Non-improvement of atrophic gastritis in cases of gastric cancer after successful Helicobacter pylori eradication therapy

BACKGROUND Helicobacter pylori(H.pylori)infection is closely related to the development of gastric cancer(GC).However,GC can develop even after H.pylori eradication.Therefore,it would be extremely useful if GC could be predicted after eradication.The Kyoto classification score for gastritis(GA)is closely related to cancer risk.However,how the score for GC changes after eradication before onset is not well understood.AIM To investigate the characteristics of the progression of Kyoto classification scores for GC after H.pylori eradication.METHODS Eradication of H.pylori was confirmed in all patients using either the urea breath test or the stool antigen test.The Kyoto classification score of GC patients was evaluated by endoscopy at the time of event onset and three years earlier.In ad-dition,the modified atrophy score was evaluated and compared between the GC group and the control GA group.RESULTS In total,30 cases of early GC and 30 cases of chronic GA were evaluated.The pathology of the cancer cases was differentiated adenocarcinoma,except for one case of undifferentiated adenocarcinoma.The total score of the Kyoto classifi-cation was significantly higher in the GC group both at the time of cancer onset and three years earlier(4.97 vs 3.73,P=0.0034;4.2 vs 3.1,P=0.0035,respectively).The modified atrophy score was significantly higher in the GC group both at the time of cancer onset and three years earlier and was significantly improved only in the GA group(5.3 vs 5.3,P=0.5;3.73 vs 3.1,P=0.0475,respectively).CONCLUSION The course of the modified atrophy score is useful for predicting the onset of GC after eradication.Patients with severe atrophy after H.pylori eradication require careful monitoring.

Susceptibility patterns and virulence genotypes of Helicobacter pylori affecting eradication therapy outcomes among Egyptian patients with gastroduodenal diseases

BACKGROUND Helicobacter pylori(H.pylori)is a significant human pathogen that is responsible for a variety of illnesses,including mucosa-associated lymphoid tissue lymphoma,gastric cancer,peptic ulcers,and gastritis.AIM To investigate the frequency of H.pylori infection and its resistance patterns among Egyptian patients and to determine the influence of H.pylori virulence genetic determinants on the eradication success of 14-d triple therapy regimen.METHODS H.pylori infections were investigated in 72 patients with gastroduodenal complications suggestive of H.pylori infection.The cagA and vacA genotypes of cultured strains were studied using polymerase chain reaction.The patients underwent 14 d of triple-therapy treatment.The treatment response was examined using histology and a rapid urease test 6 wk after therapy discontinuation.RESULTS The intention-to-treat eradication rate was 59.2%(95%CI:48.2%-70.3%).Rates of H.pylori resistance to clarithromycin,amoxicillin,and metronidazole were 52.8%,81.9%,and 100%,respectively.Successful eradication of H.pylori was more significantly associated with vacA s1-positive strains[adjusted odds ratio(aOR)=0.507,95%CI:0.175-0.822].A significant association was found between failed eradication rate and H.pylori strains resistant to clarithromycin(aOR=0.204,95%CI:-0.005 to 0.412)and amoxicillin(aOR=0.223,95%CI:0.026-0.537).CONCLUSION This study’s low H.pylori eradication rate following 14-d triple therapy is concerning and worrying.H.pylori pan-resistance to metronidazole followed by the high resistance to ciprofloxacin,amoxicillin,and clarithromycin in this research is challenging and of great concern.

Role of high-dose amoxicillin dual therapy for Helicobacter pylori eradication in an Irish cohort:A prospective study

Helicobacter pylori(H.pylori)infections may cause chronic gastritis,peptic ulcer disease,gastric cancers,and other conditions outside of the gastrointestinal tract.Hence,it is important to diagnose and treat it early.H.pylori is resistant to certain drugs in traditional eradication therapy,so alternative therapy protocols are needed,such as high-dose amoxicillin dual therapy(HDADT).This article aims to comment on a recent paper by Costigan et al in the World Journal of Clinical Cases.In this study,the authors recruited 139 patients diagnosed with H.pylori,all treated with HDADT.Of these,93 were treatment-naïve and 46 had received at least one alternative treatment in the past.Four weeks after the end of the treatment,the urea breath test was administered to estimate the eradication rate.The total eradication rate was 56%(78/139),62%for the treatment-naïve arm and 43%for the previous treatment arm,thus indicating a lower success rate for the arm that had previously received a different treatment regimen.In conclusion,a therapeutic approach with first-line HDADT may potentially be a better treat-ment,but the results are not sufficient to recommend the use of this regimen in a country with high levels of dual resistance.

