2014年10月Pubmed幽门螺杆菌相关文献汇总
1. LOTUS 试验的事后分析：每日维持20mg埃索美拉唑治疗量对患者的症状和生活质量的长期影响
对参与LOTUS trial (ClinicalTrials.gov identifier: NCT00251927)的256例GRED患者进行包括胃镜、24小时试管PH监测在内的检测来评估消化道的症状。结果证明每日20mg埃索美拉唑能够为慢性GRED患者提供长期有效的治疗效果。研究结果提到无HP感染的患者有可能埃索美拉唑的每日量应该加到40mg。
Long-term effect on symptoms and quality of life of maintenance therapy with esomeprazole 20 mg daily: a post hoc analysis of the LOTUS trial.
Lundell L1, Hatlebakk J, Galmiche JP, Attwood SE, Ell C, Fiocca R, Persson T, Nagy P, Eklund S, Lind T.
Abstract
Objective:To assess the long-term effect on symptoms and quality of life of esomeprazole 20 mg once daily, a recommended dose for maintenance therapy of gastroesophageal reflux disease (GERD).
Research design and methods: This is a post hoc analysis of 5 year data from patients in the LOTUS trial (ClinicalTrials.gov identifier: NCT00251927) who were randomized to esomeprazole 20 mg once daily. All participants had chronic, symptomatic GERD responsive to treatment. Gastrointestinal symptoms were assessed by physicians and by using patient-reported outcome instruments. Investigations included gastrointestinal endoscopy (with biopsy sampling), 24 hour esophageal pH monitoring and laboratory measurements.
Results: In total, 157 of 256 patients randomized to esomeprazole 20 mg once daily remained on this dose until the end of follow-up or study discontinuation, whereas 99 patients had their dose increased because of inadequate symptom control (of these, 29 subsequently returned to the allocated dose). On logistic regression, a long objectively defined GERD history, smoking, female sex, absence of Helicobacter pylori infection and high supine baseline acid reflux into the esophagus were associated with an increased likelihood of requiring dose escalation to esomeprazole 40 mg daily (all p < 0.05). Symptoms were fairly stable and quality of life was normal throughout follow-up in patients remaining on esomeprazole 20 mg once daily, with no more than mild symptom severity, and mean (standard deviation) percentage time with intraesophageal pH <4 was reduced from 10.7 (10.7) pre-randomization to 6.3 (10.2) at 6 months and 4.9 (7.3) at 5 years. The number of serious adverse events was low (0.079 per patient per year).
Conclusions:Esomeprazole at a maintenance dose of 20 mg once daily offers effective long-term treatment for chronic GERD in patients initially responsive to the medication, with durable symptom control and sustained reductions in intraesophageal acid exposure.
2.一项长达17年的前瞻性队列研究：HP根除对消化性溃疡患者预防胃癌的影响
研究对象总数1222例。研究者分析后认为HP的根除对消化性溃疡患者胃癌发生风险降低的效果可能超过10年之久，但即便根除了Hp患者也有发生胃癌的风险。
J Gastroenterol. 2014 Oct 29.
Seventeen-year effects of eradicating Helicobacter pylori on the prevention of gastric cancer in patients with peptic ulcer; a prospective cohort study.
Take S1, Mizuno M, Ishiki K, Hamada F, Yoshida T, Yokota K, Okada H, Yamamoto K.
Abstract
BACKGROUND:
We previously reported that eradication of Helicobacter pylori in our cohort of patients with peptic ulcer disease reduced their risk of developing gastric cancer to approximately one-third after a mean follow-up period of 3.4 years (up to 8.6 years). We have now followed these patients for a longer period.
METHODS:
A total of 1,222 consecutive patients with peptic ulcer diseases who completed more than 1-year follow-up after receiving H. pylori eradication therapy were followed with annual endoscopic surveillance for a mean of 9.9 years (as long as 17.4 years).
