中西药联合在根除幽门螺杆菌治疗中的作用

幽门螺杆菌(Helicobacter pylori,H.pylori)感染是很多消化系统疾病的主要病因之一,因此根除H.pylori就显得至关重要。从1999年至今,我国共颁布了5次H.pylori感染共识,根除H.pylori方案经过不断改进,从最初的PPI/RBC+2种抗生素的标准三联方案到目前第五次H.pylori感染共识推出的含铋剂四联方案,我国学者在根除H.pylori方面做了很大的努力。但目前的含铋剂四联方案仍有不足之处,抗生素的耐药问题严重影响了H.pylori的根除率,加之再感染率有上升趋势,故H.pylori的根除治疗还面临着许多困惑。所以人们开始将目光集中到了联合中药治疗上面。已有研究证实,某些中药不仅在体外有抑菌作用,而且与PPI、抗生素联合应用能明显提高H.pylori的根除率,减少药物不良反应,并减少抗生素耐药的发生。本文将近年来中西药联合根除H.pylori的相关文献作一综述,为临床用药提供参考。     

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(P0.05)。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。     

益生菌提高幽门螺杆菌根除率的随机对照双盲试验

目的了解益生菌制剂(双歧三联杆菌活检胶囊)增加标准四联根除幽门螺旋杆菌(H.pylori)方案的临床疗效及其对根除H.pylori过程的不良反应的改善情况。方法对H.pylori阳性患者采用随机双盲试验,随机分为益生菌组:埃索美拉唑钠肠溶片20mg+果胶铋200mg(2次/d,餐前0.5h)+阿莫西林1 000mg+克拉霉素500mg(2次/d,餐后即服)+益生菌(培菲康,双歧三联杆菌活菌胶囊)420mg(3次/d,与抗生素间隔2h以上);150例患者纳入安慰剂组:标准四联(同上)+安慰剂,各方案疗程均为14d,治疗结束并所用药物停药后4周对患者进行13 C呼气试验(13 C-UBT)检查,了解H.pylori根除率,治疗期间第7、14、30天对患者进行随访观察了解不良反应情况。结果 ITT分析益生菌组H.pylori根除率为85.6%,安慰剂组为75.1%;PP分析益生菌组H.pylori根除率为87.4%,安慰剂组为76.7%;益生菌组较安慰剂组不良反应发生率下降。结论联合应用益生菌制剂可提高H.pylori根除率且对治疗过程中不良反应有明显改善作用。     

益生菌在根除幽门螺杆菌中的应用

随着幽门螺杆菌耐药率的上升,幽门螺杆菌根除率逐渐下降,如何提高根除率是目前临床治疗上遇到的重要问题。益生菌不但能提高幽门螺杆菌根除率,还能降低根除幽门螺杆菌治疗的不良反应,益生菌在根除幽门螺杆菌中的应用越来越引起重视。     

益生菌抑制幽门螺杆菌的作用机制及研究进展

幽门螺杆菌在胃部疾病的发病过程中起着重要作用,是导致胃炎、胃溃疡,甚至胃癌的关键因素之一。随着胃部疾病患者幽门螺杆菌阳性检出率的不断升高,人们对于胃病和幽门螺杆菌的相关性研究也有了一定进展。如今,对于幽门螺杆菌阳性患者根除治疗的必要性,以及抗生素治疗耐药性等问题已引起广泛关注。在这种情况下,益生菌作为相对安全的天然微生物,在抑制幽门螺杆菌并促进胃部健康的益生功能方面具有重要的研究潜力。本综述对幽门螺杆菌的致病机理、不同基因分型的致病程度等方面进行了总结,并对益生菌抑制幽门螺杆菌的机制进行了探讨。建议在治疗幽门螺杆菌感染时,应与常规的治疗手段结合应用,不仅会增加幽门螺杆菌的根除率,还能减少治疗相关的副作用。     

二联方案在幽门螺杆菌根除治疗中的应用进展

幽门螺杆菌(Helicobacter pylori,H.pylori)在世界范围内感染率高,随着H.pylori对常用抗生素的耐药率逐渐增加,高效的经验性治疗方案亟待探索。新近Maastricht V/Florence共识及我国第五次幽门螺杆菌感染处理共识均推荐含铋剂四联方案可作为一线治疗方案。但是,四联方案存在用药多、药物不良反应多、患者依从性差、部分老年人及肝、肾功能不全的患者无法耐受等缺点。近年来多项研究显示高剂量阿莫西林联合质子泵抑制剂(proton pump inhibitor,PPI)的二联方案与含铋剂四联方案的疗效相近,但用药少,不良反应少,患者依从性更高,有可能成为经验性的一线治疗方案,或成为一线、二线治疗失败后的补救方案。本文就二联方案在H.pylori根除治疗中的应用进展作一综述。     

