cytochrome P450 2C19 (CYP2C19) polymorphism has been associated with the development of lung, liver or oesophageal cancer by detoxification of carcinogen(s) or activation of procarcinogen(s). To clarify the association between CYP2C19 polymorphisms and gastric cancer development in Japanese. Methods : We determined CYP2C19 genotypes (CYP2C19*1, *2 and *3) in 111 Helicobacter pylori-positive patients with gastric cancer and 315 H. pylori-positive controls without gastric cancer consisting of patients with gastritis only or peptic ulcer. Frequencies of CYP2C19 genotypes and serum pepsinogen I and II levels, a biomarker of gastric atrophy, in the gastric cancers and controls were compared. Frequencies of homozygous extensive metabolizers, heterozygous extensive metabolizers and poor metabolizers were 31.5%, 42.3% and 26.2% in the gastric cancers and 38.1%, 47.0% and 14.9% in the controls, respectively (P = 0.046). Poor metabolizers were associated with an increased risk for developing gastric cancer with the age- and sex-adjusted odds ratio (OR) of 1.975 [95% confidence interval (CI): 1.068-3.649], especially for diffuse type (OR: 3.385, CI: 1.187-9.648). There is no significant association between CYP2C19 genotypes and serum pepsinogen I level or pepsinogen I/II ratios, although serum pepsinogen I level in gastric cancers were significantly decreased. In H. pylori-positive Japanese, poor metabolizers of CYP2C19 appear to be at an increased risk for developing gastric cancer, especially diffuse type, and may require an intensive follow-up for scrutinizing possible gastric cancer development.

Low‐dose rabeprazole, amoxicillin and metronidazole triple therapy for the treatment of Helicobacter pylori infection in Chinese patients

Rabeprazole in combination with amoxicillin and metronidazole (RAM) has been shown to be an effective second-line treatment of Helicobacter pylori infection. The effects were compared of 7-day low-dose and high dose rabeprazole in RAM for the primary treatment of H. pylori infection in Chinese patients. Helicobacter pylori-positive dyspeptic patients were randomized to receive either (i) rabeprazole 10 mg, amoxicillin 1000 mg and metronidazole 400 mg (RAM-10) or (ii) high-dose rabeprazole 20 mg, amoxicillin 1000 mg and metronidazole 400 mg (RAM-20), each given twice daily for 7 days. Helicobacter pylori eradication was confirmed by (13)c-urea breath test 5 weeks after stopping medications. side-effects of treatments were documented. A total of 120 patients were eligible for analysis. By intention-to-treat and per-protocol analysis, the eradication rates were 83% and 86% in the RAM-10 group and 75% and 76% in the RAM-20 group, respectively (P = 0.26 and P = 0.17). Both regimens were well-tolerated and compliance was >98% in both groups. Low-dose rabeprazole in combination with amoxicillin and metronidazole is an effective, economical and well-tolerated therapy for the treatment of H. pylori infection in Chinese population.

Invasive and non-invasive diagnosis of Helicobacter pylori-associated atrophic gastritis: A comparative study

Objective. Helicobacter pylori-associated atrophic gastritis is known to be a significant risk factor for gastric cancer. Among the well-known parameters of atrophic gastritis are the levels of serum gastrin-17 (G-17) and pepsinogen I (PG1), which are biomarkers of gastric antral and corpus mucosal activity, respectively. The aim of study was to compare the production of G-17 and PG1 in patients with or without stomach mucosal atrophy and to investigate the utility of serum PG1 and/or G-17 concentrations for the objective evaluation of atrophic gastritis. Material and methods. . A total of 178 dyspeptic Helicobacter pylori-positive patients underwent diagnostic upper gastrointestinal endoscopy with biopsy. The degree of histologic gastric mucosal atrophy was compared with the fasting levels of PG1, and to the postprandial levels of G-17 detected by enzyme immunoassay. Results. . A decrease in serum G-17 levels along with worsening of the antral atrophy was observed; the serum levels of PG1 were reduced during progression of the corpus atrophy. In the multifocal atrophic gastritis, values for PG1 and G-17 serum concentrations were significantly lower than the respective cut-off values. Statistical analysis revealed statistically significant differences between the serum levels of PG1 and G-17 measured at different stages of stomach mucosal atrophy. Conclusions. A strong reverse correlation was found between histologic/endoscopic antral atrophy and serum G-17 levels, and between corpus atrophy and serum PG1 levels.