Efficacy of tailored Helicobacter pylori eradication therapy based on antibiotic susceptibility and CYP2C19 genotype

The cure rates of Helicobacter pylori (H. pylori) eradication therapy using a proton pump inhibitor (PPI) and antimicrobial agents such as amoxicillin, clarithromycin, and metronidazole are mainly influenced by bacterial susceptibility to antimicrobial agents and the magnitude of the inhibition of acid secretion. Annual cure rates have gradually decreased because of the increased prevalence of H. pylori strains resistant to antimicrobial agents, especially to clarithromycin. Alternative regimens have therefore been developed incorporating different antimicrobial agents. Further, standard PPI therapy (twice-daily dosing) often fails to induce a long-term increase in intragastric pH > 4.0. Increasing the eradication rate requires more frequent and higher doses of PPIs. Therapeutic efficacy related to acid secretion is influenced by genetic factors such as variants of the genes encoding drug-metabolizing enzymes (e.g., cytochrome P450 2C19, CYP2C19), drug transporters (e.g., multidrug resistance protein-1; ABCB1), and inflammatory cytokines (e.g., interleukin-1β). For example, quadruple daily administration of PPI therapy potently inhibits acid secretion within 24 h, irrespective of CYP2C19 genotype. Therefore, tailored H. pylori eradication regimens that address acid secretion and employ optimal antimicrobial agents based on results of antimicrobial agent-susceptibility testing may prove effective in attaining higher eradication rates.

Does Helicobacter pylori eradication therapy for peptic ulcer prevent gastric cancer?

AIM:To investigate the effects of Helicobacter pylori (H pylori)eradication therapy for treatment of peptic ulcer on the incidence of gastric cancer. METHODS:A multicenter prospective cohort study was conducted between November 2000 and December 2007 in Yamagata Prefecture,Japan.The study included patients with H pylori-positive peptic ulcer who decided themselves whether to receive H pylori eradication(eradication group)or conventional antacid therapy(non-eradication group).Incidence of gastric cancer in the two groups was determined based on the results of annual endoscopy and questionnaire surveys,as well as Yamagata Prefectural Cancer Registry data,and was compared between the two groups and by results of H pylori therapy.RESULTS:A total of 4133 patients aged between 13 and 91 years(mean 52.9 years)were registered,and 56 cases of gastric cancer were identified over a mean follow-up of 5.6 years.The sex-and age-adjusted incidence ratio of gastric cancer in the eradication group, as compared with the non-eradication group,was 0.58 (95%CI:0.28-1.19)and ratios by follow-up period(<1 year,1-3 years,>3 years)were 1.16(0.27-5.00),0.50 (0.17-1.49),and 0.34(0.09-1.28),respectively.Longer follow-up tended to be associated with better prevention of gastric cancer,although not to a significant extent.No significant difference in incidence of gastric cancer was observed between patients with successful eradication therapy(32/2451 patients,1.31%)and those with treatment failure(11/639 patients,1.72%).Among patients with duodenal ulcer,which is known to be more prevalent in younger individuals,the incidence of gastric cancer was significantly less in those with successful eradication therapy(2/845 patients,0.24%)than in those with treatment failure(3/216 patients,1.39%). CONCLUSION:H pylori eradication therapy for peptic ulcer patients with a mean age of 52.9 years at registration did not significantly decrease the incidence of gastric cancer.

Effect of gastric microbiota on quadruple Helicobacter pylori eradication therapy containing bismuth

BACKGROUND Helicobacter pylori(H.pylori)is an important pathogen that can cause a variety of diseases.Yet,full eradication of H.pylori remains a significant challenge in clinical practice.H.pylori and other microbial communities have complex interactions in the unique gastric microecological environment.However,it is not clear whether the interactions have any effect on the therapeutic effect of H.pylori.AIM The aim was to investigate the characteristics of the gastric microbiota with H.pylori infection and the influence on the H.pylori eradication treatment.METHODS Patients with H.pylori infection underwent gastroscopy and received treatment for eradication.The prescription included esomeprazole 20 mg bid,Livzon Dele 220 mg bid,amoxicillin 1000 mg bid,and clarithromycin 500 mg bid for 14 d.Patients who did not respond to treatment and failed eradication were compared with those who achieved eradication by 1:2 propensity matching.Highthroughput sequencing of the gastric mucosal microbiota was performed,and the results were evaluated by alpha diversity analysis,beta diversity analysis,species correlation analysis,and metabolic pathway correlation analysis.RESULTS The eradication rate of all the patients was 95.5%(171/179).Twenty-four patients were enrolled in the study after propensity-matched scoring.There were eight cases in the failure group(patients who did not respond well to therapy)and 16 cases in the success group.The majority phyla in the two groups were the same,and included Proteobacteria,Bacteroides,Firmicutes,Actinomycetes,and Fusobacteria.The microbial diversity in the failure group had a decreasing trend(P=0.092)and the species abundance was significantly lower(P=0.031)compared with the success group.The high rate of H.pylori eradication was associated with Rhodococcus,Lactobacillus,and Sphingomonas,as they were significantly enriched in the successful group(P<0.05).Veronococcus and Cilium were enriched in the mucosa of chronic atrophic gastritis patients compared with chronic superficial gastritis patients(P=0.0466 and 0.0122,respectively).In both study groups,H.pylori was negatively correlated with other bacterial genera.More bacterial genera were directly related to H.pylori in the successful group compared with the failure group.CONCLUSION The effectiveness of quadruple H.pylori eradication therapy containing bismuth depended on gastric microbiota,and the high rate of H.pylori eradication was associated with the presence of Rhodococcus,Lactobacillus,and Sphingomonas.

