重视根除幽门螺杆菌在消化不良处理中的应用

消化不良（dyspepsia）指上腹疼痛、烧灼感、餐后饱胀或早饱等症状,是一组很常见的症状群。在西方国家人群中消化不良的患病率为15％～25％,我国消化不良患者约占普通内科门诊的10％,占消化门诊的50％。消化不良显著影响患者生活质量,症状易复发,诊治费用逐年上升,因此对其的处理越来越受临床医师的重视。     

Eradication of H pylori for the prevention of gastric cancer

Infection with H pylori is the most important known etiological factor associated with gastric cancer. While colonization of the gastric mucosa with H pylori results in active and chronic gastritis in virtually all individuals infected, the likelihood of developing gastric cancer depends on environmental, bacterial virulence and host specific factors. The majority of all gastric cancer cases are attributable to H pylori infection and therefore theoretically preventable. There is evidence from animal models that eradication of H pylori at an early time point can prevent gastric cancer development. However, randomized clinical trials exploring the prophylactic effect of H pylori eradication on the incidence of gastric cancer in humans remain sparse and have yielded conflicting results. Better markers for the identification of patients at risk for H pylori induced gastric malignancy are needed to allow the development of a more efficient public eradication strategy. Meanwhile, screening and treatment of H pylori in first-degree relatives of gastric cancer patients as well as certain high-risk populations might be beneficial.     

质子泵抑制剂四联疗法作为幽门螺杆菌根除治疗一线方案的临床研究

背景：随着幽门螺杆菌（H．pylori）对抗生素耐药率的上升，传统一线治疗方案质子泵抑制剂（PPI）三联疗法的根除率逐渐下降。临床上需要新的一线治疗方案以提高H．pylori感染的初治成功率。目的：评价PPI四联1周疗法作为H．pylori根除治疗一线方案的疗效和安全性。方法：符合入选标准的H．pylori感染患者随机分为A1组（LCAB方案：兰索拉唑30mg＋克拉霉素250mg＋阿莫西林1．0g＋枸橼酸铋钾220mg，b．i．d．）、A2组（LCMB方案：兰索拉唑30mg＋克拉霉素250mg＋甲硝唑400mg＋枸橼酸铋钾220mg，b、i．d．）和B1组（LCA方案：兰索拉唑30mg＋克拉霉素500mg＋阿莫西林1、0g，b．i．d．）、B2组（LCM方案：兰索拉唑30mg＋克拉霉素500mg＋甲硝唑400mg，b．i．d、）。各组疗程均为1周。记录治疗期间发生的不良反应。疗程结束4周后以快速尿素酶试验、组织学或^13C-尿素呼气试验判断H．pylori根除情况。结果：共145例患者纳入研究。A组按方案（PP）分析H．pylori根除率显著高于B组（91．9％对79．2％，P〈0．05），意向治疗（ITT）根除率则与B组无显著差异（83．8％对74．0％，P〉0．05）。A1组PP和ITT根除率分别为93．8％和85．7％，A2组分别为90．0％和81．8％；B1组分别为79．4％和75．0％，B2组分别为78．9％和73．2％。A1与A2组比较，B1与B2组比较，差异均无统计学意义（P〉0．05）。各组均未见明显不良反应。结论：PPI四联1周疗法用于H．pylori感染的初治，疗效明显高于PPI三联1周疗法，是一种可供选择的一线治疗方案。     

Clinical Application of Gastric Histology to Monitor Treatment of Dual Therapy in H. pylori Eradication

This preliminary study attempted to test whetherpretreatment gastric histology of H. pylori infectionmay affect the success of dual therapy and to identifywhich parameter of gastric histology could be improved after dual therapy. One hundredforty-five dyspeptic patients with H. pylori infectionreceived a two-week course of dual therapy (Amoxicillin500 mg every 6 hr plus omeprazole 20 mg twice a day). In each patient, three pairs of gastricbiopsies, sampled from the antrum, lower body, and upperbody near the cardia, were collected before treatmentand four weeks after completion of dual therapy. The density of H. pylori (score 1-5) and parametersof the modified Sydney system were applied to test theseverity of H. pylori-related gastric histology in eachspecimen. The total bacterial load (score 1-15) was a sum of the density of H. pylorisampled from three biopsies. The overall rate of H.pylori eradication rate by dual therapy is 73.1%(106/145). Univariate analysis of parameters inpretreatment histology disclosed that the presence ofmucosal atrophy (P < 0.01), lymphoid follicles (P< 0.005), and higher-density H. pylori (P < 0.001)predisposed to dual therapy failure. Multivariateanalysis by stepwise logistic regression further confirmed that boththe density of bacteria and the presence of lymphoidfollicles are the two major factors related to theoutcome of dual therapy (P < 0.001). Four weeks after dual therapy was completed, only patients withsuccessful eradication significantly improved in thesegastric histology parameters: acute activity, chronicinflammation, eosinophil infiltration, and mucosal atrophy. However, the lymphoid follicle andintestinal metaplasia were not significantly improvedduring the study period. The eradication rates amongthree subgroups with different total bacterial loads (group I: 1-5; II: 6-10; III: 11-15) discloseda downward trend (I: 89.1%; II: 73%; III: 52.7%). It isconcluded that dual therapy could improve gastrichistology especially among patients with successful eradication of H. pylori. Evaluatingpretreatment histologic parameters, including thedensity of H. pylori and the presence of lymphoidfollicles, is valuable in predicting the success of dualtherapy.     