Helicobacter pyloriupregulates prion protein expression in gastric mucosa: A possible link to prion disease

Pathological prion protein (PrP(sc)) is responsible for the development of transmissible spongiform encephalopathies (TSE). While PrPc enters the organism via the oral route, less data is available to know about its uptake and the role of gastrointestinal inflammation on the expression of prion precursor PrPc, which is constitutively expressed in the gastric mucosa. We studied PrPc expression in the gastric mucosa of 10 Helicobacter pylori-positive patients before and after successful H pylori eradication compared to non-infected controls using RT-PCR and Western blotting. The effect of central mediators of gastric inflammation, i.e., gastrin, prostaglandin E(2) (PGE(2)), tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1beta) on PrPc expression was analyzed in gastric cell lines. PrPc expression was increased in H pylori-infection compared with non-infected controls and decreased to normal after successful eradication. Gastrin, PGE(2), and IL-1beta dose-dependently upregulated PrPc in gastric cells, while TNF-alpha had no effect. H pylori infection leads to the upregulation of gastric PrPc expression. This can be linked to H pylori induced hypergastrinemia and increased mucosal PGE(2) and IL-1beta synthesis. H pylori creates a milieu for enhanced propagation of prions in the gastrointestinal tract.

Effects of Helicobacter pylori Eradication on Platelet Activation and Disease Recurrence in Patients with Acute Coronary Syndromes

Platelet activation is consistently observed in animal models of Helicobacter pylori infection and could help to explain the alleged epidemiological association between H. pylori and coronary heart disease. Ninety-two patients with recent acute coronary syndromes were enrolled. Helicobacter pylori-positive patients were randomized to receive a 7-day course of omeprazole, amoxycillin and metronidazole or placebos. Two months later, H. pylori status was reassessed and baseline parameters, including soluble P-selectin and platelet surface expression of CD62P, CD63 and CD41, were measured again. Patients were followed-up for 1 year or until death or readmission. No baseline differences were observed between H. pylori-positive and -negative cases. Among H. pylori-positive patients, 18 received placebo and 31 received active medication resulting in eradication in 21 cases. No differences were observed in inflammatory parameters or platelet activation markers between patients with persistent or resolved H. pylori infection. However, coronary events recurred at 6 and 12 months, respectively, in 35% and 55% of patients with persisting H. pylori infection compared with 10% and 25% of patients in whom H. pylori was either absent or eradicated (p = .01). Only final H. pylori status [RR 3.07 (95% CI 1.35-98)] and number of coronary risk factors [RR 2.58 (95% CI 1.51-4.41)] were independent predictors of recurrence. Infection with H. pylori does not induce significant platelet activation in patients treated for coronary disease. Helicobacter pylori-infected patients, however, may have an increased risk of recurrence of coronary events.

Do procalcitonin and C-reactive protein levels have a place in the diagnosis and follow-up of Helicobacter pylori infections?