Rabeprazole, clarithromycin, and amoxicillin Helicobacter pylori eradication therapy: Report of an efficacy study

AIM: To investigate the efficacy of a standard triple therapy (comprising rabeprazole, clarithromycin, and amoxicillin) for Helicobacter pylori (H. pylori) eradication, noting factors that influence the outcome and documenting any adverse events.

Helicobacter pylori:High dose amoxicillin does not improve primary or secondary eradication rates in an Irish cohort

BACKGROUND Helicobacter pylori(H.pylori)eradication rates have fallen globally,likely in large part due to increasing antibiotic resistance to traditional therapy.In areas of high clarithromycin and metronidazole resistance such as ours,Maastricht VI guidelines suggest high dose amoxicillin dual therapy(HDADT)can be considered,subject to evidence for local efficacy.In this study we assess efficacy of HDADT therapy for H.pylori eradication in an Irish cohort.AIM To assess the efficacy of HDADT therapy for H.pylori eradication in an Irish cohort as both first line,and subsequent therapy for patients diagnosed with H.pylori.METHODS All patients testing positive for H.pylori in a tertiary centre were treated prospectively with HDADT(amoxicillin 1 g tid and esomeprazole 40 mg bid×14 d)over a period of 8 months.Eradication was confirmed with Urea Breath Test at least 4 wk after cessation of therapy.A delta-over-baseline>4%was considered positive.Patient demographics and treatment outcomes were recorded,analysed and controlled for basic demographics and prior H.pylori treatment.RESULTS One hundred and ninety-eight patients were identified with H.pylori infection,10 patients were excluded due to penicillin allergy and 38 patients refused follow up testing.In all 139 were included in the analysis,55%(n=76)were female,mean age was 46.6 years.Overall,93(67%)of patients were treatment-naïve and 46(33%)had received at least one previous course of treatment.The groups were statistically similar.Self-reported compliance with HDADT was 97%,mild side-effects occurred in 7%.There were no serious adverse drug reactions.Overall the eradication rate for our cohort was 56%(78/139).Eradication rates were worse for those with previous treatment[43%(20/46)vs 62%(58/93),P=0.0458,odds ratio=2.15].Age and Gender had no effect on eradication status.CONCLUSION Overall eradication rates with HDADT were disappointing.Despite being a simple and possibly better tolerated regime,these results do not support its routine use in a high dual resistance country.Further investigation of other regimens to achieve the>90%eradication target is needed.

Vonoprazan-amoxicillin dual regimen with Saccharomyces boulardii as a rescue therapy for Helicobacter pylori:Current perspectives and implications

Yu et al’s study in the World Journal of Gastroenterology(2023)introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with Saccharomyces boulardii(S.boulardii)for the rescue therapy against Helicobacter pylori(H.pylori),a pathogen responsible for peptic ulcers and gastric cancer.Vonoprazan is a potassium-competitive acid blocker renowned for its rapid and long-lasting acid suppression,which is minimally affected by mealtime.Compared to proton pump inhibitors,which bind irreversibly to cysteine residues in the H+/K+-ATPase pump,Vonoprazan competes with the K+ions,prevents the ions from binding to the pump and blocks acid secretion.Concerns with increasing antibiotic resistance,effects on the gut microbiota,patient compliance,and side effects have led to the advent of a dual regimen for H.pylori.Previous studies suggested that S.boulardii plays a role in stabilizing the gut barrier which improves H.pylori eradication rate.With an acceptable safety profile,the dual-adjunct regimen was effective regardless of prior treatment failure and antibiotic resistance profile,thereby strengthening the applicability in clinical settings.Nonetheless,S.boulardii comes in various formulations and dosages,warranting further exploration into the optimal dosage for supplementation in rescue therapy.Additionally,larger,randomized,double-blinded controlled trials are warranted to confirm these promising results.

