Meta-Analysis: The Effect of Supplementation with Lactoferrin on Eradication Rates and Adverse Events During Helicobacter pylori Eradication Therapy

Background: Recent evidence shown that lactoferrin could exert an antimicrobial effect against Helicobacter pylori both in vitro and in vivo models. To systematically evaluate whether adding lactoferrin to H. pylori eradication regimens could improve eradication rates and reduce side-effects during anti- H. pylori treatment.
Materials and Methods:  Eligible articles were identified by searches of electronic databases. We included all randomized trials comparing lactoferrin supplementation to placebo or no treatment during anti- H. pylori regimens. Statistical analysis was performed with Review Manager 5.0.10. Subanalysis/Sensitivity analysis was also performed.
Results: We identified nine randomized trials (n = 1343). Pooled H. pylori eradication rates were 86.57% (95% confidence interval (CI) = 83.99–89.15%) and 74.44% (95% CI = 71.14–77.74%) for patients with or without lactoferrin by intention-to-treat analysis, respectively, the odds ratio (OR) was 2.26 (95% CI = 1.70–3.00); the occurrence of total side-effects was 9.05% (95% CI = 6.83–11.27%) and 16.28% (95% CI = 13.43%–19.13%) for groups with or without lactoferrin, especially for nausea, the summary OR was 0.15 (95% CI = 0.04–0.54).
Conclusions: Our review suggests that supplementation with lactoferrin could be effective in increasing eradication rates of anti- H. pylori therapy, and could be considered helpful for patients with eradication failure. Furthermore, lactoferrin shows a positive impact on H. pylori therapy-related side-effects.     

The Effect of Probiotics and Mucoprotective Agents on PPI‐Based Triple Therapy for Eradication of Helicobacter pylori

Background/Aims: Recent studies have found that probiotics have anti‐Helicobacter pylori (HP) properties. We evaluated the additive effects of (i) Saccharomyces boulardii combined with proton pump inhibitor (PPI)‐based triple therapy and (ii) S. boulardii and a mucoprotective agent (DA‐9601) coupled with PPI‐based triple therapy for HP eradication. Methods: We recruited 991 HP infected patients and randomized them into one of three groups, (A) PPI‐based 7‐day triple therapy, (B) the same triple therapy plus S. boulardii for 4 weeks, and (C) the same 7‐day triple therapy plus S. boulardii and mucoprotective agent for 4 weeks. All patients in the three groups were tested via ¹³C‐urea breath test 4 weeks after the completion of the therapy. Results: According to the results of an intention‐to‐treat analysis, HP eradication rates for the groups A, B, and C were 71.6% (237/331), 80.0% (264/330), and 82.1% (271/330), respectively (p = .003). According to the results of a per protocol analysis, the eradication rates were 80.0% (237/296), 85.4% (264/309) and, 84.9% (271/319), respectively (p = .144). The frequency of side effects in group B (48/330) and C (30/330) was lower than that in group A (63/331) (p < .05). Conclusion: This study suggests that supplementation with S. boulardii could be effective for improving HP eradication rates by reducing side effects thus helping completion of eradication therapy. However, there were no significant effects on HP eradication rates associated with the addition of mucoprotective agents to probiotics and triple therapy.     

Meta-Analysis: Lactobacillus Containing Quadruple Therapy Versus Standard Triple First-Line Therapy for Helicobacter pylori Eradication

Background:  Recent evidence showed that Lactobacilli could exert an inhibitory effect on Helicobacter pylori both in vitro and in vivo models. To systematically evaluate whether adding Lactobacilli to H. pylori eradication regimens could improve eradication rates and reduce side effects during anti- H. pylori treatment.
Materials and Methods:  Eligible articles were identified by searches of electronic databases. We included all randomized trials comparing Lactobacilli supplementation to placebo or no treatment during anti- H. pylori regimens. Statistical analysis was performed with Review Manager 5.0.10. Subanalysis analysis was also performed.
Results:  We identified eight randomized trials (n = 1372). Pooled H. pylori eradication rates were 82.26% (95% CI = 78.01–86.51%) and 76.97% (95% CI = 73.11–80.83%) for patients with or without Lactobacilli by intention-to-treat analysis, respectively, the odds ratio (OR) was 1.78 (95% CI = 1.21–2.62). The occurrence of total side effects had no significant difference and were 30.84% (95% CI = 24.82–36.86%) and 42.24% (95% CI = 35.89%–48.59%) for two groups, the summary OR was 0.49 (95% CI = 0.24–1.02); However, Lactobacilli supplementation group had lower occurrence of diarrhoea, bloating and taste disturbance.
Conclusions:  Our review suggests that supplementation with Lactobacilli could be effective in increasing eradication rates of anti- H. pylori therapy for first-treated patients. Furthermore, Lactobacilli showed a positive impact on some H. pylori therapy-related side effects.     