The aims of this study were to determine the levels of procalcitonin (PCT) and C-reactive protein (CRP) in Helicobacter pylori-positive (HP+) patients diagnosed with duodenal and gastric ulcer and to evaluate the correlation of PCT and CRP levels with other invasive and non-invasive diagnostic methods for determination of H. pylori eradication in post-treatment follow-up. Thirty-five HP+ patients with dyspepsia were included in this study. Serum samples (5 ml) were collected at admission and after 24 h. Antimicrobial therapy (omeprazole, amoxycillin and clarithromycin) was given for 1 week to HP+ patients who were positive only by culture or by urease test plus pathology. After 1 month, serum samples (5 ml) were collected again and culture, urease and pathology investigations were performed on endoscopic samples. PCT and CRP levels were measured in the collected blood samples. Thirty-five H. pylori-negative (HP-) cases with dyspepsia, 38 cases with bacteraemia and 35 healthy blood donors were included in this study as control groups. The mean and minimum-maximum levels of PCT were 1.39 (0.25-6.75), 0.35 (0.12-0.71), 7.45 (0.68-51.5) and 0.40 (0.12-0.71) ng ml(-1) for the groups of HP+, HP- and bacteraemia patients and healthy donors, respectively. Mean CRP levels were 1.00 (<0.5-8.11), 0.62 (<0.5-3.2), 11.5 (3.2-43.5) and 0.63 (<0.5-5.46) mg dl(-1) for the same groups. A statistically significant difference was found between HP+ patients and both HP- cases and healthy blood donors for PCT levels, and higher PCT levels were found on admission in cases of bacteraemia than in the other groups (P < 0.05). PCT levels of HP+ cases decreased significantly (from 1.39 to 0.86) between admission and the post-treatment period (30 days); however, PCT levels remained higher than the cut-off value (0.5 ng ml(-1)). Similar ranges of CRP levels were found over the same time-period. The sensitivity of PCT was found to be higher than that of CRP on admission, but the specificity of PCT was found to be lower than that of CRP on the day of admission (65 and 74%, respectively). The sensitivity of PCT was the same as that of CRP for the post-treatment period, but specificity of PCT was higher than that of CRP for the post-treatment period (83 and 76%, respectively). It was concluded that PCT and CRP are not very effective markers for H. pylori infection in primary diagnosis or in eradication follow-up after therapy when used in parallel with conventional diagnostic methods, even if there is a difference in PCT and CRP levels between HP+ and HP- cases on admission.

P0276 HOW DOES HELICOBACTER PYLORI INFECTION IS INFLUENCED BY IMMUNOSUPPRESSIVE THERAPY?

Introduction: Helicobacter pylori (HP) infection is an important agent in gastric metaplasia/cancer and gastrointestinal lymphoma, which is observed in higher rate under immunosuppressive therapy. Adhesion molecules and proliferation factors play a significant role in this disorders, however, there is no data of those in children with HP infection after kidney transplantation (NTX). Moreover, the prevalence of HP infection in children after NTX is also unknown. Thus, we investigated the prevalence of HP, and the expression of ICAM-1 and Ki-67 proliferation marker in the antral mucosa of children with HP infection under immunosuppressive therapy. Methods: C13-urea breath test was performed to screen HP infection. 22 NTX patients (mean age, 16.1 y, male,12) were enrolled in our study. ICAM-1 and Ki-67 expressions were determined by means of immunohistochemistry. To compare data of NTX+HP, two types of controls were involved, HP positive and HP negative controls. Results: C13-urea breath test was positive in 5/22 children (23%) indicating higher incidence for HP infection than in controls (1/22, 4,5%). Two out of five HP positive patients had no gastrointestinal complaints, however, all biopsies showed chronic antral mucosal inflammation with the presence of HP. We found significantly increased expression of ICAM-1 in children with NTX+HP and HP infection when compared with HP negative controls (median, 7,2%, 7,3%, 3,2%, respectively). The highest crypt proliferation rate was found in NTX+HP in comparison to both HP+ and negative controls (median, 22,2%, 17,1%, 5,3%, respectively). The surface enterocytes showed complete absence of ICAM-1 expression indicating that antigen presentation and induction of co-stimulatory signals mainly occur in the lamina propria. Conclusion: We found high incidence in HP infection of children under immunosuppressive drugs following NTX, even in absence of gastrointestinal symptoms. Increased crypt proliferation rate observed in NTX may indicate a risk for gastric metaplasia. Based on these, our findings indicate to screen for HP in children after kidney-transplantation.