RESULTS:
H. pylori infection was judged cured in 1,030 patients (eradication-success group) but persisted in 192 (eradication-failure group) after initial eradication therapy. In the eradication-failure group, 114 patients received re-treatment at a mean of 4.4 years after the start of follow-up, and 105 of these were cured of infection. Gastric cancer developed in 21 of the 1,030 patients in the eradication-success group and in nine of the 192 in the failure group (p = 0.04). The risk of developing gastric cancer in the eradication-success group (0.21 %/year) was significantly lower than that in the failure group (0.45 %, p = 0.049). The longest interval between the initial H. pylori eradication and the occurrence of gastric cancer was 14.5 years in the eradication-success group and 13.7 years in the eradication-failure group.
CONCLUSIONS:
A prophylactic effect for gastric cancer persists for more than 10 years after H. pylori eradication therapy, but we should be aware that cancer can develop even after that interval.
3. 枯草芽孢杆菌表面幽门螺杆菌尿素酶B的表达研究
文章提到近年来HP的耐药性越来越高。因此，研发幽门螺杆菌疫苗重新被人们所重视。研究显示，枯草芽孢杆菌表面表达的尿素酶B具有免疫原的特点，通过口服可能可以预防HP的感染。
J Med Microbiol. 2014 Oct 29. pii: jmm.0.076430-0. doi: 10.1099/jmm.0.076430-0.
Expression of Helicobacter pylori urease B on the surface of Bacillus subtilis spores.
Zhou Z1, Gong S2, Li X3, Yang Y2, Guan R2, Zhou S2, Yao S2, Xie Y2, Ou Z2, Zhao J2, Liu Z4.
Abstract
Helicobacter pylori infection is a major risk factor for chronic gastritis, digestive ulcers, gastric adenocarcinoma and lymphoma. Due to the decreasing efficacy of anti-Helicobacter pylori antibiotic therapy in clinical practice, there is renewed interest in the development of anti-Helicobacter pylori vaccines. Bacillus subtilis is nonpathogenic and can produce endospores, which can survive under extreme conditions. These features make the Bacillus subtilis spore an ideal vehicle for delivery of heterologous antigens to extreme environments such as the gastrointestinal tract. In this study, we displayed Helicobacter pylori urease B protein on the Bacillus subtilis spore coat using spore coat protein CotC as a fusion partner. Western blotting analyses were used to verify urease B surface expression on spores. Recombinant spores displaying the urease B antigen were used for oral immunization and were shown to generate humoral response in mice. Urease B-specific secretory IgA in feces and IgG in serum reached significant levels 2 weeks after oral dosing. In addition, oral immunization of recombinant urease B spores induced a significant reduction (84%) in the stomach bacterial load (0.25±0.13 x 106CFU) compared to that in non-recombinant spores treated group (1.56±0.3 x 106CFU, P < 0.01). This report shows that urease B expressed on Bacillus subtilis spores was immunogenic and oral administration of urease B spores can provide protection against Helicobacter pylori infection.
Copyright © 2014, the Society for General Microbiology.
4. 应用多能干细胞衍生的类胃组织建模研究人类相关器官的发育及其相关疾病
在应用干细胞的产生人胃组织体(hGOs)后，该研究模拟了人类器官的发育和相关疾病发病机制。研究过程中发现，幽门螺旋杆菌感染后，致病因子CagA与c-Met受体的快速结合，进而激活信号通路和诱导上皮细胞增生。
Nature. 2014 Oct 29. doi: 10.1038/nature13863. [Epub ahead of print]
Modelling human development and disease in pluripotent stem-cell-derived gastric organoids.
McCracken KW1, Catá EM1, Crawford CM1, Sinagoga KL1, Schumacher M2, Rockich BE3, Tsai YH4, Mayhew CN1,Spence JR5, Zavros Y2, Wells JM6.
