Helicobacter pylori eradication to prevent gastric cancer： underlying molecular and cellular mechanisms

Numerous cellular and molecular events have been described in development of gastric cancer. In this article, we overviewed roles of Helicobacter pylori (H pylori) infection on some of the important events in gastric car-cinogenesis and discussed whether these cellular and molecular events are reversible after cure of the infection. There are several bacterial components affecting gastric epithelial kinetics and promotion of gastric carci-nogenesis. The bacterium also increases risks of genetic instability and mutations due to NO and other reactive oxygen species. Epigenetic silencing of tumor suppressor genes such as RUNX3 may alter the frequency of phe-notype change of gastric glands to those with intestinal metaplasia. Host factors such as increased expression of growth factors, cytokines and COX-2 have been also reported in non-cancerous tissue in H py/ori-positive subjects. It is noteworthy that most of the above phenomena are reversed after the cure of the infection. However, some of them including overexpression of COX-2 continue to exist and may increase risks for carcinogenesis in metaplastic or dysplastic mucosa even after successful H pylori eradication. Thus, H pylori eradication may not completely abolish the risk for gastric carcinogenesis. Efficiency of the cure of the infection in suppressing gastric cancer depends on the timing and the target population, and warrant further investigation.     

Helicobacter pyloriinfection and respiratory diseases： a review

In the past few years, a variety of extradigestive disorders, including cardiovascular, skin, rheumatic and liver diseases, have been associated with Helicobacter pylori (H. pylori) infection. The activation of inflammatory mediators by H. pylori seems to be the pathogenetic mechanism underlying the observed associations. The present review summarizes the current literature, including our own studies, concerning the association between H. pylori infection and respiratory diseases. A small number of epidemiological and serologic, case-control studies suggest that H. pylori infection may be associated with the development of chronic bronchitis. A frequent coexistence of pulmonary tuberculosis and H. pylori infection has also been found. Moreover, recent studies have shown an increased H. pylori seroprevalence in patients with bronchiectasis and in those with lung cancer. On the other hand, bronchial asthma seems not to be related with H. pylori infection. All associations between H. pylori infection and respiratory diseases are primarily based on case-control studies, concerning relatively small numbers of patients. Moreover, there is a lack of studies focused on the pathogenetic link between respiratory diseases and H. pylori infection. Therefore, we believe that larger studies should be undertaken to confirm the observed results and to clarify the underlying pathogenetic mechanisms.     

Furazolidone therapy for Helicobacter pylori： Is it effective and safe？

Some aspects related with the use of furazolidone as a rescue therapy for Helicobacter pylori （H pylorl） infection should be remarked, especially regarding its potential oncologic risk. The inclusion of furazolidone in a treatment regimen for H pylori infection is, at least, controversial, and it does not appear to be safe.     

H pylori eradication：A randomized prospective study of triple therapy with or without ecabet sodium

AIM： To investigate whether adding ecabet sodium to the standard triple therapy for H pylori infection improve eradication rate. METHODS： Two hundred and fifty-seven H pylori-infected patients were randomly assigned to standard triple therapy （group A, n = 129） or triple therapy plus ecabet sodium （group B, n = 128）. Successful eradication was defined as a negative 13C-urea breath test 6-8 wk after completion of treatment. RESULTS： After completion of therapy, 194/257 patients showed negative 13C-urea breath test results. According to intention-to-treat analysis, the infection was eradicated in 93/129 （72.1%） patients in group A and 101/128 （78.9%） in group B （P = 0.204）. Per-protocol analysis showed successful eradication in 93/118 （78.8%） patients from group A and 101/114 （88.6%） from group B （P = 0.044）. There were no significant differences in the side effects experienced by the patients in the two treatment groups. CONCLUSION： Our results suggest that the addition of ecabet sodium improves the efficacy of the standard triple therapy for H pylori.     