Traitements curatif et préventif des ulcères gastro-duodénaux induits par les AINS

The use of treatments to heal or to prevent nonsteroidal anti-inflammatory drugs (NSAIDs) associated gastroduodenal lesions is based on replacement of mucosal prostaglandin deficiency or inhibition of acid secretion. Four-week acid suppression by proton pump inhibitors (PPI) with 7-day eradication triple therapy in Helicobacter pylori positive patients is effective in healing gastric and duodenal ulcer upon discontinuation of NSAIDs. In the event NSAIDs must be continued, PPIs (omeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg) are more effective than H2-blockers and cytoprotective agents (sucralfate, misoprostol) to heal mucosal lesions. In long-term prevention studies, omeprazole 20 mg, lansoprazole 15 mg, and pantoprazole 20 mg significantly reduce gastric and duodenal ulcer rates. Misoprostol 800 microg is as effective as PPIs for preventing symptomatic and complicated gastric ulcers, but less effective to prevent duodenal ulcer, with a high rate of adverse effects such as diarrhea. Helicobacter pylori eradication in infected patients decrease the risk of NSAIDs-associated lesions but is less effective than concomitant antisecretory treatment. Current data from comparative studies of PPIs vs ranitidine or misoprostol are in favor of the PPIs as well tolerated and effective drugs in the prophylaxis of NSAIDs-related gastroduodenal lesions in high-risk patients.

Helicobacter pylori infection and increased nitrite synthesis in the stomach : Inflammation and atrophy connections

Background. We have previously shown that the nitrite content in the gastric juice of Helicobacter pylori-positive patients is significantly higher than that of H. pylori-negative patients and it decreases after eradication of H. pylori. Aim. To examine the relationship between the nitric oxide synthesis in the gastric lumen and histological findings. Methods. Eighty-five middle aged Japanese patients were studied. Four specimens, each obtained from the greater and lesser curvature of antrum and gastric body were processed for the determination of histopathological scores using the updated Sydney System. Gastric juice was collected endoscopically to determine the concentration of nitrite using a modified Griess reaction. Results. There was a significant positive correlation between the nitrite and the pH levels ( r=0.81, P<0.001) and between the pH levels and the histopathological scores in the corpus. The gastric juice pH and concentration of the nitrite increased in patients with histological diagnosis of normal, antral-predominant gastritis, pangastritis and corpus-predominant gastritis in due order. Conclusions. H. pylori infection effects nitric oxide synthesis in the gastric lumen which is mainly connected with hypoacidity. The gastric juice pH is one of the useful markers for corpus dominant gastritis and probably for high-risk group of gastric cancer.

142 Phase II study of imatinib mesylate in salivary gland adenoid cystic carcinoma

Background. Pernicious anaemia is associated with atrophic body gastritis and considered an autoimmune disease. Whether Helicobacter pylori is involved in the induction of pernicious anaemia is uncertain.Aims. To investigate the prevalence of Helicobacter pylori infection in pernicious anaemia patients and to ascertain whether the Helicobacter pylori positive patients had distinctive clinical and gastric morphofunctional characteristics.Patients and Methods. A series of 81 consecutive pernicious anaemia patients underwent serological, functional and endoscopic/histological investigations.Results. A total of 49 (60.5%) patients were Helicobacter pylori-positive (males 61.2% vs females 38.8%). No difference was observed in clinical and morphofunctional characteristics between Helicobacter pylori-positive and negative patients, whereas distinctive functional/histological features between histologically Helicobacter pylori-positive (n=8) and serologically Helicobacter pylori-positive (n=41) cases were detected. In the histologically Helicobacter pylori-positive group, Pepsinogen I was higher [13 [0–58] vs 5 [0–26] ng/ml; p=0.0025]) and positivity for anti-parietal cell antibodies was lower [42.9% vs 76.9, p=0.0867). Antral histological variables of the gastritis score were significantly higher in the histologically Helicobacter pylori-positive than in the serologically Helicobacter pylori-positive patients, but this latter group had a higher score of body atrophy (2.63± 0.12 vs 1.71 ± 0.29; p=0.0051). Body inflammation was also significantly higher in the histologically Helicobacter pylori-positive group (chronic inflammation: 1.43±0.2 vs 1.05±0.06; p=0.0271; inflammation acitivity:: 0.57±0.3 vs 0.15±0.06, p=0.0220). Antral mucosa was normal in 2441 (58.5%) of the serologically Helicobacter pylori-positive patients, but only in 18 (12.5%) of the histologically Helicobacter pylori-positive patients (p=0.232).Conclusions. Almost two thirds of pernicious anaemia patients have evidence of Helicobacter pylori, but only those with an active Helicobacter pylori infection have distinctive functional and histological features. These findings support the hypothesis that Helicobacter pylori infection could play a triggering role in a subgroup of pernicious anaemia patients.