根除幽门螺杆菌10d序贯疗法的临床实践

在所有根除幽门螺杆菌（H．pylori）的国际指南中,标准一线治疗方案是由两种抗生素（克拉霉素加阿莫西林或甲硝唑）和一种质子泵抑制剂（PPI）组成的疗程至少7d的三联疗法。但最近一项包含超过53000例病例的荟萃分析显示,标准三联疗法的根除率低于80％。一些欧洲研究显示,H．pylori根除失败率为35％～40％。     

Eradication Therapy for Urticaria with High Titers of Anti H. pylori IgG Antibody

BackgroundIt is known that idiopathic chronic urticaria occasionally develops with Helicobacter pylori (H. pylori) infection, but the association between urticaria and H. pylori remains unknown.MethodsWe focused on the relationship between the titer of anti H. pylori IgG antibodies and urticaria. Sixty-five patients with idiopathic urticaria were divided into 3 groups by a difference of their titers. All patients in the high titer (≥ 40 U/ml) group underwent endoscopy of the upper gastrointestinal tract with antral biopsy for the Rapid Urease Test (RUT) or a culture test. We investigated the relationship between the efficacy of eradication therapy against H. pylori and urticaria.ResultsThe positive rate for H. pylori was 100% (20/20) by RUT or culture test in the high titer group. A CR using antihistamines alone was 0% (0/20) in the high titer group, 27.2% (3/11) in the low titer group and 38.2% (13/34) in the negative group respectively. A CR or PR using antihistamines was 70% (14/20) in the high titer group, 81.8% (9/11) in the low titer group and 97.1% (33/34) in the negative group. After successful eradication therapy, the CR was increased to 56% (9/16) in the high titer group.ConclusionsRegardless of acute or chronic urticaria, a high titer of anti H. pylori IgG antibody can be an indicator for undergoing upper endoscopy, and eradication therapy is strongly recommended. It will be necessary to develop diagnostic criteria for urticaria associated with H. pylori.     

Eradication therapy for Helicobacter pylori

Eradication therapy for Helicobacter pylori is recommended in a number of clinical conditions. In this article, we discuss the epidemiology and cellular mechanisms that result in antimicrobial resistance, the results of current eradication therapies, and new approaches to the management of Helicobacter pylori infection.     

Evaluation of New Therapy for Eradication of H. pylori Infection in Nude Mouse Model

Objectives: developing a new therapy for eradication of H. pylori by using the nude mouse mode). Methods: By quantifying the number of colonies of Helicobacter pylori and the score of H. pylori -associated gastritis from the gastric tissue following different drug regimens in inoculated nude mice, we evaluated the effectiveness of each regimen, including a new drug, plaunotol. Drugs were administered daily for a 1-wk period, beginning 4 wk after inoculation. Results: In the examination after therapy, the number of colonies of H. pylori and the score of gastritis in the triple-therapy group were significantly lower than in any of the singlely- and dual-drug groups or control group from 5 wk to the end of the study after inoculation. Inflammation of the stomach was less apparent in the treatment groups than in the control group. Conclusion: With the nude mouse model, we quantitatively demonstrated that the new triple therapy is the most effective therapy for eradication of H. pylori.     