Author information
Abstract
Gastric diseases, including peptic ulcer disease and gastric cancer, affect 10% of the world's population and are largely due to chronic Helicobacter pylori infection. Species differences in embryonic development and architecture of the adult stomach make animal models suboptimal for studying human stomach organogenesis and pathogenesis, and there is no experimental model of normal human gastric mucosa. Here we report the de novo generation of three-dimensional human gastric tissue in vitro through the directed differentiation of human pluripotent stem cells. We show that temporal manipulation of the FGF, WNT, BMP, retinoic acid and EGF signalling pathways and three-dimensional growth are sufficient to generate human gastric organoids (hGOs). Developing hGOs progressed through molecular and morphogenetic stages that were nearly identical to the developing antrum of the mouse stomach. Organoids formed primitive gastric gland- and pit-like domains, proliferative zones containing LGR5-expressing cells, surface and antral mucous cells, and a diversity of gastric endocrine cells. We used hGO cultures to identify novel signalling mechanisms that regulate early endoderm patterning and gastric endocrine cell differentiation upstream of the transcription factor NEUROG3. Using hGOs to model pathogenesis of human disease, we found that H. pylori infection resulted in rapid association of the virulence factor CagA with the c-Met receptor, activation of signalling and induction of epithelial proliferation. Together, these studies describe a new and robust in vitro system for elucidating the mechanisms underlying human stomach development and disease.
5. KIR基因型与幽门螺杆菌感染之间的关系
对101例研究对象的杀伤免疫球蛋白样受体（KIR）基因型和HP感染进行了分析，发现在无HP感染的患者中A单倍型相对HP阳性的患者减少。
J Clin Pathol. 2014 Oct 28. pii: jclinpath-2014-202638. doi: 10.1136/jclinpath-2014-202638. [Epub ahead of print]
KIR genotype distribution among symptomatic patients with and without Helicobacter pylori infection: is there any role for the B haplotype?
Mahfouz R1, Hoteit R1, El Hajj N1, Shammaa D1, Sharara AI2.
Abstract
Contact of peripheral blood lymphocytes with Helicobacter pylori was proved to induce non- major histocompatibility complex-restricted cytotoxicity and natural killer cells are thought to play an important role in the immunity against H. pylori.
AIMS:
In this research, we investigated any possible association between killer immunoglobulin-likereceptors (KIR) genotypes and H. pylori infection.
METHODS:
KIR genotype was analysed in 101 Lebanese symptomatic patients (51 H. pylori positive and 50 H. pylori-negative) using the KIR Genotyping SSP kit.
RESULTS:
Among the H. pylori-positive patients, the AA, AB and BB genotypical frequencies were, respectively, 43.14%, 41.18% and 15.68% with an A:B ratio of 1.76:1. The AA, AB and BB genotypes frequencies for H. pylori-negative individuals were 18%, 62% and 20%, respectively, with an A:B ratio of 0.96:1. No significant difference between patients and controls was detected.
CONCLUSIONS:
We noticed a reduced distribution of A haplotype among the 'H. pylori-negative' patients as compared with the "H. pylori-positive" group. This is the first study in the international literature that targets the correlation between KIR genotypes and H. pylori.
6. 幽门螺杆菌在日本家庭家庭内传播的分析
对从5个家庭分离出的19株Hp菌株分析结果显示，在5个家庭中母子传播占4/5；父子传播占2/5；同胞传播占4/5。
J Med Microbiol. 2014 Oct 28. pii: jmm.0.080507-0. doi: 10.1099/jmm.0.080507-0. [Epub ahead of print]
Analysis of intra-familial transmission of Helicobacter pylori in Japanese families.
Osaki T1, Konno M2, Yonezawa H3, Hojo F3, Zaman C3, Takahashi M2, Fujiwara S2, Kamiya S3.
Author information
Abstract
Intra-familial infection is considered to be one of the main routes of transmission for Helicobacter pylori in Japan. We assessed the genomic profiles of H. pylori isolates from family members by multi-locus sequence typing (MLST) and identified the original strain infecting the index child. A total of 19 isolates from 5 families were analyzed by MLST using 7 housekeeping genes and by random amplification of polymorphic DNA-polymerase chain reaction (RAPD-PCR). The phylogenetic analysis was performed using nucleotide sequences of the 7 loci. Two or more different types of H. pylori strains were indicated in 3 (K-1, K-2 and K-5) out of 5 families. Independent genotypes of H. pylori strains were detected from all members of the other two families suggesting that these strains (K26-28 and K29-33) may be dominant. Mother to child transmission of H. pylori was demonstrated in 4 out of 5 families, whilst transmission from father to child and sibling to sibling were demonstrated in 2 families and 1 family, respectively.