Levofloxacin-Based First-Line Therapy versus Standard First-Line Therapy for Helicobacter pylori Eradication: Meta-Analysis of Randomized Controlled Trials

Background

First-line levofloxacin-based treatments eradicate Helicobacter pylori with varying success. We examined the efficacy and safety of first-line levofloxacin-based treatment in comparison to standard first-line therapy for H pylori eradication.

Materials and Methods

We searched literature databases from Medline, EMBASE, and the Cochrane Register of Randomized Controlled Trials through March 2013 for randomized controlled trials comparing first-line levofloxacin and standard therapy. We included randomized controlled trials conducted only on naïve H pylori infected patients in adults. A systematic review was conducted. Meta-analysis was performed with Review Manager 5.2. Treatment effect was determined by relative risk with a random or fixed model by the Mantel-Haenszel method.

Results

Seven trials were identified with 888 patients receiving 7 days of first-line levofloxacin and 894 treated with standard therapy (Amoxicillin, Clarithromycin and proton pump inhibitor) for 7 days. The overall crude eradication rate in the Levofloxacin group was 79.05% versus 81.4% in the standard group (risk ratio 0.97; 95% CI; 0.93, 1.02). The overall dropout was 46 (5.2%) in the levofloxacin group and 52 (5.8%) for standard therapy. The dizziness was more common among group who took Levofloxacin based treatment and taste disturbance was more common among group who took standard therapy. Meta-analysis of overall adverse events were similar between the two groups with a relative risk of 1.06 (95% CI 0.72, 1.57).

Conclusion

Helicobacter pylori eradication with 7 days of Levofloxacin-based first line therapy was safe and equal compared to 7 days of standard first-line therapy.     

Inhibition of Helicobacter pylori Infection in Humans by Lactobacillus reuteri ATCC 55730 and Effect on Eradication Therapy: A Pilot Study

Background:  Several studies report an inhibitory effect of probiotics on Helicobacter pylori .
Aim:  To test whether Lactobacillus reuteri ATCC 55730 reduces H. pylori intragastric load in vivo, decreases dyspeptic symptoms, and affects eradication rates after conventional treatment.
Materials and Methods:  In a double-blind placebo-controlled study, 40 H. pylori -positive subjects were given L. reuteri once a day for 4 weeks or placebo. All underwent upper endoscopy, ¹³C-urea breath test, and H. pylori stool antigen determination at entry and ¹³C-urea breath test and H. pylori stool antigen (used as both qualitative and semiquantitative markers) after 4 weeks of treatment. Sequential treatment was administered subsequently to all.
Results:  In vivo, L. reuteri reduces H. pylori load as semiquantitatively assessed by both ¹³C-urea breath test δ -value and H. pylori stool antigen quantification after 4 weeks of treatment ( p <  .05). No change was shown in patients receiving placebo. L. reuteri administration was followed by a significant decrease in the Gastrointestinal Symptom Rating Scale as compared to pretreatment value ( p <  .05) that was not present in those receiving placebo ( p =  not significant). No difference in eradication rates was observed.
Conclusions:  L. reuteri effectively suppresses H. pylori infection in humans and decreases the occurrence of dyspeptic symptoms. Nevertheless, it does not seem to affect antibiotic therapy outcome.     

