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。     

益生菌在幽门螺杆菌根除治疗中的应用

幽门螺杆菌(Helicobacter pylori,H.pylori)是导致活动性胃炎、消化性溃疡、胃癌、胃黏膜相关淋巴组织淋巴瘤等消化系统疾病的重要病因之一,已被世界卫生组织确认为Ⅰ类致癌因子,根除H.pylori对防治上述疾病有重要意义。目前临床上主要采用含抗生素的三联或四联药物进行H.pylori的根除,虽然取得一定的疗效,但随着抗生素耐药率逐年增加,根除率持续下降,限制了其广泛应用。此外,初次或多次治疗失败后再治疗可选择的药物很少。近年来人们开始尝试将益生菌应用在H.pylori根除治疗中,并取得一定疗效。本文就益生菌在辅助根除幽门螺杆菌方面的研究进展作一简单综述。     

Helicobacter pylori infection: sequential therapy followed by levofloxacin-containing triple therapy provides a good cumulative eradication rate

Background: In the eradication of H. pylori infection, even today, the main international guidelines recommend the triple therapy as first‐line regimen, although its effectiveness is clearly decreasing. As second‐line treatment, the bismuth‐containing quadruple therapy is the most used regimen, although several other therapies are studied. The Italian guidelines recommend, alternatively, sequential therapy or triple therapy as first‐line treatment and levofloxacin‐containing triple therapy as second‐line regimen. We wanted to assess the overall eradication rate of Helicobacter pylori infection in two therapeutic rounds following the Italian guidelines in clinical practice. Materials and Methods: We treated 231 consecutive Helicobacter pylori‐positive patients by sequential therapy and we verified the eradication 8–10 weeks after treatment by stool antigen test. Patients positive for stool antigen test received levofloxacin‐containing triple therapy, as second‐line therapy, according to Italian Guidelines and they were again submitted to the fecal test 8–10 weeks after the end of treatment. Results: In the first‐line regimen, we obtained an eradication rate of 92.6%, in the second‐line of 75.0% and as cumulative result we achieved a 97.8% of eradication, in per‐protocol analysis. Conclusions: Sequential therapy as first‐line and levofloxacin‐containing triple therapy as second‐line represent a good combination to eradicate Helicobacter pylori infection in only two rounds.     

The effects of probiotics on PPI-triple therapy for Helicobacter pylori eradication

Background: This study was performed to evaluate whether the addition of probiotics to proton pump inhibitor (PPI)‐based triple therapy increases the likelihood of successful Helicobacter pylori eradication. Materials and Methods: Three hundred and forty‐seven H. pylori‐infected patients were randomized into a triple‐plus‐yogurt group (yogurt group, n = 168) or a triple‐only group (control group, n = 179). Triple therapy consisted of PPI b.i.d., clarithromycin 500 mg b.i.d., and amoxicillin 1 g b.i.d. for 7 days. Yogurt group received triple therapy for 1 week and one bottle of Will yogurt per day for at 3 weeks, starting on the first day of triple therapy. Will yogurt (a Korean brand) contains Lactobacillus acidophilus HY2177, Lactobacillus casei HY2743, Bifidobacterium longum HY8001, and Streptococcus thermophilus B‐1. ¹³C‐urea breath test was performed at least 4 weeks after completion of triple therapy. Eradication rates, compliances, and adverse events were compared. Results: By intention‐to treat analysis the H. pylori eradication rates in the yogurt group 79.2% (133 of 168) was similar to that in the control group 72.1% (129 of 179) (p = .124). However, by per‐protocol (PP) analysis, the eradication rate in the yogurt group, 87.5% (133 of 152) was higher than that in the control group, 78.7% (129 of 164) (p = .037). Common adverse events were metallic taste (11.8%) and diarrhea (8.6%). The frequency of adverse effects in the yogurt group 41.1% (69/168) were higher than in the control group, 26.3% (47 of 179) (p = .003). However, most adverse events were mild to moderate in intensity, and the severities of adverse effects were similar in both groups (p = .401). Conclusions: The addition of Will yogurt to triple therapy did not reduce the side‐effects of triple therapy. But it increased the H. pylori eradication rate by PP analysis, encouraging more research in this field.     