幽门螺杆菌感染的治疗进展

幽门螺杆菌(helicobacter pylori,H.pylori,HP)感染是一个世界性问题。人类感染Hp可导致慢性胃炎、胃和十二指肠溃疡、消化性胃黏膜相关的淋巴样组织淋巴瘤和胃腺癌。根除幽门螺杆菌对胃肠疾病的转归和预防有着重要作用。但是由于抗茵药物的滥用,使得对幽门螺杆茵的治疗变得棘手。本文就Hp的致病机制、耐药性问题及治疗方法等的研究进展作一综述。     

幽门螺杆菌感染的微生态治疗

幽门螺杆菌 (H elicobacter pylori,H.pylori)是慢性胃炎、消化性溃疡的主要致病因素 ,也是胃癌的主要诱发因子 ,世界卫生组织已将其列为 类致癌物质 [1 ] 。有效地治疗和根除 H.pylori感染已成为人们关注的焦点。治疗 H.pylori的方案很多 ,目前多采用抗生素多联疗法 ,但细菌抗药性的出现导致 H.pylori根除率降低 ,并可能造成菌失调、霉菌感染 ,甚至发生肝功能异常性改变。 Adamasson等 [2 ] 报道了几例使用抗生素治疗 H.pylori导致的菌群失调 :口腔内出现抗药性链球菌和葡萄球菌 ;胃粘膜中细菌数增加 ,且出现抗药性共生菌 ;肠道内微生…     

耐药幽门螺杆菌的治疗新策略

幽门螺杆菌是一种常见的胃肠道细菌,与慢性胃炎、消化性溃疡、胃黏膜相关淋巴组织淋巴瘤和胃癌的发生密切相关。既然WHO已经将幽门螺杆菌归类为I类致癌物,那么根除幽门螺杆菌就显得尤为重要。然而,由于抗生素耐药、抗生素在胃低pH环境中活性降低以及在胃内停留时间不足,幽门螺杆菌的根除率正在逐年降低。本文通过回顾幽门螺杆菌的多重耐药情况,总结了有效的非抗生素抑制或者清除幽门螺杆菌的方法和策略,如益生菌、抗菌肽、纳米技术及中药等,并探讨相关的杀菌抑菌机制,为提高幽门螺杆菌的根除率及减少胃癌发生风险提供了新的理论依据和治疗策略。     

凝结芽孢杆菌活菌片联合三联方根除幽门螺杆菌的临床研究

目的 观察和评价凝结芽孢杆菌活菌片(商品名:爽舒宝)联合三联方根除幽门螺杆菌(Helicobacter pyori,H.pylori)的疗效.方法 将90例Hpylori感染患者随机分为治疗Ⅰ组、治疗Ⅱ组和对照组,每组30例.治疗I组:常规三联方根除治疗1周的同时,口服凝结芽孢杆菌活菌片(商品名:爽舒宝),根除治疗结束后,继续服用爽舒宝1周.治疗Ⅱ组:常规根除治疗1周的同时,口服爽舒宝,根除治疗结束,继续服用爽舒宝3周.对照组:常规根除治疗1周,不用任何微生态制剂.观察记录三联方根除治疗期间和治疗结束后4周内发生的任何不良反应.结果 治疗Ⅰ组和Ⅱ组H.pylori检测值均显著低于对照组,H.pylori根除率高于对照组,差异有统计学意义(P＜0.05).治疗Ⅱ组H.pylori检测值低于治疗Ⅰ组,H.pylori根除率高于治疗Ⅰ组,差异有统计学意义(P＜0.05).三联方根除治疗中,治疗Ⅱ组和治疗Ⅰ组不良反应发生率低于对照组,差异有统计学意义(P＜0.05),治疗Ⅱ组和治疗Ⅰ组差异无统计学意义(P＞0.05).三联方根除治疗结束后4周内,治疗Ⅱ组不良反应发生率最低,其次是治疗Ⅰ组,对照组不良反应发生率最高,三组之间差异均有统计学意义(P＜0.05).结论 爽舒宝联合三联方根除H.pylori,能够提高H.pylori根除率,减少治疗过程中不良反应的发生.根除治疗结束后再服用3周的益生菌,能彻底恢复肠道菌群平衡,减少三联方根除治疗结束后不良反应的发生,值得临床推广.     