Variables Influencing Outcome of Helicobacter pylori Eradication Therapy in South China

Background: Therapy combining a proton pump inhibitor (PPI), clarithromycin and either amoxicillin or metronidazole is widely recommended for first‐line treatment for Helicobacter pylori infection. The purpose of this study was to examine the outcomes of PPI‐containing triple therapy and identify factors influencing the cure rate of H. pylori infection in South China. Materials and Methods: H. pylori positive patients with different occupations from 25 hospitals in five provinces of South China were enrolled. They received a PPI, metronidazole and amoxicillin triple therapy for a week. H. pylori eradication was evaluated by ¹³C‐urea breath test 4 weeks after therapy. Association between H. pylori eradication with occupation, gender, age, educational level, and protocol compliance was evaluated by Logistic regression. Results: Six hundred and seventy‐five were enrolled. The intention‐to‐treat and per‐protocol analyses showed overall cure rates of 60% (95% CI = 56.3–63.7%) and 64.5% (95% CI = 60.7–68.3%), respectively. Multivariate logistic regression showed that occupation, gender and protocol compliance were positively associated with the eradication rate (p < .01). The cure rate for those who took 80% or more of the prescribed drugs was 64.5% (95% CI = 60.7–68.3%) versus 14.6% (95% CI = 6–29%, p < .001) for those who took less. Lower eradication rates were also observed in farmers and women. Conclusions: The eradication rate with a PPI, metronidazole and amoxicillin triple therapy was unacceptably low in South China. These results suggest that studies of the eradication of H. pylori infection in China must take into account antibiotic resistance as well as patient occupation, gender, and protocol compliance. Gastric cancer and peptic ulcer disease are both important in China making methods to effectively and efficiently eradicate H. pylori a priority.     

幽门螺杆菌根除失败后两种四联方案根除率的疗效对比

目的:对比两种不同的四联疗法对幽门螺杆菌根除失败后的根除率,选择可以有效弥补传统三联疗法的幽门螺杆菌根除失败措施的四联疗法。方法:选择2010年8月到2012年8月期间在我院住院治疗的幽门螺杆菌根除失败后患者90例作为研究对象。随机分为实验组和对照组,实验组的患者采取序贯疗法,对照组的患者采取标准四联疗法。对比两组的根除率以及临床疗效。结果:实验组患者的根除率为86.7%,对照组患者根除率为51.0%;实验组患者的临床总有效率为95.6%,对照组的临床有效率为77.8%;实验组的不良反应的总发生率为4.4%,对照组不良反应总发生率为20.0%。两组比较差异明显,P均0.05,具有统计学意义。结论:序贯疗法对幽门螺杆菌根除失败后的根除率以及疗效高于标准四联疗法。     

Interaction of Drugs for Eradication Therapy against Antibiotic-Resistant Strains of Helicobacter pylori

To clarify the interactions of drugs for combination therapy of Helicobacter pylori infection, especially due to antibiotic-resistant strains, we have evaluated the in vitro effect of combining different drugs. Using a modified time-kill assay, we tested the effect of combining 2 drugs from 4 agents; amoxicillin (AMPC), clarithromycin (CAM), metronidazole (MTZ) and lansoprazole (a proton pump inhibitor). The H. pylori in the study consisted of 4 strains sensitive to the all drugs, 2 strains resistant only to CAM, 2 strains resistant only to MTZ, and 2 strains resistant to both CAM and MTZ. From the 6 different drug combinations, synergism was observed for 5 of the combinations, among which the combination of AMPC and CAM revealed such effects most frequently. However, all of the strains which showed synergism were sensitive to both of the drugs. In the case of the strains resistant to CAM and/or MTZ, no synergism was demonstrated in any of the combinations including CAM and/or MTZ. When a strain was resistant to one drug from a combination, no synergism was detected. Thus, the administration of a drug to which the strains are resistant may have no advantage in the eradication therapy of H. pylori. For a more effective and safer therapy, susceptibility testing should be performed before treatment.     

The Clinical and Bacteriological Factors for Optimal Levofloxacin-Containing Triple Therapy in Second-Line Helicobacter pylori Eradication