7. 荟萃分析：中国标准三联疗法治疗幽门螺旋杆菌感染。
49项随机对照研究共纳入了8332例患者，结论：含PPI、阿莫西林和克拉霉素的标准三联疗法不能获得理想的根除率。
World J Gastroenterol. 2014 Oct 28;20(40):14973-85. doi: 10.3748/wjg.v20.i40.14973.
Standard triple therapy for Helicobacter pylori infection in China: A meta-analysis.
Wang B, Lv ZF, Wang YH, Wang H, Liu XQ, Xie Y, Zhou XJ.
Abstract
AIM:
To assess the efficacy and safety of standard triple therapy compared with other pre-existing and new therapies in China.
METHODS:
Literature searches were conducted in the following databases: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, the VIP database, the China National Knowledge Infrastructure database, and the Chinese Biomedical Database. A meta-analysis of all randomized controlled trials (RCTs) comparing standard triple therapy for the eradication of Helicobacter pylori with pre-existing and new therapies in China was performed using Comprehensive Meta-Analysis 2.0. There were 49 studies that met our criteria and the qualities of these studies were assessed using the Jadad scale. The Mantel-Haenszel method was used for pooling dichotomous data. We also conducted subgroup analyses according to age, duration of treatment and drug type. Sensitivity analyses and a cumulative meta-analysis were also performed with CMA 2.0. Publication bias was evaluated using Egger's test, Begg's test or a funnel plot.
RESULTS:
A total of 49 RCTs including 8332 patients were assessed. This meta-analysis showed that standard triple therapy with proton pump inhibitors (PPIs), amoxicillin (AMO) and clarithromycin (CLA) was inferior to sequential therapy [relative risk (RR) = 0.863; 95% confidence interval (CI): 0.824-0.904], but was not superior to quadruple therapy (RR = 1.073; 95%CI: 0.849-1.357) or other triple therapies (RR = 1.01; 95%CI: 0.936-1.089). The meta-analysis also suggested that standard triple therapy is slightly more effective than dual therapy (RR = 1.14; 95%CI: 0.99-1.31). However, the differences were not statistically significant. We removed the only trial with a regimen lasting 14 d by sensitivity analysis and found that 7-d standard triple therapy was superior to 7-d dual therapy (RR = 1.222; 95%CI: 1.021-1.461). Moreover, a sub-analysis based on the duration of quadruple therapy indicated that the 7-d and 10-d standard triple therapies were inferior to sequential therapy (RR = 0.790; 95%CI: 0.718-0.868; RR = 0.917; 95%CI: 0.839-1.002, respectively). Additionally, there were no significant differences in cure rate or adverse events among standard triple therapy, quadruple therapy, and other triple therapies (RR = 0.940; 95%CI: 0.825-1.072; RR = 1.081; 95%CI: 0.848-1.378, respectively). Standard triple therapy had a higher occurrence of side effects than sequential therapy (RR = 1.283; 95%CI: 1.066-1.544).
CONCLUSION:
The eradication rates with a standard triple therapy consisting of PPI, AMO, and CLA are suboptimal in China, and new treatment agents need to be developed.
8. Meta分析：幽门螺杆菌感染与偏头痛的关系。
5项病例对照研究纳入了903例患者，Hp总感染率39.31%。亚组分析显示亚洲患者Hp感染率与偏头痛具有明显相关性，而欧洲患者无明显相关性。
World J Gastroenterol. 2014 Oct 28;20(40):14965-72. doi: 10.3748/wjg.v20.i40.14965.
Association between Helicobacter pylori infection and migraine: A meta-analysis.
Abstract
AIM:
To quantify the association between Helicobacter pylori (H. pylori) infection and migraine.
METHODS:
A systematic literature search of PubMed and EMBASE was conducted from inception to December 2013. Studies that provided data dealing with H. pylori infection in patients with migraine, as well as healthy controls, were selected. Meta-analysis was carried out using the odds ratio (OR) with a fixed or random effects model, and a 95%CI for the OR was calculated. An unconditional logistic regression model was used to analyze potential parameters related to H. pylori prevalence. Subgroup analyses were conducted as methods of detection and evidence grade.