微生态制剂联合标准三联疗法根除幽门螺杆菌感染Meta分析

目的系统评价微生态制剂联合标准三联疗法能否提高H.pylori根除率,减少根除过程中的不良反应。方法从常用电子数据库检索标准三联疗法联合与未联合微生态制剂根除H.pylori的随机对照临床试验,Meta分析各项研究的根除率和不良反应发生率的合并OR值,以漏斗图检测发表偏倚。结果共15项随机临床试验符合纳入标准。三联疗法联合与未联合微生态制剂,根除率分别为79.7%（95%CI：77.1%～82.3%）和69.5%（95%CI：66.5%～72.5%）,合并OR值为1.75（95%CI：1.40～2.18）,总不良反应发生率分别为27.7%（95%CI：24.5%～30.9%）和53.0%（95%CI：49.4%～56.6%）,合并OR值为0.35（95%CI：0.21～0.60）。结论微生态制剂联合标准三联疗法可显著提高H.pylori根除率,降低根除过程中的不良反应发生率。     

Eradication of Helicobacter pylori infection favourably affects altered gastric mucosal MMP-9 levels

BACKGROUND: Helicobacter pylori gastritis is recognized as an important pathogenetic factor in peptic ulcer disease and gastric carcinogenesis, and is accompanied by strongly enhanced gastric mucosal matrix metalloproteinase-9 (MMP-9) levels. AIM: This study was performed to investigate whether H. pylori-affected gastric mucosal MMP-2 and MMP-9 levels are reversible by successful treatment of the infection. PATIENTS AND METHODS: Fifty-eight patients with H. pylori-associated gastritis were treated with a combination regimen of acid inhibitory therapy and antibiotics for 14 days. The levels and isoforms of MMP-2 and MMP-9 were measured by semiquantitative gelatin-zymography, bioactivity assay and enzyme-linked immunosorbent assay in gastric mucosal biopsy homogenates. RESULTS: Latent, active, and total MMP-9 levels decreased consistently and significantly by successful H. pylori eradication, in antrum as well as corpus mucosa, compared with those prior to treatment, irrespective of the therapy regimen used. The elevated levels remained unchanged, however, when treatment failed. MMP-2 levels did not show major alterations after H. pylori therapy. CONCLUSION: Elevated MMP-9 levels in H. pylori-infected gastric mucosa are reversible by eradication of the infection. No major changes in mucosal MMP-2 levels were observed by H. pylori eradication.     

Effect of Helicobacter pylori Eradication on Incidence of Gastric Cancer in Human and Animal Models: Underlying Biochemical and Molecular Events

Background:  Gastric cancer remains one of the most common cancers worldwide. A strong association exists between Helicobacter pylori infection and the risk of developing noncardia gastric cancer. H. pylori eradication by antibiotic treatment is regarded as a primary chemoprevention strategy to reduce gastric cancer incidence.
Aim:  To analyze the efficacy of H. pylori eradication in preventing gastric cancer in human and animal models, and to discuss whether biochemical, genetic, and epigenetic changes associated with H. pylori infection are reversible after curing the infection.
Results:  Several intervention trials have indicated that in some patients, H. pylori eradication leads to regression and prevents the progression of precancerous lesions. The eradication therapy reduces gastric cancer incidence in patients without any precancerous lesions at the baseline and is most effective before the development of atrophic gastritis. A few recent intervention studies in Japan have demonstrated significant prophylactic effects of eradication therapy on the development of gastric cancer, suggesting the use of eradication therapy in high-risk populations as a gastric cancer reduction strategy. However, gastric cancer may still develop despite successful eradication therapy. Studies in animal models have confirmed the use of eradication therapy at an early point of infection to prevent gastric cancer development.
Conclusion:  H. pylori eradication may not completely abolish the risk of gastric cancer. However, eradication therapy may be used in high-risk populations to reduce gastric cancer incidence. It can reverse many biochemical, genetic, and epigenetic changes that H. pylori infection induces in the stomach.     