Is a 7-day Helicobater pylori treatment enough for eradication and inactivation of gastric inflammatory activity？

AIM： To compare the efficacy of a 7-d vs 10-d triple therapy regarding H pylori eradication, endoscopic findings and histological gastric inflammatory inactivation in the Ecuadorian population.
METHODS： 136 patients with dyspepsia and H pylori infection were randomized in 2 groups （68 per group）： group 1, 7-d therapy; group 2, 10-d therapy. Both groups received the same medication and daily dosage： omeprazole 20 mg bid, clarithromycin 500 mg bid and amoxicillin 1 g bid. Endoscopy was performed for histological assessment and H pylori infection status before and 8 wk after treatment.
RESULTS： H pylori was eradicated in 68% of group 1 vs 83.8% of group 2 for the intention-to-treat analysis （ITT） （P = 0.03; OR = 2.48; 95% CI, 1.1-5.8）, and 68% in group 1 vs 88% in group 2 for the per-protocol analysis （PP） （P = 0.008; OR = 3.66; 95% CI, 1.4-10）. Endoscopic gastric mucosa normalization was observed in 56.9% in group 1 vs 61.2% in group 2 for ITT, with similar results for the PP, the difference being statistically not significant. The rate of inflammatory inactivation was 69% in group 1 vs 88.7% in group 2 for ITT （P = 0.007; OR = 3.00; 95% CI, 1.2-7.5）, and 69% in group 1 vs96% in group 2 for PP （P = 0.0002; OR = 7.25; 95% CI, 2-26）.
CONCLUSION： In this Ecuadorian population, the 10-d therapy was more effective than the 7-d therapy for H pylori eradication as well as for gastric mucosa inflammatory inactivation.     

Azithromycin-containing versus standard triple therapy for Helicobacterpylori eradication： A meta-analysis

AIM: To evaluate whether adding azithromycin to firstline Helicobacter pylori (H pylori ) eradication improved eradication and reduced side effects. METHODS: Eligible articles were identified by searches of electronic databases. We included all randomized trials that compared azithromycin-containing with standard triple-therapy regimens for first-line treatment of H pylori infection. Statistical analysis was performed with Review Manager 5.0.10. Sub-analyses were also performed.RESULTS: We identified 14 randomized trials (1431 patients). Pooled H pylori eradication rates were 72.01% (95% CI: 58.09%-85.93%) and 69.78% (95% CI: 66.47%-73.09%) for patients with or without azithromycin by intention-to-treat analysis, and the odds ratio (OR) was 1.17 (95% CI: 0.64-2.14). The occurrence of side effects differed significantly and was 15.81% (95% CI: 12.50%-19.12%) and 25.20% (95% CI: 21.44%-28.96%) for treatment with or without azithromycin, respectively, and the summary OR was 0.58 (95% CI: 0.41-0.82). Furthermore, the azithromycin-containing group had a lower occurrence of diarrhea, nausea and taste disturbance. CONCLUSION: Our review suggests that azithromycincontaining triple-therapy regimens could be equally effective in eradication of H pylori compared with standard first-line triple-therapy regimens.     

Gastrin and antral G cells in course of Helicobacter pylori eradication： Six months follow up study

ABM: To assess long-term effects of Helicobacter pylori (H pylori) eradication on antral G cell morphology and function in patients with and without duodenal ulcer (DU). METHODS: Consecutive dyspeptic patients referred to the endoscopy entered the study. Out of 39 H pylori positive patients, 8 had DU (Hpylori+DU) and 31 gastritis (Hpylori +G). Control groups consisted of 11 uninfected dyspeptic patients (CG1) and 7 healthy volunteers (CG2). Basal plasma gastrin (PGL), antral tissue gastrin concentrations (ATGC), immunohistochemical and electron microscopic characteristics of G cells were determined, prior to and 6 mo after therapy. RESULTS: We demonstrated elevated PGL in infected patients compared to uninfected controls prior to therapy. Elevated PGL were registered in all H pylori+patients (H pylori +DU: 106.78±22.72 pg/mL, H pylori+G: 74.95±15.63, CG1: 68.59±17.97, CG2: 39.24±5.59 pg/mL, P<0.01). Successful eradication (e) therapy in H pylori+patients lead to significant decrease in PGL (H pylori+DU:59.93±9.40 and H pylori+Ge: 42.36±10.28 pg/mL, P<0.001). ATGC at the beginning of the study were similar in infected and uninfected patients and eradication therapy lead to significant decrease in ATGC in H pylori+gastritis, but not in DU patients. In the H pylori+DU patients, the mean number of antral G cells was significantly lower in comparison with all other groups (P<0.01), but after successful eradication was close to normal values found in controls. By contrast, G cell number and volume density were significantly decreased (P<0.01) in H pylori+Ge group after successful eradication therapy (294±32 and 0.31±0.02, respectively), in comparison to values before eradication (416±40 and 0.48±0.09). No significant change of the G cell/total endocrine cell ratio was observed during the 6 mo of follow up in any of the groups. A reversible increase in G cell secretory function was seen in all infected individuals, demonstrated by a more prominent secretory apparatus. However, differences between DU and gastritis group were identified. CONCLUSION: H pylori infection induces antral G cell hyperfunction resulting in increased gastrin synthesis and secretion. After eradication therapy complete morphological and functional recovery is observed in patients with gastritis. In the DU patients some other factors unrelated to the H pylori infection influence antral G cell morphology and function.     

