Proof of an association between Helicobacter pylori and idiopathic thrombocytopenic purpura in Latin America

BACKGROUND: Association between Helicobacter pylori and idiopathic thrombocytopenic purpura (ITP) has been found in Japan and in some European countries. It has also been shown that eradication of H. pylori can increase platelet counts in patients with ITP. The aims of this study were to determine the prevalence of H. pylori infection in patients with ITP in Colombia, and the effect of bacterial eradication on their platelet counts. MATERIALS AND METHODS: Between December 1998 and April 2006, a total of 32 patients diagnosed with ITP were included in the study. Controls were age and sex matched. RESULTS: H. pylori infection in patients with ITP was significantly higher (p = .00006) than in control individuals (90.6% and 43.8%, respectively), as determined by (13)C-urea breath test. A significant association between H. pylori infection and ITP was found (p < .0003), with an odds ratio (OR) of 13.15 (95%CI: 3.24-53.29). Multivariate analysis for the association between H. pylori and ITP showed an OR of 20.44 (95%CI: 3.88-107.49) for women and 19.28 (95%CI: 2.03-183.42) for individuals over 50 years. All 29 H. pylori-positive patients with ITP received eradication treatment. After a median follow up of 12.2 months, 80.8% had a recovery in platelet counts. CONCLUSIONS: According to these results and others from different countries where H. pylori infection rates are high, patients with ITP should be initially tested for H. pylori status, and if present, infection should be eradicated before initiating a drastic conventional ITP treatment. An algorithm for the study and management of patients with ITP in the post-Helicobacter era is presented.     

Helicobacter pylori vacA and cagA genotypes in patients from northeastern Brazil with upper gastrointestinal diseases

Helicobacter pylori causes chronic gastric inflammation and significantly increases the risk of duodenal and gastric ulcer disease and distal gastric carcinoma. In this study, we evaluated the Helicobacter pylori vacA and cagA genotypes in patients from a Brazilian region where there is a high prevalence of gastric cancer. Polymerase chain reaction (PCR) was used to investigate vacA mosaicism and cagA status in the gastric mucosa of 134 H. pylori-positive patients, including 76 with gastritis: 28 with peptic ulcer disease and 30 with gastric cancer. The s1m1 variant was the predominant vacA genotype observed, whereas the s1 allele was more frequently observed in patients with more severe diseases associated with H. pylori infection [p = 0.03, odds ratio (OR) = 5.72, 95% confidence interval (CI) = 1.15-38.60]. Furthermore, all of the s1 alleles were s1b. Mixed vacA m1/m2 strains were found more frequently in patients with gastric cancer and a cagA-positive status was significantly associated with gastric cancer (p = 0.016, OR = 10.36, 95% CI = 1.35-217.31). Patients with gastric cancer (21/21, 100%, p = 0.006) or peptic ulcers (20/21, 95%, p = 0.02) were more frequently colonised by more virulent H. pylori strains compared to gastritis patients (41/61, 67.2%). In conclusion, in the northeastern of Brazil, which is one of the regions with the highest prevalence of gastric cancer in the country, infection with the most virulent H. pylori strains, carrying the cagA gene and s1m1 vacA alleles, predominates and is correlated with more severe H. pylori-associated diseases.     

The effects of genetic polymorphisms of IL-1 and TNF-A on Helicobacter pylori-induced gastroduodenal diseases in Korea

