Extragastric diseases associated with Helicobacter pylori infection

This paper critically reviews the current literature on extragastric diseases associated with Helicobacter pylori infection, with an emphasis on methodologic issues that complicate interpretation of study findings. This review reveals common study limitations and overall uncertainty that H. pylori infection plays a role in extragastric diseases, although such a role has not been clearly ruled out for specific diseases of relevance. Evidence suggests that anti-H. pylori therapy may lead to improvement of a few extragastric diseases, in particular, idiopathic thrombocytopenic purpura, iron deficiency anemia, and chronic idiopathic urticaria, but the data from randomized controlled trials are insufficient to confirm this beneficial effect; if the benefit of anti-H. pylori therapy for specific diseases is real, it is not clear if it results from removing H. pylori-specific injurious effects, eliminating some other infectious pathogen, or reducing the total infectious burden.     

Helicobacter pylori infection and precancerous lesions of the stomach

H. pylori infection is associated with a slightly increased risk of gastric cancer. However, the risk is much higher in the subgroup of infected patients who have atrophic gastritis and extensive intestinal metaplasia. In those subjects, H. pylori acts as a trigger of the sequence which begins as atrophic gastritis with intestinal metaplasia and evolves towards immature forms of intestinal metaplasia and dysplasia. It seems that factors different from H. pylori (diet, genetical background, etc.) might have an influence on how often gastric precancerous lesions appear in H. pylori-infected subjects. Effective prevention of gastric carcinoma would require identification of the patients at risk in an early step of the process. Preventive measures would include H. pylori eradication and changes in the diet (i.e., increase of vitamin C and carotenoid intake). Preliminary data suggest that H. pylori eradication cannot revert intestinal metaplasia. However, it is possible that eradication of the bacteria would prevent progression towards immature forms of intestinal metaplasia and dysplasia.     

Helicobacter pylori infection among offspring of patients with stomach cancer

BACKGROUND & AIMS: A positive family history is associated with an increased risk of stomach cancer. We compared the prevalence of Helicobacter pylori infection, a known risk factor for stomach cancer, between subjects with and without parental history of stomach cancer to evaluate a potential role of H. pylori infection in familial aggregation of stomach cancer. METHODS: A total of 1351 men and women aged 30-74 years who participated in the German Health and Nutrition Survey conducted in the western part of Germany in 1987-1988 were included in the study. Detailed information on sociodemographic factors, nutritional factors, and parental history of cancer was obtained by standardized interviews. Serum samples were analyzed for immunoglobulin G antibodies against H. pylori by enzyme-linked immunosorbent assay. RESULTS: The prevalence of H. pylori infection was much higher (69%) among subjects with a parental history of stomach cancer than among other subjects (44%). This association persisted after control for potential confounders by multiple logistic regression (adjusted odds ratio, 2.7; 95% confidence interval, 1.3-5.9), and was particularly strong among subjects below age 55 (adjusted odds ratio, 5.1; 95% confidence interval, 1.6-16.1). CONCLUSIONS: These results suggest that familial aggregation of stomach cancer may be explained at least partly by familial clustering of H. pylori infection.     

Diagnosis of Helicobacter pylori infection and diseases associated with Helicobacter pylori by Helicobacter pylori outer membrane proteins