RESULTS:
Five case-control studies published between 2000 and 2013 were finally identified, involving 903 patients, with a total H. pylori infection rate of 39.31%. The prevalence of H. pylori infection was significantly greater in migraineurs than in controls (44.97% vs 33.26%, OR = 1.92, 95%CI: 1.05-3.51, P = 0.001). A sensitivity test indicated that no single study dominated the combined results. Univariate regression analysis found that publication year, geographical distribution and evidence grade were relevant to the results and were the main reason for the heterogeneity. Subgroup analysis found a significantly greater infection rate of H. pyloriin Asian patients with migraine, but no statistically significant infection rate in European patients. The ORs were 3.48 (95%CI: 2.09-5.81, P = 0.000) and 1.19 (95%CI: 0.86-1.65, P = 0.288), respectively.
CONCLUSION:
The pooled data suggest a trend of more frequent H. pylori infections in patients with migraine.
9. 膜结合粘蛋白和终端粘蛋白聚糖在特发性、HP相关性、或NSAID相关性消化性溃疡中的表达
研究认为，不同酸化模式的黏蛋白可能对抵抗胃酸和胃蛋白酶的损害具有不同的保护作用。
World J Gastroenterol. 2014 Oct 28;20(40):14913-20. doi: 10.3748/wjg.v20.i40.14913.
Membrane-bound mucins and mucin terminal glycans expression in idiopathic orHelicobacter pylori, associated peptic ulcers.
Niv Y, Boltin D, Halpern M, Cohen M, Levi Z, Vilkin A, Morgenstern S, Manugian V, St Lawrence E, Gagneux P, Kaur S,Sharma P, Batra SK, Ho SB.
Author information
Abstract
AIM:
To determine the expression of membrane-bound mucins and glycan side chain sialic acids inHelicobacter pylori (H. pylori)-associated, non-steroidal inflammatory drug (NSAID)-associated and idiopathic-gastric ulcers.
METHODS:
We studied a cohort of randomly selected patients with H. pylori (group 1, n = 30), NSAID (group 2, n = 18), combined H. pylori and NSAID associated gastric ulcers (group 3, n = 24), and patients with idiopathic gastric ulcers (group 4, n = 20). Immunohistochemistry for MUC1, MUC4, MUC17, and staining for Erythrina cristagalli agglutinin and Sambucus nigra agglutinin (SNA) lectins was performed on sections from the ulcer margins.
RESULTS:
Staining intensity of MUC17 was higher in H. pylori ulcers (group 1) than in idiopathic ulcers (group 4), 11.05 ± 3.67 vs 6.93 ± 4.00 for foveola cells, and 10.29 ± 4.67 vs 8.00 ± 3.48 for gland cells, respectively (P < 0.0001). In contrast, MUC1 expression was higher in group 4 compared group 1, 9.89 ± 4.17 vs 2.93 ± 5.13 in foveola cells and 7.63 ± 4.60 vs 2.57± 4.50 for glands, respectively (P < 0.0001). SNA lectin staining was increased in group 4, in parallel to elevated MUC1 expression, indicating more abundant α2-6 sialylation in that group.
CONCLUSION:
Cytoplasmic MUC17 staining was significantly decreased in the cases with idiopathic ulcer. The opposite was observed for both MUC1 and SNA lectin. This observation may reflect important pathogenic mechanisms, since different mucins with altered sialylation patterns may differ in their protection efficiency against acid and pepsin.
10. 综述：评价不同类型、不同剂量、不同疗程质子泵抑制剂在根除HP中的作用，细菌对克拉霉素和甲硝唑的耐药性是根除失败最主要的的原因。
World J Gastroenterol. 2014 Oct 28;20(40):14527-14536.
Evidence-based assessment of proton-pump inhibitors in Helicobacter pylorieradication: A systematic review.
Author information
Abstract
Peptic ulcer disease continues to be issue especially due to its high prevalence in the developing world.Helicobacter pylori (H. pylori) infection associated duodenal ulcers should undergo eradication therapy. There are many regimens offered for H. pylori eradication which include triple, quadruple, or sequential therapy regimens. The central aim of this systematic review is to evaluate the evidence for H. pylori therapy from a meta-analytical outlook. The consequence of the dose, type of proton-pump inhibitor, and the length of the treatment will be debated. The most important risk factor for eradication failure is resistance to clarithromycin and metronidazole.