OBJECTIVE: To evaluate whether or not genetic polymorphism of IL-1B, IL-1RN, and TNF-Alpha is an important factor in the different expression of gastroduodenal diseases after Helicobacter pylori infection. METHODS: This study consisted of 1360 subjects: control, gastric cancer (GC, intestinal type, and diffuse type), benign gastric ulcer (BGU), duodenal ulcer, and first-degree gastric cancer relative (GCR). IL-1Beta-511 and TNF-A-308 biallelic polymorphism were genotyped by 5' nuclease polymerase chain reaction (PCR) assays, and PCR-restriction fragment length polymorphism (PCR-RFLP). IL-1RN penta-allelic variable number of tandem repeats was genotyped by PCR. RESULTS: There was no difference in the genetic polymorphism of IL-1Beta-511, IL-1RN and TNF-A in the patients with gastric cancer regardless of H. pylori positivity compared with control. However, the frequencies of IL-1B-511 C/T (OR: 0.5, 95% CI: 0.3-0.7) and T carrier (OR: 0.6, 95% CI: 0.4-0.8) were lower in the H. pylori-positive BGU patients. The IL-1RN 2/2 was higher (OR: 5.5, 95% CI: 1.1-28.5) in the H. pylori-positive GCR. There was no significance in the polymorphism of TNF-Alpha-308 regardless of H. pylori-induced gastroduodenal diseases. CONCLUSIONS: The IL-1Beta-511 T-carrier polymorphism has a negative effect on the development of H. pylori-positive BGU, and high frequency of IL-1RN 2/2 was found in the H. pylori-positive relatives of GC patients, which suggest that this genetic polymorphism could play some role in the H. pylori-induced gastroduodenal diseases in Korea.     

复方嗜酸乳杆菌片治疗幽门螺杆菌感染的Meta分析

系统评价复方嗜酸乳杆菌片治疗幽门螺杆菌感染的有效性、安全性。

以“复方嗜酸乳杆菌片”“幽门螺杆菌感染”“Compound Eosinophil-Lactobacillus Tablets”“Helicobacter pylori infection”为主题词, 系统检索The Cochrane Library、PubMed、Springer、ProQuest、中国知网、万方和维普等数据库(建库-2020年5月)的随机对照试验文献。利用RevMan 5.3软件对复方嗜酸乳杆菌片的有效性、安全性进行Meta分析。

依据严格的纳入排除标准, 最终纳入18篇随机对照试验文献。Meta分析结果显示: 复方嗜酸乳杆菌片与一线治疗方案联合用药治疗幽门螺杆菌感染临床疗效更优[RR=0.84, 95%CI(0.80, 0.87), P < 0.000 01], 安全性更好[OR=2.83, 95%CI(2.30, 3.49), P < 0.000 01]。进一步亚组分析表明, 复方嗜酸乳杆菌片与四联疗法联合用药治疗幽门螺杆菌感染与四联疗法相比, 临床疗效更优[RR=0.88, 95%CI(0.83, 0.93), P < 0.000 01], 安全性更优[OR=2.58, 95%CI(1.92, 3.48), P < 0.000 01];复方嗜酸乳杆菌片联合三联疗法治疗幽门螺杆菌感染较三联疗法临床疗效更优[RR=0.81, 95%CI(0.76, 0.85), P < 0.000 01], 且安全性好[OR=3.09, 95%CI(2.31, 4.14), P < 0.000 01]。

基于现有文献, 在治疗幽门螺杆菌感染时, 复方嗜酸乳杆菌片与四联疗法或三联疗法联合用药具有一定的临床优势, 能提高幽门螺杆菌根除率, 降低不良反应发生率, 提高安全性。

     

Immune response to CagA protein is associated with improved platelet count after Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura

BACKGROUND: Improvement in platelet counts has been reported after eradication of Helicobacter pylori in patients with idiopathic thrombocytopenic purpura (ITP). We examined the levels of serum markers of gastritis and anti-CagA (cytotoxin-associated gene A) IgG antibody in patients with ITP to investigate whether these factors are associated with the platelet response after H. pylori eradication therapy. MATERIALS AND METHODS: One hundred and sixteen consecutive patients with ITP were assessed for H. pylori infection by (13)C-urea breath test and serum H. pylori antibody test. Patients with H. pylori infection received eradication therapy. Before and after eradication therapy, we evaluated serum levels of gastrin, pepsinogen (PG)-I, and PG-II and the anti-CagA IgG antibody titer. RESULTS: H. pylori infection was found in 67 (58%) of the 116 patients with ITP. Fifty-two infected patients received eradication therapy, which was successful in 44 patients (85%). Twenty-seven patients (62%) showed an increased platelet count and were identified as responders. The duration of ITP was shorter in responders than in nonresponders (p = .017). There was no difference of the levels of gastrin and PGs between responders and nonresponders. Before eradication therapy, the serum anti-CagA antibody titer did not differ significantly between responders and nonresponders. However, reduction in the anti-CagA antibody titer after eradication therapy was significantly greater in responders than in nonresponders (p = .013). CONCLUSIONS: H. pylori eradication therapy improves the platelet count in H. pylori-positive patients with ITP of short duration. Immune response of hosts to CagA protein of H. pylori may play a role in the pathogenesis of ITP.     