益生菌四联疗法对比铋剂四联疗法根除幽门螺杆菌感染的Meta分析

目的 系统评价益生菌四联疗法对比铋剂四联疗法根除幽门螺杆菌（H. pylori）感染的疗效和不良反应。方法 计算机检索中英文数据库,收集上述2种方案根除H. pylori感染的随机对照试验（RCT）,检索时间均从建库至2016年10月。由2名评价员独立筛选文献、提取资料、评价纳入研究的偏倚风险,采取RevMan 5.3软件进行Meta分析。结果 最终纳入12个RCT（共1 687例患者）。Meta分析结果显示：益生菌四联组患者对比铋剂四联组的H. pylori根除率按ITT分析为：80.6% vs 81.2%;按PP分析为：81.2% vs 83.7%,差异无统计学意义（ITT分析：RR=0.99,95%CI：0.95~1.04,P=0.76;PP分析：RR=0.97,95%CI：0.93~1.01,P=0.17）;益生菌四联组的总不良反应的发生率明显低于对照组（16.0% vs 34.9%）,且差异有统计学意义（RR=0.46,95%CI：0.37~0.57,P＜0.01）。结论 现有证据显示,益生菌四联疗法与铋剂四联疗法的H. pylori根除率相当,但益生菌四联疗法的不良反应低于铋剂四联疗法。由于纳入研究数量有限,质量不高,上述结论有待高质量的研究予以验证。     

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。     

幽门螺杆菌根除疗法对肠道微生态的影响

幽门螺杆菌(Helicobacter pylori)感染是世界范围关注的焦点,进行幽门螺杆菌根除治疗是世界各国针对感染所采取的一项重要举措。但随着幽门螺杆菌耐药率,尤其是对大环内酯类药物耐药率的增加,标准三联疗法根除效果逐渐不能满足需求,更多的疗法得以推出。但是新推出的诸多疗法都应用了比以前更大剂量、更多种类甚至更长疗程的抗生素,这对于肠道微生物的微生态结构和数量都可能造成严重影响,甚至可能产生严重的副作用,同时也可能会对其耐药性产生影响。本文回顾了近20年来幽门螺杆菌根除治疗对肠道微生态的影响和一些新型实验疗法的研究结果,以对上述问题进行探讨。     

益生菌对幽门螺杆菌根除后肠道微生物群分布的影响

目的 检验益生菌对幽门螺杆菌根除后肠道微生物群分布的影响。方法 病人分为三联疗法根除组（A组）和三联疗法根除+双歧杆菌三联活菌胶囊联用组（B组）。治疗14天后对病人治疗效果进行多方面评估。收集治疗后患者的粪便样本进行qPCR分析,检测大肠埃希菌、肠球菌、肺炎克雷伯菌、乳杆菌、双歧杆菌及嗜热链球菌的数量。结果 120例患者中有112例按方案完成治疗,完成率为93.3%。A组患者中失访2例,不耐受5例,治疗完成率为88.3%;B组患者中失访3例,不耐受4例,治疗完成率为88.3%。双歧杆菌三联活菌胶囊降低了患者的不良反应并提高了三联疗法根除的治愈率。A组大肠杆菌及肺炎克雷伯菌相对表达水平明显高于B组;然而B组粪肠球菌、双歧杆菌、乳酸杆菌及嗜热链球菌表达高于A组。结论 益生菌的使用对提高三联疗法根除幽门螺杆菌有促进作用。     

益生菌对腹痛儿童幽门螺杆菌根除的影响

目的观察微生态制剂金双歧(双歧杆菌、乳杆菌和嗜热链球菌三联活茵片)对腹痛儿童幽门螺杆菌根除治疗的影响。方法将54例幽门螺杆菌(H.pylori)阳性的腹痛儿童随机分成A组(奥美拉唑、克拉霉素、阿莫西林三联疗法)和B组(金双歧联用三联疗法),疗程均为2周,治疗结束4周后复查13C-尿素呼气试验,统计患儿治疗期间的不良反应。结果 A、B两组根除根除率分别为74.3%和88.8%,差异无统计学意义(P>0.05);B组胃肠道不良反应明显少于A组(P<0.01)。结论微生态制剂不能显著增加腹痛儿童幽门螺杆菌根除率,但降低三联根除疗法的胃肠道不良反应。     