Helicobacter pylori infection and endocrine disorders： Is there a link？

Helicobacter pylori （H pylori） infection is a leading world-wide infectious disease as it affects more than half of the world population and causes chronic gastritis, peptic ulcer disease and gastric malignancies. The infection elicits a chronic cellular inflammatory response in the gastric mucosa. However, the effects of this local inflammation may not be confined solely to the digestive tract but may spread to involve extraintestinal tissues and/or organs. Indeed, H pylori infection has been epidemiologically linked to extra-digestive conditions and diseases. In this context, it has been speculated that Hpylori infection may be responsible for various endocrine disorders, such as autoimmune thyroid diseases, diabetes mellitus, dyslipidemia, obesity, osteoporosis and primary hyperparathyroidism. This is a review of the relationship between H pylori infection and these endocrine disorders.     

Cure of alopecia areata after eradication of Helicobacter pylori： A new association？

Alopecia areata is a disease of the hair follicles,with strong evidence supporting autoimmune etiology.Alopecia areata is frequently associated with immune-mediated diseases with skin manifestations such as psoriasis and lichen planus,or without skin manifestations such as autoimmune thyroiditis and idiopathic thrombocytopenic purpura.Helicobacter pylori(H.pylori) infection is present in around 50% of the world's population and has been associated with a variety of immune-mediated extra-digestive disorders ...     

cagA and vacA genotype of Helicobacter pylori associated with gastric diseases in Xi＇an area

AIM: To establish stock of clinical Helicobacter pylori (H.pylon) isolates, to perform cagA and vacA typing of these isolates, to evaluate the relationship between genotypes of cagA and vacA and upper gastrointestinal diseases and to assess the association of vacA genotypes with presence of the pathogenicity marker-cagA.METHODS: Clinical H.pylori strains were isolated from the antrum of 259 patients in Clumbia agar. The isolated H.pylori strains were identified by histology, and16SrRNA PCR.CagA genotypes were detected by colony hybridization, the probe was derived from the cloned plasmid PcagA, and digested by EcoRI-HindⅢ and the isolated PcagA DNA fragment was radioactively labelled by the random priming method. vacA genes types (s,m)and subtypes (s1a, s1b,s2) were typed by PCR. Vacuolating toxin was detected with neutral red absorb test. The results were treated statistically by χ2test, ttest, and rank sum test.RESULTS: A total of 192 clinical H. pylori strains were isolated and the stock of Helicobacter pylori was established. The total positive rate of cagA was 87 % in all gastric diseases,and 95 % in gastric cancer group. There was a difference between gastric cancer group and the other groups (P＜0.05)except duodenal ulcer group. The expression of type s1 of vacA was more than type s2 (P＜0.05), and, the expression of type m1 was equal to type m2. In gastric cancer group,there was a difference between s1a and s1b (P＜0.05), and s1a was more than s1b. Vacuolating toxins were more in Xi′an area isolates.CONCLUSION: The cagA+ vacA type s1 clinical isolates are more in Xi′an area, but this can not serve as an index to predict gastric cancer.     