Helicobacter pylori-induced IL-8 production by gastric epithelial cells up-regulates CD74 expression

CD74, or the class II MHC-associated invariant chain, is best known for the regulation of Ag presentation. However, recent studies have suggested other important roles for this protein in inflammation and cancer studies. We have shown that CD74 is expressed on the surface of gastric cells, and Helicobacter pylori can use this receptor as a point of attachment to gastric epithelial cells, which lead to IL-8 production. This study investigates the ability of H. pylori to up-regulate one of its receptors in vivo and with a variety of gastric epithelial cell lines during infection with H. pylori. CD74 expression was increased dramatically on gastric biopsies from H. pylori-positive patients and gastric cell lines exposed to the bacteria. Gastric cells exposed to H. pylori-conditioned medium revealed that the host cell response was responsible for the up-regulation of CD74. IL-8 was found to up-regulate CD74 cell surface expression because blocking IL-8Rs or neutralizing IL-8 with Abs counteracted the increased expression of CD74 observed during infection with H. pylori. These studies demonstrate how H. pylori up-regulates one of its own receptors via an autocrine mechanism involving one of the products induced from host cells.     

Production of reactive oxygen species in peripheral blood is increased in individuals with Helicobacter pylori infection and decreased after its eradication

BACKGROUND: Helicobacter pylori infection has been reported to cause gastroduodenal ulcer, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Recent studies have suggested that H. pylori infection may also associate with other diseases, including hematologic and dermatologic disorders, and cardiovascular injury, by unknown mechanisms. METHODS: Production of reactive oxygen species (ROS) was determined in peripheral blood samples from 86 patients (34 H. pylori-negative and 52 H. pylori-positive subjects) using a highly sensitive chemiluminescence probe, L-012 (8-amino-5-chloro-7-phenylpyrido(3,4-d) pyridazine-1 and 4 (2H, 3H) dione). Eleven H. pylori-positive individuals were also analyzed their ROS production in peripheral blood after H. pylori eradication. RESULTS: ROS production was significantly higher in individuals with H. pylori infection than in those without infection. Enhanced production of ROS was decreased significantly after eradication of H. pylori. No correlation was found between the extent of ROS production and sex, age, smoking status, alcohol ingestion, use of medications, or serum level of C-reactive protein. CONCLUSION: These findings suggest that ROS production was enhanced in peripheral blood by H. pylori infection. Chemiluminescence analysis of blood samples using L-012 permits evaluation of systemic oxidative stress in patients with H. pylori infection.     

Genetic polymorphism of interleukin-8 (IL-8) is associated with Helicobacter pylori-induced duodenal ulcer