Endoscopic 13C-urea breath test for the diagnosis of Helicobacter pylori infection

Background. Endoscopic 13C-urea breath test may avoid contamination of oral urease and rapidly discriminate Helicobacter pylori-positive and Helicobacter pylori-negative patients. Aims. To compare the accuracy of endoscopic 13C-urea breath test with conventional invasive methods in diagnosis of Helicobacter pylori infection. Patients. One hundred patients who attended for routine upper gastrointestinal endoscopy were included. Methods. 13C-urea was applied to the stomach through the working channel of endoscope at the end of endoscopic examination. Breath samples were collected before endoscopy and 2, 4, 6, 8, 10 min after consumption of 100 or 50 mg 13C-urea. Helicobacter pylori infection was defined as those with positive culture or positive results of both histology and CLO test. Results. The accuracy of 100 mg endoscopic 13C-urea breath test was significantly higher than that of culture and CLO test (100% vs. 88% and 92%, p=0.02 and 0.03, respectively). The accuracy of 50 mg endoscopic 13C-urea breath test was higher than that of histology and CLO test (98% vs. 90% and 96%, respectively), although the differences were not statistically significant. Conclusions. Endoscopic 13C-urea breath test has a higher accuracy compared with biopsy-based modalities. It may be a good choice to diagnose Helicobacter pylori infection if endoscopy is indicated for a dyspeptic patient.

Tumor Necrosis Factor Alpha and Apoptosis in Helicobacter pylori Related Progressive Gastric Damage: A Possible Mechanism of Immune System Involvement in Epithelial Turnover Regulation

Helicobacter pylori (HP) related inflammation is mediated by tumour necrosis factor alpha (TNFα), which “in vitro” increases epithelial apoptosis in response to infection. In the early stages of HP gastritis, a raised epithelial apoptosis occurs; this phenomenon becomes less evident with progression towards intestinal metaplasia. Aim of our study was to analyze “in vivo” mucosal TNFα in relation to epithelial apoptosis in the progression of HP related histological damage. Antral biopsies from 20 HP positive patients were retrospectively studied: 10 with and 10 without intestinal metaplasia (IM and CG group respectively); samples of 10 dyspeptics with normal HP negative stomach (N) were used as control. The following parameters were evaluated by immunohistochemistry: 85 kDa caspase-cleaved fragment (p85) of human poly (ADP-ribose) polymerase (PARP) labelling index (LI) as marker of apoptosis and TNFα LI in stromal cells as marker of inflammatory response. Both epithelial apoptosis and mucosal TNFα expression were higher in chronic active gastritis compared to intestinal metaplasia and controls (PARP and TNFα LI: CG>IM>N; ANOVA & Student-Neumann-Keuls; p<0.05 and p<0.01, respectively). Pearson' s coefficient showed a significant correlation between PARP and TNFα LI in IM and CG groups. Our data show that mucosal TNFα, similarly to what suggested “in vitro”, may be related “in vivo” to epithelial apoptosis thus suggesting a possible mechanism for immune system involvement in the control of gastric epithelial turnover.