Probiotics in Helicobacter pylori eradication therapy: A systematic review and meta-analysis

AIM: To summarize the evidence from randomized controlled trials(RCTs) regarding the effect of probiotics by using a meta-analytic approach.METHODS: In July 2013, we searched PubM ed, EMBASE, Ovid, the Cochrane Library, and three Chinese databases(Chinese Biomedical Literature Database, Chinese Medical Current Content, and Chinese Scientific Journals database) to identify relevant RCTs. We included RCTs investigating the effect of a combination of probiotics and standard therapy(probiotics group) with standard therapy alone(control group). Risk ratios(RRs) were used to measure the effect of probiotics plus standard therapy on Helicobacter pylori(H. pylori) eradication rates, adverse events, and patient compliance using a random-effect model. RESULTS: We included data on 6997 participants from 45 RCTs, the overall eradication rates of the probiotic group and the control group were 82.31% and 72.08%, respectively. We noted that the use of probiotics plus standard therapy was associated with an increased eradication rate by per-protocol set analysis(RR = 1.11; 95%CI: 1.08-1.15; P < 0.001) or intention-totreat analysis(RR = 1.13; 95%CI: 1.10-1.16; P < 0.001). Furthermore, the incidence of adverse events was 21.44% in the probiotics group and 36.27% in the control group, and it was found that the probiotics plus standard therapy significantly reduced the risk of adverse events(RR = 0.59; 95%CI: 0.48-0.71; P < 0.001), which demonstrated a favorable effect of probiotics in reducing adverse events associated with H. pylori eradication therapy. The specific reduction in adverse events ranged from 30% to 59%, and this reduction was statistically significant. Finally, probiotics plus standard therapy had little or no effect on patient compliance(RR = 0.98; 95%CI: 0.68-1.39; P = 0.889).CONCLUSION: The use of probiotics plus standard therapy was associated with an increase in the H. pylori eradication rate, and a reduction in adverse events resulting from treatment in the general population. However, this therapy did not improve patient compliance.     

Fourth-generation quinolones in the treatment of Helicobacter pylori infection: a meta-analysis

AIM To assess the efficacy and safety of fourth-generation quinolones for helicobacter pylori(h. pylori) eradication, we conducted this systematic review and metaanalysis of randomized clinical trials. METHODS Major literature databases(Pub Med, EMBASE and the Cochrane Central Register of Controlled Trials) were searched for relevant articles published prior to February 2018. We performed a meta-analysis of all randomized clinical trials that examined the efficacy of h. pylori eradication therapies and included fourthgeneration quinolones in the experimental arm. Subgroup analyses by regions and different types of fourth-generation quinolones were also performed.RESULTS Ten studies including a total of 2198 patients were assessed. A meta-analysis of randomized controlled trials showed that the eradication rate of therapies containing non-fourth-generation quinolones was significantly lower than that of therapies containing fourth-generation quinolones by intention-to-treat(ITT) analysis [75.4% vs 81.8%; odds ratio(OR) = 0.661; 95% confidence interval(CI): 0.447-0.977; P = 0.038]. This analysis also showed that the eradication rate of the therapies containing non-fourth-generation quinolones was inferior to that of therapies containing fourth-generation quinolones by perprotocol analysis(79.1% vs 84.7%; OR = 0.663; 95%CI: 0.433-1.016; P = 0.059). Moreover, the occurrence of side effects was significantly different between the control and experimental groups by ITT analysis(30.6% vs 19.5%; OR = 1.874; 95%CI: 1.120-3.137; P = 0.017). The sub-analyses also showed significant differences in moxifloxacin therapies vs other fourth-generation quinolone therapies(84.3% vs 71.9%) and in Asian vs European groups(76.7% vs 89.1%).CONCLUSION Therapies containing fourth-generation quinolones achieved a poor eradication rate in the treatment of h. pylori infection. Such regimens might be useful as a rescue treatment based on antimicrobial susceptibility testing. Different antibiotics should be chosen in different regions.     