BACKGROUND AND AIMS: Helicobacter pylori infection almost invariably causes chronic gastritis, but only a proportion of the infected subjects develop peptic ulcers. The local inflammation associated with H. pylori infection is characterized by an increased production of the proinflammatory cytokines IL-1-B, IL-6, IL-8 and TNF-alpha. Since such cytokine production is often determined by the genetic polymorphism of regions regulating cytokine gene expression, we investigated the relationship between TNF-alpha and IL-8 polymorphisms and the development of duodenal ulcer disease. We also sought a correlation between the promoter polymorphism of the lipopolysaccharide (LPS) receptor CD14 and the formation of peptic ulcer, because CD14 plays a crucial role in the initiation of the cytokine cascade. METHODS: Genomic DNA extracted from the peripheral blood of 69 patients with H. pylori-positive duodenal ulcer disease and 47 H. pylori-positive healthy controls was analyzed for TNF-alpha -308 promoter polymorphism by RFLP, and for IL-8 -251 polymorphism by ARMS. Genetic polymorphism within the promoter of the CD14 gene was identified using the LightCycler instrument via melting point analysis. RESULTS: No significant correlation could be revealed between the TNF-alpha and CD14 promoter polymorphisms and the clinical outcome of H. pylori infection. The IL-8 A/T heterozygote mutant variant was detected with a significantly higher frequency (65.22%) among the ulcer patients than among the healthy, H. pylori-positive blood donors (36.17%), while the frequency of the normal allelic genotype (TT) was significantly higher in the control group (44.6% vs 15.9%). CONCLUSION: Analysis of the genetic predisposition to enhanced cytokine production revealed a significant association only for the IL-8 polymorphism. This observation draws attention to the possible importance of IL-8 polymorphism as a genetic predisposing factor in the pathomechanism of H. pylori-induced duodenal ulcer disease, and to the relative protection from duodenal ulcer disease that is associated with the TT genotype.     

The prevalence of peptic ulcer not related to Helicobacter pylori or non-steroidal anti-inflammatory drug use is negligible in southern Europe

BACKGROUND AND AIM: Helicobacter pylori is the major cause of peptic ulcer disease, but the proportion of H. pylori-negative peptic ulcers seems to be increasing in developed countries. We investigated the frequency of H. pylori-negative peptic ulcer without intake of nonsteroidal anti-inflammatory drugs (NSAIDs) in a Mediterranean European country. MATERIALS AND METHODS: We prospectively collected consecutive patients with an endoscopically verified active peptic ulcer over 6 months from different areas of Spain. Helicobacter pylori infection was assessed by rapid urease test and histologic examination (corpus and antral biopsies). A (13)C-urea breath test was performed if H. pylori was not detected with the invasive test. Patients were considered H. pylori-negative if all three tests were negative. NSAID use was determined by structured data collection. RESULTS: Of 754 consecutive peptic ulcer patients, 16 (2.1%) were H. pylori-negative and had not used NSAIDs before the diagnosis. Of the 472 patients who had duodenal ulcers, 95.7% (n = 452) were H. pylori-positive and only 1.69% (n = 8) were negative for both H. pylori infection and NSAID use; 193 patients had benign gastric ulcers and 87% (n = 168) of them were infected by H. pylori (p <.001 vs. duodenal ulcers). NSAID intake was more frequent in gastric ulcer patients (52.8%) than in duodenal ulcer patients (25.4%; p <.001). Consequently, the frequency of H. pylori-negative gastric ulcer in patients not using NSAID was 4.1% (n = 8). CONCLUSION: Peptic ulcer disease is still highly associated with H. pylori infection in southern Europe, and only 1.6% of all duodenal ulcers and 4.1% of all gastric ulcers were not associated with either H. pylori infection or NSAID use.     

Gastric mucosal cytokine responses in Helicobacter pylori-infected patients with gastritis and peptic ulcers. Association with inflammatory parameters and bacteria load

Helicobacter pylori is an important pathogen in gastroduodenal inflammation and ulceration. Several mechanisms have been proposed to explain its role. We studied the cytokine production patterns in situ in gastric mucosal biopsies from H. pylori-positive and H. pylori-negative patients with dyspepsia. Immunohistochemistry with monoclonal antibodies was used. The study showed enhanced expression of interleukin (IL) -8, IL-10 and interferon-gamma (IFN-gamma) in H. pylori infection and a significant association was found between these cytokines and the following parameters: bacteria load, chronic inflammation and activity. These parameters were significantly correlated with the cell markers CD19 and CD56. The study indicates a dual effect of H. pylori on the Th1 response, i.e. a stimulation of the response verified by increased IFN-gamma and a feed-back verified by an increase of the counterinflammatory IL-10, which may dampen the inflammatory and cytotoxic effect of the Th1 response. Furthermore, the study confirms the connection between increase of IL-8 and inflammatory activity in gastric mucosa in H. pylori infection.     