Chemoprevention of gastric cancer development after Helicobacter pylori eradication therapy in an East Asian population:Meta-analysis

BACKGROUND Helicobacter pylori(H.pylori)infection is a risk factor for gastric cancer(GC),especially in East Asian populations.Most East Asian populations infected with H.pylori are at higher risk for GC than H.pylori-positive European and United States populations.H.pylori eradication therapy reduces gastric cancer risk in patients after endoscopic and operative resection for GC,as well as in non-GC patients with atrophic gastritis.AIM To clarify the chemopreventive effects of H.pylori eradication therapy in an East Asian population with a high incidence of GC.METHODS PubMed and the Cochrane library were searched for randomized control trials(RCTs)and cohort studies published in English up to March 2019.Subgroup analyses were conducted with regard to study designs(i.e.,RCTs or cohort studies),country where the study was conducted(i.e.,Japan,China,and South Korea),and observation periods(i.e.,≤5 years and>5 years).The heterogeneity and publication bias were also measured.RESULTS For non-GC patients with atrophic gastritis and patients after resection for GC,4 and 4 RCTs and 12 and 18 cohort studies were included,respectively.In RCTs,the median incidence of GC for the untreated control groups and the treatment groups was 272.7(180.4–322.4)and 162.3(72.5–588.2)per 100000 person-years in non-GC cases with atrophic gastritis and 1790.7(406.5–2941.2)and 1126.2(678.7–1223.1)per 100000 person-years in cases of after resection for GC.Compared with non-treated H.pylori-positive controls,the eradication groups had a significantly reduced risk of GC,with a relative risk of 0.67[95%confidence interval(CI):0.47–0.96]for non-GC patients with atrophic gastritis and 0.51(0.36–0.73)for patients after resection for GC in the RCTs,and 0.39(0.30–0.51)for patients with gastritis and 0.54(0.44–0.67)for patients after resection in cohort studies.CONCLUSION In the East Asian population with a high risk of GC,H.pylori eradication effectively reduced the risk of GC,irrespective of past history of previous cancer.

Success of susceptibility-guided eradication of Helicobacter pylori in a region with high secondary clarithromycin and levofloxacin resistance rates

BACKGROUND Resistance to clarithromycin(CLA)and levofloxacin(LFX)of Helicobacter pylori(H.pylori)is increasing in severity,and successful eradication is essential.Presently,the eradication success rate has greatly declined,leaving a large number of patients with previous treatment histories.AIM To investigate secondary resistance rates,explore risk factors for antibiotic resistance,and assess the efficacy of susceptibility-guided therapy.METHODS We recruited 154 subjects positive for Urea Breath Test who attended The First Affiliated Hospital of China Medical University between July 2022 and April 2023.Participants underwent a string test after an overnight fast.The gastric juice was obtained and transferred to vials containing storage solution.Subsequently,DNA extraction and the specific DNA amplification were performed using quantitative polymerase chain reaction(qPCR).Demographic information was also analyzed as part of the study.Based on these results,the participants were administered susceptibility-guided treatment.Efficacy was compared with that of the empiric treatment group.RESULTS A total of 132 individuals tested positive for the H.pylori ureA gene by qPCR technique.CLA resistance rate reached a high level of 82.6%(n=109),LFX resistance rate was 69.7%(n=92)and dual resistance was 62.1%(n=82).Gastric symptoms[odds ratio(OR)=2.782;95%confidence interval(95%CI):1.076-7.194;P=0.035]and rural residence(OR=5.152;95%CI:1.407-18.861;P=0.013)were independent risk factors for secondary resistance to CLA and LFX,respectively.A total of 102 and 100 individuals received susceptibility-guided therapies and empiric treatment,respectively.The antibiotic susceptibility-guided treatment and empiric treatment groups achieved successful eradication rates of 75.5%(77/102)and 59.0%(59/411)by the intention-to-treat(ITT)analysis and 90.6%(77/85)and 70.2%(59/84)by the per-protocol(PP)analysis,respectively.The eradication rates of these two treatment strategies were significantly different in both ITT(P=0.001)and PP(P=0.012)analyses.CONCLUSION H.pylori presented high secondary resistance rates to CLA and LFX.For patients with previous treatment failures,treatments should be guided by antibiotic susceptibility tests or regional antibiotic resistance profile.