sAIM: To examine the serological response of patients with upper gastrointestinal diseases and Helicobocter pylon (Hpy/on)infection to two Hpyloriouter membrane proteins (OMPs) (Mr18 000 and Mr26 000) acquired by gene recombinant technique, and to determine the diagnostic significance of serological tests derived from these OMPs.METHODS: Recombinant vectors encoding the two Hpylori OMPs were used to transform and express in BL21 (DE3) E.coli After purification with NP-NTA agarose resin, colloid gold kits were prepared with purified recombinant proteins to detect H pyloH infection and H pylori-associated diseases by the immunity-marker technology. We selected 150 patients with Hpy/on‘infection and digestive symptoms wibhout previous treabnent, including chronic gastritis (n = 60), duodenal ulcer (n = 30), gastric ulcer (n = 30), and gastric cancer (n=30).As controls, 33 Hpylori-negative healthy volunteers were also recruited. Serum samples were collected from all subjects, and the antibodies to specific proteins of Hpylori were tested with the colloid gold test kits. The sensitivity,specificity and accuracy of the colloid gold tests were evaluated, by using the combination of standard diagnostic methods (^13C urea breath test and bacteria culture) and classic enzyme-linked immunosorbent assay (ELISA) as reference.RESULTS: After purification with Ni^2+-NTA agarose resin,the purity of recombinant fusion proteins was about 95%.The recombinant fusion proteins were recognized by the specific monodonal antibodies against bhe two Hpy/oriOMPs,as demonstrated by the ELISA. Of the 150 serum samples from patients infected with Hpy/oH 141 (94.0%) responded positively to the recombinant protein with Mr26 000, while the seropositive rates were 95.0%, 96.7%, 96.7% and 90.0% for patients with H pylori-associated chronic gastritis,duodenal ulcer, gastric ulcer, and gastric cancer respectively.The sensitivity, specificity, and accuracy of the colloid gold kit with Mr26 000 protein were 94.0%, 97.0%, and 94.5%,respe.ctively. Compared with the classic ELISA, bacteria culture and ^13C urea breath test results in detecting Hpyloriinfection, there was no significant difference (P>O.O5). For the colloid gold kit with Mr18 000, the seropositive rates were 52.0%, 40.0%, 40.0%, 53.3% and 86.7%, respectively,in Hpylori-infected palJents, and bhose wibh Hpylori-associated chronic gastritis, duodenal ulcer, gastric ulcer, and gastric cancer. There was a significant difference (P<0.05) in seropositivity between patient with gastric cancer (86.7%) and those with other diseases (43.3%).CONCLUSION: The two colloid gold kits derived from the recombinant OMPs are useful tools either for detecting Hpyloriinfection, or for, predicting Hpylori-associated gastric malignancy.     

Pathogenesis of Helicobacter pylori infection]

Helicobacter pylori (H. pylori), a long term colonizer of human stomach is known to infect a half of mankind. Gastric and duodenal ulcer, gastric adenocarcinoma and MALT lymphoma develop in a subset of infected individuals. Pathogenesis of H. pylori infection is based on the long-term host to bacterial interaction and affected by the virulence factors of the bacterium, environmental and host factors (age, sex, blood type). Mucosal inflammation is the basic principle mechanism underlying the disease development in which tissue destruction may be initiated and maintained by both the bacterial toxins (CagA, VacA, LPS) and immune responses by the host. Immune evasion with bacterial modulation of host response affects the long-term host colonization. Colonization is also affected by urease and/or motility of the bacterium, presence of lipopolysaccharide (LPS) and various bacterial enzymes. Gastric mucosal atrophy and intestinal metaplasia can develop during the course of H. pylori infection predisposing to carcinogenesis. Host cytokine gene polymorphism would be the one explanation for host susceptibility to peptic ulcer or gastric cancer. Investigation into the pathogenesis of H. pylori related diseases could provide an answer to the impact of chronic host to microbial interaction resulting human diseases.     

Diagnosis of Helicobacter pylori infection]

Helicobacter pylori (H. pylori) infection can be diagnosed either by invasive techniques requiring endoscopy and biopsy (histological examination, culture, polymerase chain reaction) and or noninvasive techniques (urea breath test, serology, urine or blood, detection of H. pylori antigen in stool specimen). At present, no single test can be absolutely sufficient to detect the colonization by H. pylori, and a combination of above two tests is recommended if feasible. Because all the tests have their pitfalls and limitations, the choice of tests should depend on the clinical circumstances, the likelihood ratio of positive and negative tests, the cost-effectiveness of the testing strategy, and the availability of the tests. It is important to know which test in a certain clinical setting gives the best outcome. Some clinical circumstances warrant invasive studies, principally in patients with alarm symptoms (bleeding, weight loss, etc.) as well as older patients with new-onset dyspepsia. Endoscopy may also be advisable in patients who have failed eradication therapy and need culture to examine antimicrobial sensitivity testing to determine appropriate regimen. Recent Western studies have also demonstrated that a strategy of 'test and treat' for H. pylori in uninvestigated, young (<45 years), dyspeptic patients in primary care is safe and reduces the need for endoscopy. Therefore, it is necessary to hold a second consensus meeting for the diagnosis and treatment of H. pylori infection in Korea for the renewal of clinical guidelines in primary, secondary, and tertiary care based an evidence-based analysis.     