Epidemiological study on Helicobacter pylori infection and extragastroduodenal disorders in Polish population.

An association between Helicobacter pylori (H. pylori) infection and extragastroduodenal disorders (EGDD) is still not clear. The aim of the study was to investigate the relationship between H. pylori infection and the symptoms of coronary artery disease (CAD), facial dermatological changes (FDC), gastroesophageal reflux diseases (GERD), and periodontal diseases (PD) in Polish population. The study was performed between 1996-1999 year on 7,060 adult inhabitants of municipal area of Krakow (aged 18-76, mean 46.3 year; 55.8% female, 44.2% male): 2,204 subjects with EGDD and 4,856 without symptoms of EGDD. Each patient responded to a detailed questionnaire under supervision of medical staff. The H. pylori status was assessed non-invasively using urea breath test (UBT) with capsulated low-dose 13C-UBT (38 mg). Exclusion criteria were: recent H. pylori eradication, treatment with PPI, bismuth and/or antibiotics in the last 4 weeks. Four groups of cases with EGDD symptoms were selected. Within each group exclusively only one of studied symptoms was recorded. The study included 328, 138, 688, and 1,050 patients with CAD, FDC, GERD and PD, respectively. For each studied group an age and sex-matched asymptomatic controls were selected (897, 387, 1,083, and 2,489 control patients). Results: Overall H. pylori infection rate was 69,9% (in 71.4% of 2,204 cases and in 69.31% of 4,856 controls). In CAD group: 68% of 328 cases were H. pylori (+ve) vs. 70% H. pylori (+ve) of 897 controls. An association was not significant: OR = 0.93 (95% CI, 0.72-1.20). In 138 of FDC cases, 59% were H. pylori (+ve) vs. 71% H. pylori (+ve) in 387 controls showing the lack of positive association; OR = 0.60 (95% CI, 0.42-0.87). In GERD, 69% of 688 cases were H. pylori (+ve) vs. 73% of 1,083 H. pylori (+ve) controls and negative association was observed; OR=0.80 (95% CI, 0.65-1.00). In 1,050 of PD cases 75% were H. pylori (+ve) vs. 68% H. pylori (+ve) of 2,489 controls; positive association was significant; OR = 1.4 (95% CI, 1.16-1.68). We conclude that in the studied Polish population, no positive association exists between H. pylori positivity and CAD, FDC or GERD possibly due very high overall H. pylori infection rate. The only positive link observed between H. pylori infection and periodontal disease may reflect direct "in situ" H. pylori pathological action of H. pylori in oral cavity. It is not excluded that periodontal diseases may facilitate the H. pylori oro-gastric transmission and colonisation of the bacteria in the digestive tract.     

枳术宽中胶囊联合益生菌对老年幽门螺杆菌阳性慢性萎缩性胃炎患者的疗效

目的 探讨枳术宽中胶囊联合益生菌对老年幽门螺杆菌（H. pylori）阳性慢性萎缩性胃炎（chronic atrophic gastritis,CAG）患者的临床疗效。方法 将80例H. pylori阳性的老年慢性萎缩性胃炎患者随机分为2组,各40例。其中对照组患者给予包含雷贝拉唑、阿莫西林、克拉霉素和胶体果胶铋的标准四联疗法治疗。观察组患者将四联疗法中的胶体果胶铋替代为枳术宽中胶囊,并在此基础上加用益生菌。7天为1个疗程,全部患者治疗2个疗程。停药1个月后比较两组患者治疗前后临床症状缓解率、H. pylori根除率、不良反应发生率等情况。结果 治疗后两组患者病情均有所改善,但与对照组相比,观察组患者的症状缓解率及H. pylori根除率较高,不良反应发生率较低,差异均有统计学意义（P<0.05）。结论 枳术宽中胶囊联合益生菌可明显缓解老年CAG患者的临床症状,提高幽门螺杆菌的根除率,同时减轻患者不良反应发生率,对临床治疗CAG具有指导性意义。     