酪酸梭菌活菌胶囊联合标准四联疗法 清除幽门螺杆菌感染的临床研究

目的评估酪酸梭菌活菌胶囊(阿泰宁)联合标准四联疗法清除幽门螺杆菌的临床疗效。方法收集2017年1月至2018年1月就诊于甘肃省人民医院消化科门诊,经胃镜及尿素-14 C呼气试验检查诊断为幽门螺杆菌感染的慢性胃炎患者220例为研究对象并随机分为两组。其中对照组患者给予标准四联疗法,疗程2周。观察组患者在标准四联疗法基础上加用酪酸梭菌活菌胶囊,疗程2周。停药1个月后复查尿素-14 C呼气试验,分析患者临床疗效和不良反应发生率。结果 (1)观察组患者幽门螺旋杆菌清除率(88.18%)明显高于对照组(76.36%),差异有统计学意义(P0.05)。(2)观察组的不良反应发生率(8.18%)低于对照组(26.37%),差异有统计学意义(P0.05)。结论酪酸梭菌活菌胶囊联合标准四联疗法清除幽门螺杆菌的疗效显著,值得临床推广。     

A comparison between sequential therapy and a modified bismuth-based quadruple therapy for Helicobacter pylori eradication in Iran: a randomized clinical trial

Background: Sequential regimens have been recently reported to be superior to the standard triple therapies in Helicobacter pylori eradication, but most of these studies were performed in Europe and data from developing countries are lacking. So we designed a study to compare a sequential regimen with a bismuth‐based quadruple therapy that contains a short course of furazolidone, in Iran. Methods: Two hundred and ninety‐six patients with duodenal ulcer and naïve H. pylori infection were randomized into two groups: 148 patients received (PAB‐F) pantoprazole (40 mg‐bid), amoxicillin (1 g‐bid), and bismuth subcitrate (240 mg‐bid) for 2 weeks and furazolidone (200 mg‐bid) just during the first week. And 148 patients received (PA‐CT) pantoprazole (40 mg‐bid) for 10 days, amoxicillin (1 g‐bid) for the first 5 days, and clarithromycin (500 mg‐bid) plus tinidazole (500 mg‐bid) just during the second 5 days. C¹⁴‐urea breath test was performed 8 weeks after the treatment. Results: Two hundred and sixty‐one patients completed the study (137 patients in the PA‐CT and 124 in the PAB‐F group). The results were not statistically different between the two groups in the eradication rates and the severity of side effects. The intention to treat eradication rate was 80.4% in the PAB‐F group and 83.7% in the PA‐CT group. Per‐protocol eradication rates were 88.7% and 89.1%, respectively. Conclusion: Because the two regimens showed acceptable and similar abilities in H. pylori eradication and because of much higher cost of clarithromycin in Iran, the furazolidone containing regimen seems to be superior. Further modifications of sequential therapies are needed to make them ideal regimens in developing countries.     

A modified bismuth-containing quadruple therapy including a short course of furazolidone for Helicobacter pylori eradication after sequential therapy failure

Background: Helicobacter pylori eradication has still remained a challenge, especially in case of failure to novel treatments. Therefore, we designed a study to evaluate the effects of a modified bismuth‐containing quadruple therapy including a short course of furazolidone on a group of patients whose sequential therapy had been unsuccessful. Materials and Methods: Thirty‐six H. pylori‐positive patients who had previously failed a clarithromycin‐containing sequential therapy enrolled the study. They received pantoprazole (40 mg‐bid), amoxicillin (1 g‐bid), and bismuth subcitrate (240 mg‐bid) for 2 weeks and furazolidone (200 mg‐bid) just during the first week. Eight weeks after treatment, H. pylori eradication was reassessed using C14‐urea breath test. Results: Thirty five patients completed the study. H. pylori eradication rates were 80.6% (95% CI = 67.6–93.5) and 82.9% (95% CI = 70.6–95.2) according to intention‐to‐treat and per‐protocol analyses, respectively. All patients had excellent compliance to treatment, and no one interrupted therapy owing to adverse effects. Conclusion: Regarding the eradication rate (>80%), low price, and very low adverse effects, a 2‐week bismuth‐containing quadruple regimen including a short course of furazolidone can be an encouraging regimen for second‐line H. pylori eradication in case of sequential therapy failure. Possibly, it can be improved by alterations in dose, dosing intervals, and/or duration.     