Serum positive cagA in patients with non-ulcer dyspepsia and peptic ulcer disease from two centers in different regions of Turkey.

To investigate and compare frequencies of serum positive cagA in patients from two separate regions of Turkey who were grouped according to the presence of peptic ulcer disease or non-ulcer dyspepsia. One hundred and eighty Helicobacter pylori-positive patients with peptic ulcer disease or non-ulcer dyspepsia were included in the study. One hundred and fourteen patients had non-ulcer dyspepsia and 66 had peptic ulcer disease (32 with gastric ulcers and/or erosions and 34 with duodenal ulcers). Each patient was tested for serum antibody to H. pylori cagA protein by enzyme immunoassay. The total frequency of serum positive cagA in the study group was 97.2 %. The rates in the patients with peptic ulcers and in those with non-ulcer dyspepsia were 100 % and 95.6 %, respectively. These results were similar to those reported in Asian studies, but higher than those that have been noted in other studies from Turkey and Western countries. The high rates of serum positive cagA in these patients with peptic ulcer disease and non-ulcer dyspepsia were similar to results reported in Asia. The fact that there was high seroum prevalence regardless of ulcer status suggests that factors other than cagA might be responsible for ulceration or other types of severe pathology in H. pylori-positive individuals.

Eradication therapy for peptic ulcer disease in Helicobacter pylori positive patients.

Peptic ulcer disease is the cause for dyspepsia in about 10% of patients. 95% of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori. Eradication of H pylori reduces the relapse rate of ulcers but the magnitude of this effect is uncertain. The primary outcomes were the proportion of peptic ulcers healed initially and proportion of patients free from relapse following successful healing. Eradication therapy was compared to placebo or pharmacological therapies in H. pylori positive patients. Secondary aims included symptom relief and adverse effects. A search was undertaken according to the Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group module using CCTR, MEDLINE, EMBASE and CINAHL databases. Experts in the field and pharmaceutical companies were contacted. Abstract books between 1994 and 2002 were hand-searched. Randomised controlled trials of short and long-term treatment of peptic ulcer disease in H. pylori positive adults were analysed. Patients received at least one week of H pylori eradication compared with ulcer healing drug, placebo or not treatment. Trials were included if they reported assessment from 2 weeks onwards. Data were collected on ulcer healing, recurrence, relief of symptoms and adverse effects. 59 trials were eligible. Data extraction was not possible in 7 trials, and 52 trials were included. In duodenal ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34 trials, 3910 patients, relative risk [RR] of ulcer persisting = 0.66; 95% confidence interval [CI] = 0.58, 0.76) and no treatment (2 trials, 207 patients, RR = 0.37; 95% CI 0.26, 0.53). In gastric ulcer healing, no significant differences were detected between eradication therapy and UHD (13 trials, 1469 patients, RR = 1.32; 95% CI = 0.92, 1.90). In preventing duodenal ulcer recurrence no significant differences were detected between eradication therapy and maintenance therapy with UHD (4 trials, 319 patients, relative risk [RR] of ulcer recurring = 0.73; 95% CI = 0.42, 1.25), but eradication therapy was superior to no treatment (26 trials 2434 patients, RR = 0.19; 95% CI = 0.15, 0.26). In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment (9 trials, 774 patients, RR = 0.31; 95% CI 0.19, 0.48). A 1 to 2 weeks course of H. pylori eradication therapy is an effective treatment for H. pylori positive peptic ulcer disease.