Helicobacter pylori infection is associated with reduced circulating ghrelin levels independent of body mass index

BACKGROUND: Ghrelin stimulates growth hormone and has orexigenic and adipogenic effects. Plasma ghrelin levels are reduced in obesity and possibly in Helicobacter pylori infection. AIM: To investigate whether there was a relation between H. pylori infection, body mass index (BMI) and serum ghrelin or leptin levels. METHODS: University students undergoing an annual health check-up were invited to participate. H. pylori status was based on the presence of specific IgG H. pylori antibodies in urine. Fasting serum ghrelin, leptin levels, and pepsinogen I and II levels were measured by enzyme immunoassay (EIA). RESULTS: Eight hundred and one students volunteered. There was no significant difference in the height and BMI between those with and without H. pylori infection. The population of ghrelin study consisted of 132 (66 H. pylori-positive and 66 H. pylori-negative) students matched for age, sex, and BMI. The ghrelin level in the H. pylori-positive group was significantly lower (median 55 pmol/l) compared to the H. pylori-negative group (103 pmol/l) (p < .00001). Leptin, triglyceride, total cholesterol, and HDL-cholesterol were not different between the two groups, whereas LDL-cholesterol levels were significantly higher (106 versus 100 mg/dl) (p = .03) in the H. pylori-positive group. Leptin levels correlated with the BMI (r = 0.53) (p < .00001). Among H. pylori-positive subjects, ghrelin correlated only with pepsinogen I levels (r = 0.26, p = .04). CONCLUSIONS: H. pylori infection was associated with a reduction in circulating ghrelin levels independent of sex and BMI.     

Interleukin-2 gene polymorphisms associated with increased risk of gastric atrophy from Helicobacter pylori infection

BACKGROUND: Gastric atrophy induced by Helicobacter pylori is thought to predispose patients to noncardiac gastric cancer development. However, the host genetic factors that influence the progression of gastric atrophy have not been elucidated. In this study, we examined the effects of cytokine polymorphisms on H. pylori-induced gastric atrophy. METHODS: Blood samples were taken from 454 Japanese subjects. The interleukin-2 (IL-2; T-330G), IL-4 (C-33T), and IL-13 (C-1111T) polymorphisms were genotyped by polymerase chain reaction with confronting two-pair primers (PCR-CTPP). Anti-H. pylori IgG antibody and pepsinogen I and II were measured to diagnose H. pylori infection and atrophic gastritis. RESULTS: The odds ratios (ORs) for the association between IL-2 polymorphism [OR = 2.78, 95% CI (confidence interval) = 1.26-6.17 (T/T to G/G)] or IL-4 polymorphism [OR = 2.22, 95% CI = 1.01-4.89 (T/C to C/C)] were increased significantly with gastric atrophy, whereas the corresponding OR of IL-13 polymorphism was decreased with gastric atrophy [OR = 0.61, 95% CI = 0.39-0.96 (C/T and T/T to C/C)]. There were no significant H. pylori seropositivity-related differences between these polymorphisms. We examined the relationship between these polymorphisms and gastric atrophy separately in H. pylori-seropositive and -seronegative groups. In the H. pylori-seropositive group, the IL-2 T/T (OR = 2.78, 95% CI = 1.12-6.93) had a significant association with gastric atrophy. CONCLUSIONS: These results reveal that the IL-2 gene polymorphism is associated with an increased risk of gastric atrophy induced by H. pylori infection and might predispose to gastric cancer.     