Cost-Effectiveness of Treatment Regimens for the Eradication of Helicobacter pylori in Duodenal Ulcer

Background: Eradication of Helicobacter pylori with antimicrobials was recommended by a recent NIH consensus panel for all infected patients with peptic ulcer disease. The precise regimen that should be used for eradication of the infection remains uncertain because of the variety of regimens described, variable results with the regimens, and difficulties in predicting drug compliance outside clinical trials. Methods: A decision analysis tree was developed with three regimens that are widely used regimens for the eradication of H. pylori: 1 ) 2-wk triple drug therapy (metronidazole, bismuth, tetracycline with H2 receptor antagonist), 2) 2-wk omeprazole and amoxicillin, and 3) 2-wk omeprazole and clarithromycin. Traditional H2 receptor antagonist therapy was used for comparison. A 2-yr time period was chosen for study to allow sufficient time for relapse and to evaluate its effect on the treatment strategy. Probabilities for eradication, compliance, and metronidazole resistance were determined from published data, and assumptions were tested by sensitivity analysis. Results: Standard 2-wk triple drug therapy was the least expensive strategy ($720), and conventional H2 receptor antagonist therapy was the most expensive ($1791). Costs with 2-wk therapy with omeprazole and clarithromycin ($768) were lower than with omeprazole and amoxicillin ($1028). Conclusions. Treatment to eradicate H. pylori in infected patients with duodenal ulcer is a less expensive strategy than traditional therapy with H2 receptor antagonists. Triple drug therapy is the optimal regimen in areas where metronidazole resistance rates are <36% and compliance is >53%. Omeprazole and amoxicillin is not cost-effective unless eradication rates are greater than 74%. Dual drug therapy with omeprazole and clarithromycin is effective in regions where metronidazole resistance is high or where it is anticipated that there would be poor compliance with the more complicated triple drug therapy regimen.     

Treatment for Eradication of Helicobacter pylori Infection among Chronic Hepatitis C Patients

Background/Aims

Helicobacter pylori infection causes gastritis, peptic ulcers and gastric malignancies, and its eradication has been advocated by many groups. We determined the H. pylori carrier status and eradication rates of patients with chronic hepatitis C virus (HCV) infection.

Methods

In total, 76 chronically HCV-infected patients were enrolled for comparison with 228 HCV-noninfected, age- and sex-matched controls. H. pylori infection was confirmed by H. pylori antibody and urea breath testing.

Results

The H. pylori infection rate was significantly higher for HCV-infected patients (67 of 76, 88.2%) than for HCV-noninfected controls (158 of 228, 69.3%). Endoscopic findings showed that the rates of gastric ulcers and gastritis were significantly higher for the 67 HCV-infected patients with H. pylori infection (34.3% and 77.6%) than for the 158 HCV-noninfected controls with H. pylori infection (15.2% and 57.6%). Treatment to eradicate H. pylori had a significantly higher success rate for HCV-infected patients (61 of 67, 91.0%) than for HCV-noninfected controls (115 of 158, 72.8%).

Conclusions

The markedly high H. pylori eradication rate observed in this study shows that eradication of H. pylori holds promise for the improvement of the long-term health condition of patients with chronic HCV infection.     

Eradication of Helicobacter pylori with clarithromycin and omeprazole.

Clarithromycin, a new and well tolerated, acid stable macrolide antibiotic, has a similar antimicrobial spectrum to erythromycin but a better in vitro MIC90 (0.03 microgram/l-1) against Helicobacter pylori (H pylori). This study aimed at determining the eradication rate using clarithromycin 500 mg thrice daily and omeprazole 40 mg daily for two weeks. Patients were given an endoscopy and H pylori status assessed by antral culture (microaerobic conditions, for up to 10 days), antral and corpus histology tests (haematoxylin and eosin/Gimenez stains), and 13C-urea breath test (13C-UBT, European standard protocol, positive result = excess delta 13CO2 excretion > 5 per mil). Compliance was assessed by returned tablet counts. H pylori clearance at the end of treatment and eradication four weeks after finishing treatment were assessed by the 13C-UBT. Seventy three patients (54 men, median age 45 years) with duodenal ulcers (n = 42) or duodenitis/non-ulcer dyspepsia (n = 31) all with a positive 13C-UBT (mean (SEM) excess delta-13CO2 excretion = 26.6 (4.9) per mil) and either positive antral histology (n = 72) or positive antral culture (n = 35) were studied. Before treatment 2/27 (7%) isolates of H pylori were resistant to clarithromycin and five isolates were resistant to metronidazole. In 70/73 (96%) the 13C-UBT was negative immediately after finishing treatment. Four weeks later the 13C-UBT was negative in 57/73 (mean (SEM) excess delta 13CO2 excretion = 1.2 (0.3) per mil, eradication rate = 78%). Forty eight (66%) patients experienced a metallic taste while taking the tablets. Although four (5%) patients, however, could not complete the course of treatment, in only one of these four was H pylori not eradicated. These results show that duel therapy with clarithromycin and omeprazole is well tolerated. With an eradication rate of 78% it is an effective treatment for metronidazole resistant H pylori and may be an alternative to standard triple therapy.