Treatment of Helicobacter pylori infection]

Significant progress and new insights have been gained since Helicobacter pylori was found in 1982. Even with currently most effective treatment regimen, about 10-20% of patients will fail to obtain the eradication of H. pylori infection. This review will focus on the empirical treatment for H. pylori infection in Korea. Seven days triple therapy (proton pump inhibitor, amoxicillin and clarithromycin) has been the main first line therapy for H. pylori infection in Korea after the recommendation by Korean H. pylori study group in 1998. Such triple therapy has been the effective regimen for eradication of H. pylori infection. However, the efficacy of 7 days proton pump inhibitor-amoxicillin-clarithromycin therapy becomes lower and various eradication rates probably reflects the increase in antimicrobial resistance, recently. The recent multi-center prospective randomized study and meta-analysis showed 14 days proton pump inhibitor-amoxicillin-clarithromycin therapy is more effective than 7 days or 10 days therapy. In the case of failure, quadruple therapy (proton pump inhibitor, a bismuth salt, metronidazole and tetracycline) is a very effective second-line regimen. After the failure of two or more eradication treatments, bacterial resistance to antibiotics should be evaluated and the regimen of third-line therapy should be selected according to each antimicrobial susceptibility. The empirical third-line therapies, recommended in the cases that antimicrobial susceptibility test is unavailable, are unclear of its validity at present in Korea. The triple therapies including rifabutin, moxifloxacin, or levofloxacin or dual therapy including high dose proton pump inhibitor and amoxicillin are needed to be proven as possible candidates for the empirical third-line therapy. Multiple eradication failures should be handled on a case-by-case basis by specialists.     

幽门螺杆菌与胃癌关系的研究现状

幽门螺杆菌与胃癌关系的研究现状郭飞胡伏莲贾博琦幽门螺杆菌（Ｈｅｌｉｃｏｂａｃｔｅｒｐｙｌｏｒｉ，Ｈｐ）自分离出来迄今已有十几年的历史，大量的研究证明Ｈｐ是引起人类慢性胃炎的主要因素，且其与消化性溃疡密切相关，感染Ｈｐ的人群中，以消化性溃疡病的检出率最...     

Analysis of the urinary peptidome associated with Helicobacter pylori infection

AIM:To investigate the relationship between urinary peptide changes and Helicobacter pylori(H.pylori) infection using urinary peptidome profiling.METHODS:The study was performed in volunteers(n = 137) who gave informed consent.Urinary peptides were enriched by magnetic beads based weak cation exchange chromatography and spectrums acquired by matrix-assisted laser desorption/ionization time-of-flight(MALDI-TOF) mass spectrometry(MS).ClinProTools bioinformatics software was used for statistical analysis and t...     

Helicobacter pylori infection increases mucosal permeability of the stomach and intestine

It is important to study the effect of Helicobacter pylori infection on the permeability of the intestine. Permeability was evaluated by oral sucrose tolerance test using sucrose 25 g in 200 ml of water. Existence of H. pylori itself was associated with increased permeability of sucrose. Also, the permeability of sucrose increased as polymorphonuclear and lymphocyte infiltration increased. The increase of mucosal permeability suggests that antigens like protein penetrate into the body and result in systemic reactions. Thus, it is important to study the implication of increased permeability in relation not only to gastric diseases but also certain systemic diseases.     

Helicobacter pylori infection is associated with advanced colorectal neoplasia

A series of 186 patients treated for Crohn's disease during the period 1956 to 1968 has been followed up in 1970, 1975, and now in 1983. Among 173 patients operated on there were 89 recurrences (52%). After a follow-up time >14 years (mean, 18 years) ‘radical’ resections at the first operation gave a lower recurrence rate (31%), fewer reoperations, and a better quality of life compared with non-‘radical’ resections (recurrence rate, 83%). The quality of life estimated for all patients alive in 1983, 152 patients, was good in 89%; 8.6% had moderate subjective symptoms, and 2.6% had pronounced subjective symptoms. With an increasing follow-up time there was no decrease in the patients' quality of life. Ileorectal anastomosis did not give very good results; proctocolectomy and ileostomy, however, gave good results. Regular investigation of all patients is of vital importance to give them a good quality of life.