Efficacy and safety of low-dose tetracycline,amoxicillin quadruple therapy in Helicobacter pylori infection:A retrospective single center study

BACKGROUND Helicobacter pylori(H.pylori)eradication rates have declined with the rise of antibiotic-resistant strains in recent years.Although highly effective with a low prevalence of resistance,standard dose tetracycline is associated with frequent adverse events.The efficacy and safety of low-dose tetracycline as part of tetra-cycline and amoxicillin-containing bismuth quadruple therapy are not well described.AIM To compare the efficacy and safety of low-dose compared to standard dose tetracycline with combined amoxicillin-containing bismuth quadruple therapy in patients with H.pylori infection.METHODS Consecutive patients with H.pylori infection receiving tetracycline,amoxicillin,proton pump inhibitor,and bismuth for 14 days at Sir Run Run Shaw Hospital(1/2022-6/2023)were evaluated.The low-dose tetracycline group received tetracycline 500 mg twice daily(bid)while the standard dose group received 750 mg bid or 500 mg three times daily(tid).Primary endpoints were H.pylori eradication rate and treatment-related adverse events.

Third-line and rescue therapy for refractory Helicobacter pylori infection: A systematic review

BACKGROUND Due to increasing resistance rates of Helicobacter pylori(H.pylori)to different antibiotics,failures in eradication therapies are becoming more frequent.Even though eradication criteria and treatment algorithms for first-line and second-line therapy against H.pylori infection are well-established,there is no clear recommendation for third-line and rescue therapy in refractory H.pylori infection.AIM To perform a systematic review evaluating the efficacy and safety of rescue therapies against refractory H.pylori infection.METHODS A systematic search of available rescue treatments for refractory H.pylori infection was conducted on the National Library of Medicine’s PubMed search platform based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Randomized or non-randomized clinical trials and observational studies evaluating the effectiveness of H.pylori infection rescue therapies were included.RESULTS Twenty-eight studies were included in the analysis of mean eradication rates as rescue therapy,and 21 of these were selected for analysis of mean eradication rate as third-line treatment.For rifabutin-,sitafloxacin-,levofloxacin-,or metronidazole-based triple-therapy as third-line treatment,mean eradication rates of 81.6%and 84.4%,79.4%and 81.5%,55.7%and 60.6%,and 62.0%and 63.0%were found in intention-to-treat(ITT)and per-protocol(PP)analysis,respectively.For third-line quadruple therapy,mean eradication rates of 69.2%and 72.1%were found for bismuth quadruple therapy(BQT),88.9%and 90.9%for bismuth quadruple therapy,three-in-one,Pylera®(BQT-Pylera),and 61.3%and 64.2%for non-BQT)in ITT and PP analysis,respectively.For rifabutin-,sitafloxacin-,levofloxacin-,or metronidazole-based triple therapy as rescue therapy,mean eradication rates of 75.4%and 78.8%,79.4 and 81.5%,55.7%and 60.6%,and 62.0%and 63.0%were found in ITT and PP analysis,respectively.For quadruple therapy as rescue treatment,mean eradication rates of 76.7%and 79.2%for BQT,84.9%and 87.8%for BQT-Pylera,and 61.3%and 64.2%for non-BQT were found in ITT and PP analysis,respectively.For susceptibility-guided therapy,mean eradication rates as third-line and rescue treatment were 75.0%in ITT and 79.2%in PP analysis.CONCLUSION We recommend sitafloxacin-based triple therapy containing vonoprazan in regions with low macrolide resistance profile.In regions with known resistance to macrolides or unavailability of bismuth,rifabutin-based triple therapy is recommended.

Safety and effectiveness of vonoprazan-based rescue therapy for Helicobacter pylori infection

BACKGROUND Vonoprazan(VPZ)-based regimens are an effective first-line therapy for Helicobacter pylori(H.pylori)infection.However,their value as a rescue therapy needs to be explored.AIM To assess a VPZ-based regimen as H.pylori rescue therapy.METHODS This prospective,single-center,clinical trial was conducted between January and August 2022.Patients with a history of H.pylori treatment failure were administered 20 mg VPZ twice daily,750 mg amoxicillin 3 times daily,and 250 mg Saccharomyces boulardii(S.boulardii)twice daily for 14 d(14-d VAS regimen).VPZ and S.boulardii were taken before meals,while amoxicillin was taken after meals.Within 3 d after the end of eradication therapy,all patients were asked to fill in a questionnaire to assess any adverse events they may have experienced.At least 4-6 wk after the end of eradication therapy,eradication success was assessed using a 13C-urea breath test,and factors associated with eradication success were explored.RESULTS Herein,103 patients were assessed,and 68 patients were finally included.All included patients had 1-3 previous eradication failures.The overall eradication rates calculated using intention-to-treat and per-protocol analyses were 92.6%(63/68)and 92.3%(60/65),respectively.The eradication rate did not differ with the number of treatment failures(P=0.433).The rates of clarithromycin,metronidazole,and levofloxacin resistance were 91.3%(21/23),100.0%(23/23),and 60.9%(14/23),respectively.There were no cases of resistance to tetracycline,amoxicillin,or furazolidone.In 60.9%(14/23)patients,the H.pylori isolate was resistant to all 3 antibiotics(clarithromycin,metronidazole,and levofloxacin);however,eradication was achieved in 92.9%(13/14)patients.All patients showed metronidazole resistance,and had an eradication rate of 91.3%(21/23).The eradication rate was higher among patients without anxiety(96.8%)than among patients with anxiety(60.0%,P=0.025).No severe adverse events occurred;most adverse events were mild and disappeared without intervention.Good compliance was seen in 95.6%(65/68)patients.Serological examination showed no significant changes in liver and kidney function.CONCLUSION VAS is a safe and effective rescue therapy,with an acceptable eradication rate(>90%),regardless of the number of prior treatment failures.Anxiety may be associated with eradication failure.