国内益生菌制剂清除幽门螺杆菌感染临床疗效的Meta分析

目的对益生菌制剂清除幽门螺杆菌（H.pylori）感染的临床疗效及其对治疗中抗生素相关的不良反应的改善情况进行系统评价。方法通过计算机检索CBMdisc、CNKI、VIP以及MEDLINE等数据库,全面收集中国地区应用益生菌制剂治疗且pylori感染的随机或半随机对照试验,并按Cochrane协作网推荐的方法对其进行Meta分析。并评价Meta分析结果的稳定性和发表偏倚。结果纳入15个试验包括1572例病人,对尼py／or／清除率和不良反应改善情况分别进行Meta分析显示,试验组Hpylori清除率（88．53％）明显高于对照组（82．73％）（合并OR为1．56,95％CI为1．17—2．08,总体效应检验,Z=2．99,P=0．003）;不良反应发生率分别为5．O％和24．3％,合并OR为0．16,95％cI为0．09—0．31,表明能显著改善治疗中的不良反应发生情况,且差异具有显著性。结论联合应用益生菌制剂可以提高抗皿pylori感染治疗中的清除率,单独应用益生菌制剂清除且pylori感染也有一定的疗效。同时,益生菌制剂对且pylori感染治疗中的不良反应有较显著的改善。益生菌制剂有可能对Hpylori感染及相关疾病的防治具有重要意义。     

Efficacy of Clostridium butyricum preparation concomitantly with Helicobacter pylori eradication therapy in relation to changes in the intestinal microbiota

Antibiotic associated diarrhea due to human intestinal microbiota abnormalities is a side effect of H. pylori eradication therapy. We examined intestinal microbiota changes during H. pylori eradication therapy and the preventive effect of CBM588 as a probiotic agent. Nineteen patients with gastro-duodenal ulcer were randomly divided into three groups: group A (without probiotics), group B (with regular doses of CBM588) and group C (with double doses of CBM588). The incidence of diarrhea and soft stools during H. pylori eradication therapy was 43% in group A and 14% in group B, while none of the patients in group C reported diarrhea or soft stools. Both bacterial counts and detection rates of bifidobacteria and/or obligate anaerobe were decreased by eradication therapy. However, bacterial counts of obligate anaerobes in group C were significantly higher than in group A ( P  < 0.05). Additionally, during eradication therapy C. difficile toxin A was detected in both group A and group B but not in group C.
In conclusion, these results indicate that H. pylori eradication therapy induces antibiotic associated diarrhea due to abnormalities in intestinal microbiota and/or C. difficile . However, these side effects might be prevented by probiotics.     

Role of Probiotics in Pediatric Patients with Helicobacter pylori Infection: A Comprehensive Review of the Literature

Background: The current guidelines suggest the use of triple therapy as first choice treatment of Helicobacter pylori infection, although the eradication failure rate is more than 30%. Current interest in probiotics as therapeutic agents against H. pylori is stimulated not only by the clinical data showing efficacy of some probiotics in different gastrointestinal diseases but also by the increasing resistance of pathogenic bacteria to antibiotics, thus the interest for alternative therapies is a real actual topic. Aim: To review in vitro and in vivo studies on the role of probiotics in H. pylori infection focusing on the paediatric literature. Materials and methods: Pre‐clinical and clinical paediatric studies in English assessing the role of probiotics in H. pylori infection identified by MEDLINE search (1950–2009) were reviewed. Results: In vitro studies demonstrated an inhibitory activity of probiotics on H. pylori growth and that this effect is extremely strain specific. Available data in children indicate that probiotics seems to be efficacious for the prevention of antibiotic associated side‐effects, and might be of help for the prevention of H. pylori complications by decreasing H. pylori density and gastritis, and for the prevention of H. pylori colonization or re‐infection by inhibiting adhesion to gastric epithelial cells. There is no clear evidence that probiotics may increase the H. pylori eradication rate. Conclusion: Both in vitro and in vivo studies provide evidence that probiotics may represent a novel approach to the management of H. pylori infection.     

Indications for treatment of Helicobacter pylori infection: a systematic overview.