Quinolone has the disadvantage of easily acquired drug resistance. It is important to prescribe it wisely for a high eradication rate. The current study aimed to determine the clinical and bacteriological factors for optimal levofloxacin-containing triple therapies in second-line H. pylori eradication. We enrolled a total of 158 H. pylori-infected patients who failed H. pylori eradication using the 7-day standard triple therapy (proton-pump inhibitor [PPI] twice daily, 500 mg clarithromycin twice daily, and 1 g amoxicillin twice daily). They were prescribed with either a 10-day (group A) or 14-day (group B) levofloxacin-containing triple therapy group (levofloxacin 500 mg once daily, amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily for 10 days) by their clinicians. Follow-up studies to assess treatment responses were carried out 8 weeks later. The eradication rates attained by groups A and B were 73.6% (95% confidence interval [CI] = 63.9–85.3%) and 90.5% (95% CI = 84.5–98.1%), respectively in the per protocol analysis (P = 0.008 in the per protocol analysis) and 67.1% (95% CI = 56.6–78.5%) and 84.8% (95% CI = 76.8–93.4%), respectively, in the intention-to-treat analysis (P = 0.009). The subgroup analysis revealed that H. pylori eradication rates for group A patients with levofloxacin-susceptible strains were 92.9% (13/14) but it dropped to 12.5% (1/8) when levofloxacin-resistant strains existed. H. pylori was eradicated among all the group B patients with levofloxacin-susceptible strains, but only half of patients with levofloxacin-resistant strains were successfully eradicated. In conclusion, this study confirms the effectiveness of 14-day treatment. Importantly, the results imply that 10-day treatment duration should be optimal if a culture can be performed to confirm the existence of susceptible strains. The duration of H. pylori eradication and levofloxacin resistance were the influencing factors for successful treatment. This study suggests that tailored levofloxacin-containing therapy should be administered only for patients with susceptible strains because it can achieve >90% success rates.     

Helicobacter pylori Eradication on the Prevention of Metachronous Lesions after Endoscopic Resection of Gastric Neoplasm: A Meta-Analysis

Background

There is controversy about the effect of Helicobacter pylori (H. pylori) eradication on the prevention of metachronous gastric cancer after endoscopic resection (ER).

Aims

The aim of this study was to systematically evaluate the effect of H. pylori eradication on the prevention of metachronous gastric lesions after ER of gastric neoplasms.

Methods

We performed a systematic search of PubMed, EMBASE, the Cochrane Library, and MEDLINE that encompassed studies through April 2014. Our meta-analysis consisted of 10 studies, which included 5881 patients who underwent ER of gastric neoplasms.

Results

When we compared the incidence of metachronous lesions between H. pylori-eradicated and non-eradicated groups, H. pylori eradication significantly lowered the risk of metachronous lesions after ER of gastric neoplasms (five studies, OR = 0.392, 95% CI 0.259 – 0.593, P < 0.001). When we compared H. pylori-eradicated and persistent groups, again, H. pylori eradication significantly lowered the incidence of metachronous lesions after ER of gastric neoplasms (six studies, OR = 0.468, 95% CI 0.326 – 0.673, P < 0.001). There was no obvious heterogeneity across the analyzed studies.

Conclusions

This meta-analysis suggests a preventive role for H. pylori eradication for metachronous gastric lesions after ER of gastric neoplasms. Thus, H. pylori eradication should be considered if H. pylori infection is confirmed during ER.     

黄连素四联方案补救治疗幽门螺杆菌感染的有效性和安全性

目的:探索黄连素四联方案用于幽门螺杆菌感染根除失败患者补救治疗的有效性及安全性。方法:将经四联方案初次根除治疗失败并自愿接受补救治疗的130例患者按纳入顺序,以1:1的比例分配治疗,随机接受14天黄连素四联(埃索美拉唑20mg+胶体果胶铋200 mg+阿莫西林1000 mg,2/d+黄连素300 mg 3/d)或四环素四联(埃索美拉唑20 mg+胶体果胶铋200 mg+四环素750 mg+呋喃唑酮100 mg,2/d)方案的治疗。所有患者均于治疗14天及治疗结束至少28天后随诊,详细记录患者症状及不良反应情况。治疗结束至少28天后进行13C尿素呼气试验来判断幽门螺杆菌根除情况。结果:65例接受黄连素四联根除治疗,65例接受四环素四联方案治疗。两组分别有6例和4例患者因不良反应服药依从性小于80%,其余患者均完成了14天的治疗。黄连素组和四环素组的幽门螺杆菌根除率ITT分析分别为76.9%(50/65)和81.5%(53/65),P=0.520;PP分析分别为84.7%(50/59)和86.9%(53/61),P=0.739。黄连素组和四环素组不良事件总体发生率分别为49.2%和41.5%,P=0.370。结论:黄连素四联疗法用于幽门螺杆菌感染的二次根除治疗,根除率较高,未明显增加不良事件发生率,是有效及安全的补救治疗方案。