Effectiveness of Helicobacter pylori eradication in the treatment of early-stage gastric mucosa-associated lymphoid tissue lymphoma:An up-to-date meta-analysis

BACKGROUND Gastric mucosa-associated lymphoid tissue(MALT)lymphoma(GML)is usually a low-grade B-cell neoplasia strongly associated with Helicobacter pylori(H.pylori)-induced chronic gastritis.Clinical practice guidelines currently recommend H.pylori eradication as the preferred initial treatment for early-stage GML.To determine the practical effect of bacterial eradication as the sole initial therapy for early-stage GML,an updated analysis and review of available evidence is imperative.AIM To perform a meta-analysis to assess the rate of complete remission(CR)of H.pylori-positive early-stage GML following bacterial eradication.METHODS We performed independent,computer-assisted literature searches using the PubMed/MEDLINE,Embase,and Cochrane Central databases through September 2022.Prospective and retrospective observational studies evaluating the CR of early-stage GML following bacterial eradication in H.pylori-positive patients.The risk of bias was assessed using Joanna Briggs Institute(JBI)Critical Appraisal Tools.The pooled estimate of the complete histopathological remission rate and respective confidence intervals(95%CI)were calculated following the random-effects model.Heterogeneity and inconsistency were assessed using Cochran’s Q test and I2 statistic,and heterogeneity was defined as P<0.01 and I²>50%,respectively.Subgroup and meta-regression analyses were conducted to explore potential sources of heterogeneity.RESULTS The titles and abstracts of 1576 studies were screened;96 articles were retrieved and selected for full-text reading.Finally,61 studies were included in the proportional meta-analysis(P-MA).Forty-six were prospective and fifteen were retrospective uncontrolled,single-arm,observational studies.The overall risk of bias was low to moderate in all but a single report,with an average critical appraisal score across all studies of 79.02%.A total of 2936 H.pylori-positive early-stage GML patients,in whom H.pylori was successfully eradicated,were included in the analysis.The pooled CR of H.pylori-positive early-stage GML after bacterial eradication was 75.18%(95%CI:70.45%-79.91%).P-MA indicated the substantial heterogeneity in CR reported across studies(I2=92%;P<0.01).Meta-regression analysis identified statistically significant effect modifiers,including the proportion of patients with t(11;18)(q21;q21)-positive GML and the risk of bias in each study.CONCLUSION Comprehensive synthesis of available evidence suggests that H.pylori eradication is effective as the sole initial therapy for early-stage GML.Although the substantial heterogeneity observed across studies limits the interpretation of the pooled overall CR,the present study is a relevant to informing clinical practice.

Efficacy and safety of modified tetracycline dosing in a quadruple therapy for Helicobacter pylori:A retrospective single center study

BACKGROUND Although highly effective as a component of Helicobacter pylori(H.pylori)treatment regimen,tetracycline is associated with a high incidence of medicationrelated adverse events.Modified dosing of tetracycline as part of quadruple therapy may improve safety while providing comparable eradication rates.AIM To evaluate the efficacy and safety of modified dosing of tetracycline in patients receiving tetracycline and furazolidone-containing quadruple therapy in patients with H.pylori infection.METHODS Consecutive patients(10/2020-12/2021)who received tetracycline and furazolidone quadruple therapy for H.pylori infection at Sir Run Run Shaw Hospital were identified.All patients received tetracycline,furazolidone,proton pump inhibitor,and bismuth for 14 d as primary or rescue therapy.Modified tetracycline dose group received tetracycline 500 mg twice daily while standard group received 750 mg twice daily or 500 mg three times daily.RESULTS Three hundred and ninety-four patients[mean age=46.3±13.9,male=137(34.8%),and 309(78.4%)primary therapy]completed tetracycline and furazolidone quadruple therapy for H.pylori infection including those who received modified tetracycline dose in 157 and standard doses in 118(750 mg twice daily)and 119(500 mg three times daily).Eradication rates in the modified tetracycline dose group were 92.40%and in the standard groups,eradication rates were 93.20%for 750 mg twice daily group and 92.43%for 500 mg three times daily group,respectively,without statistical difference(P=0.959).The incidence of adverse events was lower in the modified tetracycline dose(15.3%vs 32.3%and 29.4%;P=0.002)compared to the standard dose group.CONCLUSION In a real-world experience,modified tetracycline dosing as part of tetracycline and furazolidone quadruple therapy for 14 d demonstrated high efficacy,comparable to standard tetracycline dose regimens,with a favorable safety profile.