复方嗜酸乳杆菌片联合三联方案根除幽门螺杆菌的临床研究

目的探讨复方嗜酸乳杆菌片联合三联方案根除幽门螺杆菌(Helicobacter pylori,H.pylori)的疗效及不良反应。方法将143例H.pylori检测阳性的患者随机分为A1组(48例)、A2组(46例)和B组(49例)。B组给予三联方案(埃索美拉唑、阿莫西林、克拉霉素)根除H.pylori治疗,疗程10d。A1组、A2组分别在上述三联方案的基础上同时加用10d、20d的复方嗜酸乳杆菌片。治疗过程中观察并记录上述三组的不良反应发生情况,停药4周后查13 C呼气试验判别H.pylori根除是否成功。结果共133例患者完成治疗和随访,A1组、A2组、B组根除率按方案(PP)分析分别为65.9%、69.8%、63.0%,按意向性(ITT)分析分别为60.4%、65.2%、59.2%,无论按方案分析还是意向性分析三组根除率差异均无统计学意义(P0.05)。纳入三组的共143例患者均完成不良反应的随访,A1组、A2组、B组不良反应发生率分别为10.4%、8.7%、30.6%,三组相比差异有统计学意义(P0.05),其中A1组、A2组分别与B组相比差异有统计学意义(P0.05),A1组与A2组相比差异无统计学意义(P0.05)。结论三联方案加用10d、20d的复方嗜酸乳杆菌片未能提高H.pylori根除率,但可降低不良反应发生率。     

Double-dose, new-generation proton pump inhibitors do not improve Helicobacter pylori eradication rate

BACKGROUND: Up to present, omeprazole plus two antibiotics are used for Helicobacter pylori eradication therapy . Few studies have compared double-dose new-generation, proton pump inhibitors (PPI) with omeprazole. Therefore, we conducted a randomized, prospective study to evaluate differences in H. pylori eradication rates by PPI type. MATERIAL AND METHODS: Between January 2006 and December 2006, 576 consecutive patients with proven H. pylori infection were enrolled prospectively. Four different PPIs [omeprazole 20 mg b.i.d. (old generation), or pantoprazole 40 mg b.i.d., rabeprazole 20 mg b.i.d., or esomeprazole 40 mg b.i.d. (new generation)] were added to clarithromycin (500 mg b.i.d.) and amoxicillin (1 g b.i.d.) for 1 week. RESULTS: By intention-to-treat analysis, no difference was found between the eradication rates of these four PPIs: 64.9% (omeprazole, n = 148), 69.3% (pantoprazole, n = 140), 69.3% (rabeprazole, n = 140), and 72.9% (esomoprazole, n = 148). When eradication rates were analyzed according to whether patients had an ulcer or not on a per-protocol basis, no difference was found between the eradication rates of the four PPIs. However, side-effects were more common in the esomeprazole-based triple therapy group than in the other groups (p < .05). CONCLUSIONS: No convincing evidence was obtained that double-dose new-generation PPIs have better H. pylori eradication rates and tolerability than omeprazole.     

益生菌联合铋剂四联法根除幽门螺杆菌的Meta分析和试验序贯分析

采用Meta分析和试验序贯分析的方法评估益生菌辅助铋剂四联法根除幽门螺杆菌的有效性和安全性。

检索PubMed、the Cochrane Library、Embase、Web of Science、中国知网、维普数据库、万方、中国生物医学数据库, 检索时限均从数据库建立至2021年3月, 对公开发表的关于益生菌联合铋剂四联法根除幽门螺杆菌的随机对照双盲试验进行Meta分析和试验序贯分析。

共纳入6项研究, 总样本量1 462例。与铋剂四联法相比, 益生菌联合铋剂四联法能有效提高幽门螺杆菌根除率[RR=1.15, 95%CI=(1.03, 1.29), P=0.02], 并显著降低不良反应率[RR=0.45, 95%CI=(0.25, 0.82), P=0.01], TSA显示其结果均具有确切的结论性。Harbord回归显示不存在显著发表偏倚。GRADE证据质量评价显示, 幽门螺杆菌根除率、恶心、腹泻、味觉异常的证据质量均为中, 不良反应率、呕吐、腹痛、便秘、腹胀、厌食、疲劳、头晕的证据质量为低。