OBJECTIVE: To determine (a) the advantages and disadvantages of treatment options for the eradication of Helicobacter pylori and (b) whether eradication of H. pylori is indicated in patients with duodenal ulcer, nonucler dyspepsia and gastric cancer. DATA SOURCES: A MEDLINE search for articles published in English between January 1983 and December 1992 with the use of MeSH terms Helicobacter pylori (called Campylobacter pylori before 1990) and duodenal ulcer, gastric cancer, dyspepsia and clinical trial. Six journals and Current Contents were searched manually for pertinent articles published in that time frame. STUDY SELECTION: For duodenal ulcer the search was limited to studies involving adults, studies of H. pylori eradication and randomized clinical trials comparing anti-H. pylori therapy with conventional ulcer treatment. For nonulcer dyspepsia with H. pylori infection the search was limited to placebo-controlled randomized clinical trials. DATA EXTRACTION: The quality of each study was rated independently on a four-point scale by each author. For the studies of duodenal ulcer the outcome measures assessed were acute ulcer healing and time required for healing, H. pylori eradication and ulcer relapse. For the studies of nonulcer dyspepsia with H. pylori infection the authors assessed H. pylori eradication, the symptoms used as outcome measures and whether validated outcome measures had been used. DATA SYNTHESIS: Eight trials involving duodenal ulcer met our inclusion criteria: five were considered high quality, two were of reasonable quality, and one was weak. Six trials involving nonulcer dyspepsia met the criteria, but all were rated as weak. Among treatment options triple therapy with a bismuth compound, metronidazole and either amoxicillin or tetracycline achieved the highest eradication rates (73% to 94%). Results concerning treatment indications for duodenal ulcer were consistent among all of the studies: when anti-H. pylori therapy was added to conventional ulcer treatment acute ulcers healed more rapidly. Ulcer relapse rates were dramatically reduced after H. pylori eradication. All of the studies involving nonulcer dyspepsia assessed clearance rather than eradication of H. pylori. No study used validated outcome measures. A consistent decrease in symptom severity was no more prevalent in patients in whom the organism had been cleared than in those taking a placebo. Of the studies concerning gastric cancer none investigated the effect of eradication of H. pylori on subsequent risk of gastric cancer. CONCLUSIONS: There is sufficient evidence to support the use of anti-H. pylori therapy in patients with duodenal ulcers who have H. pylori infection, triple therapy achieving the best results. There is no current evidence to support such therapy for nonulcer dyspepsia in patients with H. pylori infection. Much more attention must be paid to the design of nonulcer dyspepsia studies. Also, studies are needed to determine whether H. pylori eradication in patients with gastritis will prevent gastric cancer.     

Docosahexaenoic acid inhibits Helicobacter pylori growth in vitro and mice gastric mucosa colonization

H. pylori drug-resistant strains and non-compliance to therapy are the major causes of H. pylori eradication failure. For some bacterial species it has been demonstrated that fatty acids have a growth inhibitory effect. Our main aim was to assess the ability of docosahexaenoic acid (DHA) to inhibit H. pylori growth both in vitro and in a mouse model. The effectiveness of standard therapy (ST) in combination with DHA on H. pylori eradication and recurrence prevention success was also investigated. The effects of DHA on H. pylori growth were analyzed in an in vitro dose-response study and n in vivo model. We analized the ability of H. pylori to colonize mice gastric mucosa following DHA, ST or a combination of both treatments. Our data demonstrate that DHA decreases H. pylori growth in vitro in a dose-dependent manner. Furthermore, DHA inhibits H. pylori gastric colonization in vivo as well as decreases mouse gastric mucosa inflammation. Addition of DHA to ST was also associated with lower H. pylori infection recurrence in the mouse model. In conclusion, DHA is an inhibitor of H. pylori growth and its ability to colonize mouse stomach. DHA treatment is also associated with a lower recurrence of H. pylori infection in combination with ST. These observations pave the way to consider DHA as an adjunct agent in H. pylori eradication treatment.     

Strategy for eliminating gastric cancer in Japan

A study conducted by the Japan Gast Study Group showed that eradication of Helicobacter pylori reduced the risk of gastric cancer by about one-third. However, it did not completely prevent the onset of latent gastric cancer among those at high risk (i.e., with atrophic gastritis). To prevent deaths from gastric cancer, it is necessary to eradicate H. pylori infection. We propose a program of risk stratification based on the presence of H. pylori infection with or without atrophic gastritis followed by targeted interventions. Those at no risk for gastric cancer (no H. pylori, no atrophic gastritis) need no therapy or follow-up. Those at low risk (H. pylori infected, nonatrophic gastritis) need only H. pylori eradication therapy. The smaller groups at high or very high risk need eradication and cancer surveillance. We estimated the costs and the benefits of this strategy. Gastric cancer screening by simultaneous measurement of serum pepsinogen and H. pylori antibody combined with eradication of H. pylori in all individuals at risk would initially increase national healthcare expenditure, but this would be offset by markedly reducing the cost of treating gastric cancer. The proposed strategy should prevent about 150,000 deaths from gastric cancer during the 5 years after its adoption. If the loss caused by these deaths is also taken into account, the economic effect of this strategy becomes enormous. It would probably reduce the incidence of gastric cancer by more than 80-90% within 10 years. The Japanese government should take the initiative to implement this strategy as soon as possible.