Disease trends after Helicobacter pylori eradication based on Japanese nationwide claims and the health check-up database

BACKGROUND Helicobacter pylori(H.pylori)infection is a risk factor for many diseases,including peptic ulcer disease and gastric cancer.While H.pylori eradication therapy can prevent these diseases,potentially unfavorable effects of eradication therapy have also been reported in some diseases,such as gastroesophageal reflux disease(GERD),Barrett’s esophagus(BE),inflammatory bowel disease(IBD),allergic diseases,and metabolic diseases.Consequently,both positive and negative impacts should be considered when assessing the effects of H.pylori eradication therapy.AIM To compare the incidence of these diseases before and after H.pylori eradication and to comprehensively assess its effects.METHODS This retrospective cohort study used a Japanese nationwide health claims database(April 2009-March 2020),developed by the Japanese Ministry of Health,Labour and Welfare.The database contained almost all health insurance claims data issued in Japan,and specific health check-up data for individuals who took the check-ups.Descriptive statistics were used for the analyses.Patients who received primary eradication therapy were defined as those prescribed medication for H.pylori eradication.New diagnoses,defined as incidence of upper gastrointestinal diseases and IBD,and prevalence of allergic diseases were compared before and after eradication.The incidence and prevalence of each disease were also compared between the 3-year period before eradication(from the 4th to the 2nd year prior to the year of eradication)and the 3-year period after eradication(from the 1st to the 3rd year after the year of eradication)based on the age category and calendar year and month.Changes in body mass index and proportion of patients with metabolic syndrome(MS)were examined before and after eradication.RESULTS We identified 5219731 patients who received primary eradication therapy.The 65-69 years age group had the greatest number of patients in both sexes.There was no significant increase in the incidence of GERD after eradication when considering the effects of aging and reporting period.However,the incidence of BE was higher in the 3-year period after eradication than in the 3-year period before eradication for all age categories(0.02%-0.10%vs<0.01%-0.05%).The incidence of IBD and prevalence of allergic disease were also higher after eradication.In contrast,the incidence of gastric and duodenal ulcers and gastritis was reduced after eradication.In patients with at least one entry of health check-up data(1701111 patients),the percentage of patients with MS showed a slight increase following eradication(11.0%in the year of eradication and 12.2%after 5 years).CONCLUSION The results suggest that H.pylori eradication therapy reduces peptic ulcers and gastritis;however,it is associated with increased incidence of several other chronic diseases.

Low efficacy of levofloxacin-doxycycline-based third-line triple therapy for Helicobacter pylori eradication in Italy

AIM:To evaluate a levofloxacin-doxycycline-based triple therapy with or without a susceptibility culture test in non-responders to Helicobacter pylori(H.pylori) eradication.METHODS:A total of 142(99 women,43 men; mean 53.0 ± 12.7 years) non-responders to more than two H.pylori eradication therapies underwent susceptibility culture tests or were treated with a seven-day triple therapy consisting of esomeprazole,20 mg b.i.d.,levofloxacin,500 mg b.i.d.,and doxycycline,100 mg b.i.d.,randomly associated with(n = 71) or without(n = 71) Lactobacillus casei DG.H.pylori status was checked in all patients at enrollment and at least 8 wk after the end of therapy.Compliance and tolerability of regimens were also assessed.RESULTS:H.pylori eradication was achieved in < 50% of patients [per prototol(PP) = 49%; intention to treat(ITT) = 46%].Eradication rate was higher in patients administered probiotics than in those without(PP = 55% vs 43%; ITT = 54% vs 40%).Estimated primary resistance to levofloxacin was 18% and multiple resistance was 31%.Therapy was well tolerated,and side effects were generally mild,with only one patient experiencing severe effects.CONCLUSION:Third-line levofloxacin-doxycycline triple therapy had a low H.pylori eradication efficacy,though the success and tolerability of this treatment may be enhanced with probiotics.