Interleukin 1β polymorphisms increase risk of hypochlorhydria and atrophic gastritis and reduce risk of duodenal ulcer recurrence in Japan

Background & Aims: Interleukin-1 beta (IL-1β) polymorphisms are associated with increased risk of gastric cancer in whites. This study aimed to examine effects of these polymorphisms on gastric acid secretion, atrophic gastritis, and risk of peptic ulcer in Japan. Methods: We determined IL-1B-511/-31 and IL-1RN genotypes and measured gastric juice pH, serum pepsinogen (PG) I and II levels, and gastritis and atrophy scores in Helicobacter pylori–positive patients with gastritis only, gastric ulcers, or duodenal ulcers (DUs), and H. pylori–negative controls. Results: In the H. pylori–positive group, subjects with the proinflammatory IL-1B-511 T/T genotype had the highest atrophy and gastritis scores, the highest median gastric juice pH, and the lowest median serum PG I/PG II ratios. Although gastric juice pH significantly increased and serum PG I and PG I/PG II ratios significantly decreased in the IL-1B-511 T/T genotype group with age, no such age-dependent changes were observed in the C/C genotype group. Changes in the C/T genotype group were intermediate. In the H. pylori–negative group, the IL-1 loci had no effect on any of the physiologic or morphologic parameters. Carriage of IL-1RN allele 2 significantly protected against DU disease while the IL-1B-511 T/T genotype significantly protected against DU recurrence in patients older than 60 years. Conclusions: Proinflammatory IL-1β polymorphisms are associated with hypochlorhydria and atrophic gastritis in Japan. The effects are dependent on H. pylori infection and become more significant with advancing age. This may explain the high incidence of gastric cancer in Japan and also the age-dependent decrease in DU recurrence in infected subjects.GASTROENTEROLOGY 2002;123:92-105

CYP2C pharmacogenetics and tailor-made therapeutic implications

Four CYP2C (2C8, 2C9, 2C18 and 2C19) gene products have been expressed in human liver. Among them both CYP2C9 and 2C19 have been extensively studied in different ethnic groups, showing an interethnic difference in the incidence of the poor metabolizers (PMs). Asian populations are characterized by the lower frequency of the CYP2C9 poor metabolizers and by the greater frequency of the CYP2C19 poor metabolizers compared with Caucasian populations, respectively. Clinically important drugs are metabolized by either of CYP2C isoforms as follows: S-warfarin, phenytoin and sulfonylurea antidiabetics by CYP2C9 and proton pump inhibitors (PPIs), diazepam and imipramine by CYP2C19. This review focuses on the therapeutic implications of CYP2C9 and 2C19 pharmacogenetics (or pharmacogenomics) based upon the recent relevant literature sources. Lastly, this reviewer will propose a pharmacogenetic-based tailor-made therapeutic strategy by exemplifying our recent data on CYP2C19 genotype status versus cure rates of Helicobacter pylori-positive peptic ulcer patients undergoing dual or triple therapy with a PPI and antibiotic(s).

Eradication of Helicobacter pylori may be beneficial in the management of chronic open-angle glaucoma.

We have documented a high prevalence of Helicobacter pylori infection in patients with glaucoma. To evaluate the effect of H pylori eradication on the 2 most commonly used glaucoma parameters: intraocular pressure and visual field. A total of 41 patients with glaucoma and 30 age-matched anemic controls underwent upper gastrointestinal endoscopies and gastric mucosal biopsies to detect the presence of H. pylori infection by histologic analysis and rapid urease test (CLOtest; Delta West, Draper, Utah). Saliva samples were also tested by CLOtest. Serum anti-H pylori-specific IgG was analyzed by enzyme-linked immunosorbent assay. Helicobacter pylori-positive patients received a triple eradication regimen (omeprazole, clarithromycin, and amoxicillin treatment), and all patients were observed for 2 years while remaining under the same antiglaucoma therapy. Helicobacter pylori was detected in 88% of glaucoma cases and in 47% of controls (P<.001). Helicobacter pylori eradication was successful in 83% of treated patients. At the 2-year clinical end point, glaucoma parameters (mean intraocular pressure and mean visual field parameters) were improved in the subgroup of patients where H. pylori eradication was successful (P<.001 for intraocular pressure; P< or =.01 for visual field parameters), but not in the other patients. Helicobacter pylori eradication may positively influence glaucoma parameters, suggesting a possible causal link between H pylori and glaucoma.