益生菌联合铋剂四联法是根除幽门螺杆菌更为安全有效的治疗方案, 具有进一步研究探索的价值。

     

Helicobacter pylori infection and immune thrombocytopenic purpura: an update

Data are accumulating on the association between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) and the significant increase in platelet count after bacterial eradication. The aim of this review was to consider the studies so far published on H. pylori infection and ITP in order to evaluate a possible correlation between these two conditions. A review of the literature showed that 278 out of the 482 ITP patients investigated (58%) were positive for H. pylori infection and that the bacterium was eradicated in 88% of cases. Eradication therapy was accompanied by a complete or partial platelet response in approximately half the cases. Overall, these data show that H. pylori eradication in patients with ITP is effective in increasing platelet count. However, because the studies so far published are few, are sometimes controversial and involve small series of patients, further studies on larger numbers of patients with longer follow-up are needed to confirm these preliminary findings.     

布拉酵母菌联合三联疗法根除幽门螺杆菌疗效研究

目的探讨布拉酵母菌（S．Boulardii）散剂联合标准三联疗法根除幽门螺杆菌（Helicobacterpylori,H．pylori）的有效性和安全性。方法将210例初次接受根除治疗的Hpylori阳性患者随机分为2组,A组：口服埃索美拉唑＋阿莫西林＋呋喃唑酮,每日2次,疗程10d;B组：与A相同的三联10d疗法,加s．Boulardii散剂口服500mg／次,2次／d,共用药14d。观察患者不良反应发生情况及对药物耐受情况,停药4周后检测H．pylori根除率。结果A、B组Hpylori根除率按方案（PP）分析分别为70．7％、86．3％,按意向性（ITT）分析分别为66．7％、83．8％,B组PP和ITT根除率均高于A组,差异有统计学意义（P〈0．05）;B组不良反应发生率低于A组（8．8％vs 28．3％,P〈0．05）;在药物耐受程度方面,B组明显优于A组（P〈0．05）。结论S．Boulardii散剂联合标准三联疗法作为初次根除Hpylori治疗时可提高根除率,降低不良反应,增加药物耐受程度。     

Efficacy and safety of faropenem in eradication therapy of Helicobacter pylori

Aims: While triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin is the standard therapy for Helicobacter pylori eradication, it is ineffective against clarithromycin‐resistant strains. To seek a better regimen for eradication therapy, we assessed the sensitivity of clinical strains seen in Japan to faropenem and then evaluated the efficacy and safety of eradication therapy containing this antibiotic. Methods: Minimum inhibitory concentrations (MICs) of faropenem were determined in 78 Japanese clinical H. pylori isolates using the agar dilution method. H. pylori‐positive patients were consecutively assigned to a 7‐day eradication therapy protocol with LAF (lansoprazole 60 mg/day, amoxicillin 2000 mg/day, and faropenem 600 mg/day), and then to a 14‐day protocol. The outcomes of the therapies were assessed by ¹³C‐urea breath tests. Results: All 78 strains showed MICs of faropenem that were equal to or less than 0.2 µg/mL. The eradication rates according to intention‐to‐treat analyses were 46.5% with the 7‐day therapy (n = 43) and 62.5% with the 14‐day therapy (n = 32). No special measures were required to treat the adverse events observed in approximately one‐third of the patients. Conclusions: Faropenem was found to have good antimicrobial action against H. pylori in vitro. The 14‐day LAF therapy successfully eradicated H. pylori in about two‐thirds of the patients although the incidence of adverse events was high.     

益生菌对幽门螺杆菌阳性消化性溃疡治疗有效性的Meta分析

目的 探讨益生菌+H.pylori标准疗法对消化性溃疡患者H.pylori感染的根除率与安全性。 方法 计算机检索2019年3月20日以前公开发表的中英文数据库文献(知网数据库、万方数据库、EMBASE数据库、MEDLINE数据库以及PubMed数据库等),借助RevMan 5.2软件分析与评价相关数据。 结果 检索符合条件研究文献共11篇。Meta分析证实,益生菌+H.pylori标准治疗方案可以有效提高H.pylori根除率(OR=2.94,P结论 益生菌+H.pylori标准疗法对消化性溃疡患者H.pylori感染的根除率以及溃疡愈合好转率均有提升,并显著降低不良反应发生率,具备临床推广价值。