Helicobacter pylori eradication: Sequential therapy and Lactobacillus reuteri supplementation

AIM:To evaluate the role of sequential therapy and Lactobacillus reuteri (L. reuteri ) supplementation, in the eradication treatment of Helicobacter pylori (H. pylori ). METHODS:H. pylori infection was diagnosed in 90 adult dyspeptic patients. Patients were excluded if previously treated for H. pylori infection or if they were taking a proton pump inhibitor (PPI), H2-receptor antagonist or antibiotics. Patients were assigned to receive one of the following therapies:(1) 7-d triple therapy (PPI plus clarithromycin and amoxicillin or metronidazole) plus L. reuteri supplementation dur- ing antibiotic treatment; (2) 7-d triple therapy plus L. reuteri supplementation after antibiotic treatment; (3) sequential regimen (5-d PPI plus amoxicillin therapy followed by a 5-d PPI, clarithromycin and tinidazole) plus L. reuteri supplementation during antibiotic treatment; and (4) sequential regimen plus L. reuteri supplementation after antibiotic treatment. Successful eradication therapy was defined as a negative urea breath test at least 4 wk following treatment. RESULTS:Ninety adult dyspeptic patients were en- rolled, and 83 (30 male, 53 female; mean age 57 ± 13 years) completed the study. Nineteen patients were administered a 7-d triple treatment:11 with L. reuteri supplementation during and 8 after therapy. Sixty-four patients were administered a sequential regimen:32 with L. reuteri supplementation during and 32 after therapy. The eradication rate was significantly higher in the sequential group compared with the 7-d triple regimen (88% vs 63%, P = 0.01). No difference was found between two types of PPI. No difference in erad- ication rates was observed between patients submitted to L. reuteri supplementation during or after antibiotic treatment. Compliance with therapy was excellent in all patients. No difference in adverse effects was observed between the different antibiotic treatments and between patients submitted to L. reuteri supplementation during and after antibiotic treatment. There was a low incidence of adverse effects in all groups of patients with sequential therapy, probably due to the presence of the L. reuteri supplementation. CONCLUSION:The sequential treatment regimen achieved a significantly higher eradication rate of H. pylori compared with standard 7-d regimen. L. reuteri supplementation could reduce the frequency and the intensity of antibiotic-associated side-effects.

Tailored eradication strategy vs concomitant therapy for Helicobacter pylori eradication treatment in Korean patients

BACKGROUND Antibiotic resistance to Helicobacter pylori(H.pylori)infection,which ultimately results in eradication failure,has been an emerging issue in the clinical field.Recently,to overcome this problem,an antibiotic sensitivity-based tailored therapy(TT)for H.pylori infection has received attention.AIM To investigate the efficacy and safety profiles of TT for H.pylori infection treatment compared to a non-bismuth quadruple therapy,concomitant therapy(CT)regimen.METHODS We included patients(>18 years)with an H.pylori infection and without a history of Helicobacter eradication who visited the Gil Medical Center between March 2016 and October 2020.After being randomly assigned to either the TT or CT treatment group in 1 to 1 manner,patient compliance,eradication success rate(ESR),and patient-reported side effects profiles were assessed and compared between the two groups.H.pylori infection was diagnosed using a rapid urease test,Giemsa stain,or dual priming oligonucleotide polymerase chain reaction(DPO-PCR).Tailored eradication strategy based through the presence of a 23S ribosomal RNA point mutation.For the TT group,a DPO-PCR test,which detected A2142G and/or A2143G point mutations,and a clarithromycin resistance test were performed.Patients in the clarithromycin-resistant group were treated with a bismuth-containing quadruple combination therapy,while those with sensitive results were treated with the standard triple regimen.RESULTS Of the 217 patients with a treatment naive H.pylori infection,110 patients[mean age:58.66±13.03,men,n=55(50%)]were treated with TT,and 107 patients[mean age:56.67±10.88,men,n=52(48.60%)]were treated with CT.The compliance(TT vs CT,100%vs 98.13%,P=0.30),and follow-up loss rates(8.18%vs 9.35%,P=0.95)were not significantly different between the groups.The ESR after treatment was also not statistically different between the groups(TT vs CT,82.73%vs 82.24%,P=0.95).However,the treatment-related and patient-reported side effects were significantly lower in the TT group than in the CT group(22.77%vs 50.52%,P<0.001).CONCLUSION The DPO-based TT regimen shows promising results in efficacy and safety profiles as a first-line Helicobacter eradication regimen in Korea,especially when physicians are confronted with increased antibiotic resistance rates.