Lower prevalence of Helicobacter pylori infection with vacAs1a, cagA-positive, and babA2-positive genotype in erosive reflux esophagitis disease

BACKGROUND: Increased prevalence of esophagitis has been recognized in the West. Helicobacter pylori infection, particularly virulent strains, is proposed as a protective factor against the development of gastroesophageal reflux disease. To evaluate the relationship of reflux esophagitis with virulent H. pylori infection, we studied the prevalence of reflux esophagitis among H. pylori-infected and -uninfected patients and the genotype of isolates in Taiwan. METHODS: Patients who had routine physical examination were investigated. The severity of esophagitis was evaluated using the Los Angeles grading system. H. pylori status was assessed by histology, rapid urease test, and bacterial culture. Genotyping of vacA, cagA, and babA2 was determined by polymerase chain reaction (PCR). Risk factors for severe esophagitis were evaluated. RESULTS: Reflux esophagitis was found in 21.2% of 1622 patients. The prevalence of H. pylori infection was found in 33.0% of 276 patients with reflux esophagitis compared with 67.5% of 378 patients with normal esophagus (p < .001). Esophagitis occurred in a significantly lower rate among H. pylori-positive patients with peptic ulcer than those without peptic ulcer. cagA, babA2, and vacAs1a were detected in 100% of 143 isolates. Factors that predicted severe esophagitis included age, gender, and hiatus hernia but not H. pylori infection. CONCLUSIONS: Our study suggests significantly lower incidence of H. pylori infection with the triple-positive virulent genotype in patients with reflux esophagitis in Taiwan.     

Gastric inflammatory markers and interleukins in patients with functional dyspepsia treated with astaxanthin

The chronic active inflammation caused by Helicobacter pylori is dominated by neutrophils, macrophages, lymphocytes and plasma cells. Several interleukins are involved in the inflammatory process. The aim of this study was to investigate the effect of astaxanthin on gastric inflammation in patients with functional dyspepsia. Forty-four consecutive patients were included, and biopsies were examined for IL-4, IL-6, IL-8, IL-10, interferon-gamma, CD4, CD8, CD14, CD19, CD25 and CD30. Patients were randomized: 21 patients were treated with 40 mg of astaxanthin daily, and 23 patients were treated with a placebo. There was a significant decrease in gastric inflammation in H. pylori-positive patients from both groups. There were no significant changes in the density of H. pylori or in any of the interleukins during or after treatment. There was a significant up-regulation of CD4 and down-regulation of CD8 in patients with H. pylori treated with astaxanthin. Astaxanthin had an effect on the inflammation and on the density of H. pylori in mice in a study where the diet could be standardized without antioxidants (Bennedsen et al., 1999). These dietary conditions are impossible in studies involving humans, and may be due to the minor effect when the host have access to antioxidants in their diet.     

Organ-specific autoantibodies in children with Helicobacter pylori infection

BACKGROUND: We compared the prevalence of organ-specific autoantibodies in a group of Helicobacter pylori infected children and a group of uninfected children and investigated the relationship between the presence of relevant autoantibodies and the status of the target organs. PATIENTS AND METHODS: One hundred and twenty-four children with dyspepsia (54 boys, 70 girls; mean age 10.5 years; range 4-19) underwent gastroscopy: 56 had H. pylori infection (31 girls, 25 boys), while 68 (37 girls and 31 boys), were H. pylori-negative. All sera were tested for the presence of: parietal cell autoantibodies (PCA), intrinsic factor autoantibodies (IFA), microsomial autoantibodies, thyroglobulin autoantibodies, islet cell autoantibodies, glutamic acid decarboxylase autoantibodies, adrenal cortex autoantibodies, steroid-producing cell autoantibodies; gastrin, pepsinogen A, pepsinogen C and anti-H. pylori antibodies. The histological features and the ureA and cagA genes were also considered. RESULTS: The frequency of organ-specific autoantibodies was higher in patients with H. pylori infection than in uninfected patients (chi2-test p < .0001). Specifically gastric autoantibodies were significantly higher: seven of the 56 H. pylori-positive children were PCA-positive and one was IFA-positive (chi2-test p = .0004). The presence of autoantibodies was not associated with any clinical or biohumoral signs of disease. CONCLUSIONS: Our study detected a relationship between H. pylori infection in childhood and the presence of organ-specific autoantibodies unassociated with any clinical or biohumoral signs of disease. Helicobacter pylori infection in childhood could trigger the onset of clinical autoimmune gastritis, and/or other clinical autoimmune diseases.     