Probiotic monotherapy and Helicobacter pylori eradication: A systematic review with pooled-data analysis

AIM To define probiotic monotherapy effect on Helicobacter pylori(H. pylori) status by performing a systematic review.METHODS Methods of analysis and inclusion criteria were based on PRISMA recommendations. Relevant publications were identified by searching Pub Med, MEDLINE, Science Direct, and EMBASE. The end-point was to estimate eradication rate and urea breath test delta value before and after probiotic monotherapy across all studies and, overall, with a pooled data analysis. Adverse events of probiotic therapy were evaluated. The data were expressed as proportions/percentages, and 95%CIs were calculated. For continuous variables, we evaluated the weighted mean difference. Odd ratios(ORs) were calculated according to the Peto method for the comparison of eradication rates between probiotics and placebo.RESULTS Eleven studies were selected. Probiotics eradicated H. pylori in 50 out of 403 cases. The mean weighted eradication rate was 14%(95%CI: 2%-25%, P =0.02). Lactobacilli eradicated the bacterium in 30 out of 235 patients, with a mean weighted rate of 16%(95%CI: 1%-31%). Saccharomyces boulardii achieved eradication in 6 out of 63 patients, with a pooled eradication rate of 12%(95%CI: 0%-29%). Multistrain combinations were effective in 14 out of 105 patients, with a pooled eradication rate of 14%(95%CI: 0%-43%). In the comparison of probiotics vs placebo, we found an OR of 7.91 in favor of probiotics(95%CI: 2.97-21.05, P 0.001). Probiotics induced a mean reduction in delta values higher than placebo(8.61% with a 95%CI: 5.88-11.34, vs 0.19% for placebo, P 0.001). Finally, no significant difference in adverse events was found between probiotics and placebo(OR = 1, 95%CI: 0.06-18.08).CONCLUSION Probiotics alone show a minimal effect on H. pylori clearance, thus suggesting a likely direct role.     

Allicin as add-on therapy for Helicobacter pylori infection: A systematic review and meta-analysis

BACKGROUND Allicin(2-propene-1-sulfinothioic acid S-2-propenyl ester, diallyl thiosulfinate)extracted from garlic, has proven activity against Helicobacter pylori(H. Pylori)infection. In recent years, clinical trials have explored its utility as an add-on therapy with variable outcomes reported.AIM To perform a systemic review of allicin as an add-on treatment for H. Pylori infection and assess its efficacy in randomized controlled trials(RCTs).METHODS Electronic databases including MEDLINE, EMBASE, the Web of Science, the Cochrane Database, the China National Knowledge Infrastructure Database,Chinese VIP Information Databases, Chinese Medical Databases, and the WanFang Database were searched for keywords including "allicin", "Helicobacter pylori", "randomized clinical trials", and their synonyms. A meta-analysis was performed using the fixed-effects model for low heterogeneity and the randomeffects model for high heterogeneity with sensitivity analysis. Bias was evaluated using Egger's tests. Trial sequential analysis(TSA) was used to evaluate information size and treatment benefits. The Grading of Recommendations Assessment, Development and Evaluation(GRADE) was used to assess the level of quality, and studies were classed as "high quality", "moderate quality", "low quality", and "very low quality".RESULTS A total of eight RCTs consisting of 867 participants(435 from the allicin group and 432 from the control group) were included. Eradication rate in the allicin group(93.33%, 406/435) was significantly higher than that of the control group(83.56%, 361/432) [I~2 = 0%, odds ratio(OR) = 2.75, 95% confidence interval(CI):1.74-4.35, P 0.001]. The healing rate of ulcers following H. pylori therapy in the allicin group(86.17%, 349/405) was significantly higher than that of the control group(75.87%, 305/402) [I~2 = 0%, OR = 2.05, 95%CI: 1.39-3.03, P 0.001]. The total remission rate of peptic ulcers across all allicin groups was 95.99%, which was significantly higher than that of controls [95.99%(359/374) vs 89.25%(332/372), I~2 = 0, heterogeneity P = 0.84, OR = 3.13, 95%CI: 1.51-6.51, P =0.002].No significant differences in side effects were observed. TSA suggested that the trials were of sufficient standard to draw reliable conclusions. The quality of outcomes including eradication rates and side effects was graded as "very low"due to downgrades for "risk of bias" and "indirectness". Other outcomes such as ulcer healing rates and total ulcer remission rates were graded as "low" due to downgrades for "risk of bias".CONCLUSION Allicin as an add-on therapy improves H. pylori eradication, healing of ulcers, and remission of symptoms. These results are suggested to be treated with caution due to limited quality.     

