Effectiveness And Adverse Reactions Of Different Helicobacter Pylori Eradication Regimens And Their Influence Factors

Background and aims:Helicobacter pylori（Hp）infection has been shown to be associated with a variety of numerous diseases in the gastrointestinal tract and outside the gastrointestinal tract,and Hp eradication is extremely important for the treatment and prevention of Hp-related diseases.Under the background of increasing resistance rates of Hp to nitroimidazole,macrolide,and quinolone antibiotics,the eradication rate of Hp decreased gradually,so domestic and foreign consensuses have successively recommended a variety of eradication regimens whose efficacy and safety have been confirmed by strict randomized controlled trails（RCT）.However,most objects of RCT come from the ideal world population,and the results are high in internal validity but poor extrapolation.The objects of real-world study（RWS）come from the clinical real-world population,and the results have good external authenticity.Therefore,based on real-world data,this study will analyze the effectiveness and adverse reactions of different eradication regimens in actual clinical practice,and explore influence factors of Hp eradication failure and side effects,so as to provide a theoretical basis for formulating an efficient and safe treatment scheme for Hp eradication.Methods:1.The objects of study:From December 2019 to February 2022,patients who were confirmed to infected Hp by ¹³C-UBT DOB value>6‰or ¹⁴C-UBT DPM value>critical value+50%critical value or rapid urease test≥（++）（to rule out near the critical value of false positives）or histopathology or bacterial culture,and received eradication treatment in Hp specialist clinics and partial general clinics of the First Affiliated Hospital of Nanchang University,and met both inclusion and exclusion criteria were included in this study,including:（1）patients who received Hp eradication therapy in our department（prospective study）;（2）patients who had undergone Hp eradication therapy in other hospitals and visit our department within1 month after completion of eradication therapy（retrospective study）.2.Eradication regimens:bismuth quadruple regimens:PBAF,PBFTc,PBAC,PBAL,PBAM,PBATc,PBFC,PBCTi（P:acid suppressant,B:bismuth,A:amoxicillin,F:furazolidone,Tc:tetracycline,C:clarithromycin,L:levofloxacin,M:metronidazole,Ti:tinidazole）;triple therapy（acid suppressant+two antibiotics）;dual therapy（acid suppressant+amoxicillin 1g bid/tid）;others（bismuth quadruple therapy that not belong to the above antibiotic combination,non-bismuth quadruple therapy and other irregular regimens）,the duration of all regimens is 10 or 14 days.3.Research process:Outpatients enrolled in Hp eradication were informed and filled out questionnaires to record their demographics and clinical baseline data.Within±2days after completion of Hp eradication,changes in gastrointestinal symptoms,adverse events and compliance during treatment were obtained via clinic or telephone return visit.The patients had undergone Hp eradication therapy in other hospitals,the above indicators were recorded when they visited our department within 1 month after completion of therapy.At least 4 weeks after completion of therapy,Hp eradication was assessed by ¹³C-UBT or ¹⁴C-UBT or histopathology,changes in gastrointestinal symptoms and the results of detection of Hp were followed up via outpatient or telephone.6 months after eradication,Hp-negative patients were re-examined the status of Hp infection.4.Statistical analysis:SPSS 26.0 software was used for all statistical analyses.Continuous variables were expressed as mean±standard deviation（Mean±SD）.Categorical variables were expressed as frequency（n）and rate（%）,the inter-group comparison was based on the Pearson chi-square test,the adjusted chi-square test or Fisher’s exact test,and the multiple rates are compared by the Bonferroni method.Multivariate analysis using binary logistic regression was applied to calculate odd ratio（OR）and 95%confidence interval（CI）of influence factors.All results were considered statistically significant when P（27）0.05 by bilateral test statistics.Results:1.Enrollment situation:A total of 2504 outpatients who underwent Hp eradication therapy were included,and 2237 patients（89.3%）completed the follow-up of adverse reactions,which is a follow-up dataset of adverse events.1665patients（75.8%）completed the re-examination of Hp 4 weeks after eradication,267patients confirmed by UBT detection value within the critical value±50%critical value and 5 patients received anti-Hp treatment again without re-examination of Hp infection were excluded.Finally,1393 patients with complete follow-up who met the inclusion criteria and Hp eradication criteria were included.2.Eradication rate and its influence factors:Among the 1393 patients in the complete follow-up dataset,the overall eradication rates were 85.8%by modified intention-to-treat（m ITT）analysis and 88.4%by per-protocol（PP）analysis.From high to low,m ITT eradication rates of different eradication regimens were PBFTc（96.2%）,high-efficiency and high-dose dual therapy（94.1%）,PBATc（88.2%）,PBAF（87.4%）,PBAM（81.8%）,PBAL（69.0%）,PBAC（68.3%）,other therapy（61.4%）,PBFC（57.1%）,triple therapy（41.7%）,PBCTi（29.2%）.Multivariate logistic regression analysis suggested that female,14-day duration,high-efficiency and high-dose acid suppressants were protective factors for Hp eradication efficacy.Previous history of Hp eradication,colloidal bismuth tartrate,and poor compliance were risk factors for Hp eradication failure.Compared with PBAF regimen,PBFTc regimen had a lower risk of eradication failure,and PBAC,PBAL,PBFC,PBCTi,triple therapy,and other therapy had a higher risk of eradication failure.3.Incidence of adverse reactions and its influence factors:Among the 2237patients in the follow-up dataset of adverse reactions,18.2%（407 patients）experienced at least one adverse event.Nausea/vomiting（5.4%）,headache/dizziness（3.4%）,abdominal pain/bloating（3.0%）,dry/bitter taste in mouth（2.1%）and diarrhea（1.8%）were the most frequent adverse events.The majority of adverse reactions were mild（77.8%）,3.6%（80 patients）discontinued treatment due to adverse reactions,and the overall compliance rate was 96.0%.The average time of onset of adverse reactions was 3.6±2.7 days,lasted for 7.4±4.0 days,and most of them disappeared gradually after drug withdrawal.From high to low,the incidences of adverse reactions of different eradication regimens were PBFC（53.3%）,other therapy（34.4%）,triple therapy（32.7%）,PBAM（32.3%）,PBCTi（29.6%）,PBAC（21.4%）,PBFTc（19.4%）,PBAF（14.3%）,dual therapy（12.0%）,PBATc（7.7%）,PBAL（2.7%）.Multivariate logistic regression analysis suggested that female was a risk factor for adverse reactions.Poor compliance was associated with adverse reactions.Compared with PBAF regimen,PBFTc,PBAC,PBAM,PBFC,triple therapy,and other therapy had higher risks of adverse reactions.4.Half-year recurrence rate:The follow-up rate of Hp re-examination after half a year was 29.1%（280/961）,4 patients showed positive results,and the half-year recurrence rate was 1.43%（4/280）.Conclusions:1.Bismuth quadruple regimens combined with two antibiotics with low resistance rates and high-efficiency and high-dose dual therapy can achieve higher Hp eradication rates.2.Gender,number of previous Hp eradication,eradication regimen,duration of treatment,dose of acid suppressants,type of bismuth and compliance were independent influence factors of Hp eradication efficacy.3.The incidence of adverse reactions during Hp eradication was 18.2%,and the symptoms were usually mild and disappeared after drug withdrawal.Gender,and eradication regimen were independent influence factors of adverse reactions.