Comparison of localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma with and without Helicobacter pylori infection

BACKGROUND: The clinical features and clinical course of Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma are unclear and a treatment strategy has not yet been established. AIM: To clarify the clinical differences between H. pylori-positive and H. pylori-negative gastric MALT lymphoma, we compared these two types of gastric MALT lymphoma. MATERIALS AND METHODS: Fifty-seven patients with localized gastric MALT lymphoma were studied. H. pylori infection was present in 41 and absent in 16. Treatment consisted of antibiotic therapy and/or 30 Gy radiation therapy. Response assessment was performed every 3-6 months by esophagogastroduodenoscopy including gathering biopsy samples, endoscopic ultrasonography, clinical examination, and various imaging procedures. The median follow-up period was 37 months. RESULTS: There were no significant differences between H. pylori-positive and H. pylori-negative gastric MALT lymphoma patients in terms of sex, age, stage, gross phenotype, affected area of the stomach, or the presence of monoclonality. Complete regression was achieved with antibiotic therapy against H. pylori-negative gastric MALT lymphoma in one of nine patients (11.1%), compared to 28 of 38 patients (73.7%) with H. pylori-positive gastric MALT lymphoma (p < .001). Radiation therapy showed high effectiveness for the local control of H. pylori-negative or antibiotic-resistant gastric MALT lymphoma (92.9%), although distant recurrence was recognized in three of 14 patients (21.4%). Two of 16 patients (12.5%) with H. pylori-negative gastric MALT lymphoma died because of the transformation of the disease into diffuse large B-cell lymphoma. There was a significant difference in both the overall and cause-specific survival rate between the two groups (p = .038). CONCLUSION: Radiation therapy is the effective treatment for H. pylori-negative or antibiotic-resistant localized gastric MALT lymphoma. However, careful systemic follow-up for distant involvement should be required. Transformation into diffuse large B-cell lymphoma is thought to be the important cause of death in patients with gastric MALT lymphoma.     

Influence of polymorphisms in the NOD1/CARD4 and NOD2/CARD15 genes on the clinical outcome of Helicobacter pylori infection

Host immune response influences the clinical outcome of Helicobacter pylori infection leading to ulcer disease, gastric carcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. A genetic risk profile for gastric cancer has been identified, but genetic susceptibility to develop MALT lymphoma is still unclear. We investigated the role of NOD1 and NOD2 as intracellular recognition molecules for pathogen-associated molecules in H. pylori infection in vitro and analysed the influence of single nucleotide polymorphisms on susceptibility to ulcer disease and MALT lymphoma. Expression of NOD1 and NOD2 significantly sensitized HEK293 cells to H. pylori-induced NF-kappaB activation in a cag pathogenicity island (cagPAI)-dependent manner. In cells carrying the Crohn-associated NOD2 variant R702W the NF-kappaB response was significantly diminished. NOD1/NOD2 expression levels were induced in the gastric epithelium in H. pylori-positive patients. No mutations were found to be associated with gastritis or gastric ulcer development. However, the R702W mutation in the NOD2/CARD15 gene was significantly associated with gastric lymphoma. Carrier of the rare allele T had a more than doubled risk to develop lymphoma than controls [odds ratio (OR): 2.4, 95% confidence interval (CI): 1.2-4.6; P < 0.044]. H. pylori-induced upregulation of NOD1 and NOD2 in vivo may play a critical role in the recognition of this common pathogen. A missense mutation in the leucine-rich region of CARD15 is associated with gastric lymphoma.