Hybrid,sequential and concomitant therapies for Helicobacter pylori eradication: A systematic review and meta-analysis

AIM: To compare hybrid therapy(HT) with traditional sequential therapy(ST) and concomitant therapy(CT) for Helicobacter pylori(H. pylori) eradication.METHODS: We performed an electronic search of Pub Med, Embase, and the CENTRAL database. Randomized controlled trials(RCTs) of HT were included in the meta-analysis. The primary outcome was the eradication rate of H. pylori. The secondary outcomes included the compliance rate and adverse event rate. Effect estimates were pooled using the random-effects model.RESULTS: Twelve studies were included. Pooled results showed no significant differences in eradication rate between HT and ST in per-protocol(PP) analysis(RR = 1.03, 95%CI: 0.94-1.12, P = 0.59) or in intention-totreat(ITT) analysis(RR = 1.00, 95%CI: 0.89-1.12, P = 0.94). HT and ST showed similarly high compliance rate(96% vs 98%, P = 0.55) and acceptable adverse event rate(30.3% vs 28.2%, P = 0.63). No significant results were seen in the eradication rate between HT and CT in PP analysis(RR = 1.01, 95%CI: 0.96-1.05, P = 0.76) or in ITT analysis(RR = 0.99, 95%CI: 0.95-1.03, P = 0.47). HT displayed a slightly higher compliance rate than CT(95.8% vs 93.2%, P 0.05). The adverse event rates of HT and CT were similar(39.5% vs 44.2%, P = 0.24).CONCLUSION: Compared with ST or CT, HT yields a similar eradication rate, high compliance rate, and acceptable safety profiles.     

含莫西沙星的三联疗法作为根除幽门螺杆菌一线方案的Meta分析

目的 综合分析含莫西沙星的三联方案作为根除幽门螺杆菌（Hp）一线方案的疗效.方法 检索比较含莫西沙星的三联方案和标准三联方案根除幽门螺杆菌治疗的随机对照临床试验,进行荟萃分析.结果 共有7项随机对照试验符合人选标准,共纳入899例患者.基于意向治疗分析的结果显示含莫西沙星组Hp根除率为85.7%,标准治疗组为74.7%,差异有显著性（P〈0.0001）.基于按符合方案集分析的结果显示含莫西沙星组Hp根除率为86.5%,标准治疗组为76.1%,差异有显著性（P〈0.0001）.进一步行敏感性分析显示,纳入高质量研究、中文研究、疗程7天的研究和不同疾病谱的研究时结果均未出现变化.结论 含莫西沙星的三联治疗方案有较高的Hp根除率,且优于目前的标准治疗方案,可以作为根除Hp的一线治疗方案.     

Standard triple, bismuth pectin quadruple and sequential therapies for Helicobacter pylori eradication

AIM: To compare the effectiveness of standard triple, bismuth pectin quadruple and sequential therapies for Helicobacter pylori (H. pylori ) eradication in a randomized, double-blinded, comparative clinical trial in China. METHODS: A total of 215 H. pylori -positive patients were enrolled in the study and randomly allocated into three groups: group A (n = 72) received a 10-d bismuth pectin quadruple therapy (20 mg rabeprazole bid , 1000 mg amoxicillin bid , 100 mg bismuth pectin qid , and 500 mg levofloxaci...     

幽门螺杆菌根除效果的影响因素分析

幽门螺杆菌(Helicobacter pylori,H.pylori)感染是最常见的细菌感染之一,影响着世界约50%的人口,被世界卫生组织定义为胃癌致病因子。H.pylori根除治疗可以降低消化性溃疡、胃癌等疾病的发病风险。目前H.pylori根除率呈逐渐下降的趋势。加深对其根除率影响因素的了解,可能有助于制定更为有效的根除治疗或预防感染的方案。本文结合国内外相关研究,对影响H.pylori根除率的因素作一概述。