Joint ESPGHAN/NASPGHAN Guidelines for the …

1 Copyright ESPGHAL and naspghan . All rights ESPGHAN/NASPGHAN Guidelines for theManagement ofHelicobacter pyloriin children andAdolescents (Update 2016) Nicola L. Jones,ySibylle Koletzko,zKaren Goodman, Patrick Bontems,jjSamy Cadranel, Thomas Casswall,#Steve Czinn, Benjamin D. Gold,yyJeannette Guarner,zzYoram Elitsur, Matjaz Homan,jjjjNicolas Kalach, Michal Kori,##Armando Madrazo, Francis Megraud,yyyAlexandra Papadopoulou, andzzzMarion Rowland, on behalf of espghan , NASPGHANABSTRACTB ackground:Because of the changing epidemiology ofHelicobacter pyloriinfection and low efficacy of currently recommended therapies, an update ofthe European Society for Paediatric Gastroenterology Hepatology andNutrition/North American Society for Pediatric Gastroenterology, Hepatol-ogy and Nutrition recommendations for the diagnosis and management ofHpyloriinfection in children and adolescents is :A systematic review of the literature (time period: 2009 2014) wasperformed.

2 Representatives of both societies evaluated the quality of evidenceusing GRADE (Grading of Recommendation Assessment, Development, andEvaluation) to formulate recommendations, which were voted upon andfinalized using a Delphi process and face-to-face :The consensus group recommended that invasive diagnostic testing forHpyloribe performed only when treatment willbe offered if tests are positive. Toreach the aim of a 90% eradication rate with initial therapy, antibiotics should betailored according to susceptibility testing. Therapy should be administered for14 days, emphasizing strict regimensshouldberestrictedtochildreninfe cted with susceptible strains. Whenantibiotic susceptibility profiles are not known, high-dose triple therapy withproton pump inhibitor, amoxicillin, and metronidazole for 14 days or bismuth-based quadruple therapy is recommended. Success of therapy should bemonitored after 4 to 8 weeks by reliable noninvasive :The primary goal of clinical investigation is to identify thecause of upper gastrointestinal symptoms rather thanH , we recommend against a test and treat strategy.

3 Decreasingeradication rates with previously recommended treatments call for changesto first-line therapies and broader availability of culture or molecular-basedtesting to tailor treatment to the individual :adolescents, antibiotic susceptibility,13C-urea breath test, children , eradication,Helicobacter pylori, triple therapy(JPGN2017;64: 991 1003)Helicobacter pyloriinfection is acquired in childhood andremains an important cause of peptic ulcer disease (PUD)and gastric cancer (1). In comparison with adults, children andadolescents, however, infrequently develop these complications ofinfection. FurthermoreH pyloriinfection in early childhood may beassociated with immunologic benefits later in life (2).The updated recommendations were extensively discussed inthe light of decreasing efficacy ofH pylorieradication therapy inchildren and the rising prevalence of antibiotic-resistant pyloriinfection is always associated with microscopicgastric inflammation, the overwhelming majority ofH pylori infected children are asymptomatic.

4 Studies in children do notsupport a role forH pyloriinfection in functional disorders suchas recurrent abdominal pain (3). Therefore in children the decisionto investigate and treat the infection should be supported by a clearbenefit for the individual is renewed hope in the potential for primary preventionof infection based on the results of a recent vaccine study in Chinesechildren (4). Optimization of the vaccine strategy is, however,required to ensure long-lasting protection. Furthermore, additionalstudies demonstrating efficacy in different geographic regions arealso needed before this vaccination strategy can be adopted inclinical recommended goal forH pyloritreatment is an eradica-tion rate of at least 90% to avoid further investigations andantibiotic use (5). First-line therapies recommended in previousguidelines have unacceptable treatment failures rates (6). Thus,based on the declining prevalence of the infection in somecountries, and the ineffectiveness of previously recommendedfirst-line eradication therapies, European Society for PaediatricGastroenterology Hepatology and Nutrition ( espghan ) andNorth American Society for Pediatric Gastroenterology, Hepatol-ogy and Nutrition ( naspghan ) determined that updatedReceived July 4, 2016; accepted March 10, the Division of Gastroenterology, Hepatology and Nutrition, CellBiology Program, Sickkids Toronto, Departments of Paediatrics andPhysiology, University of Toronto, Toronto, Canada, theyDivision ofGastroenterology and Hepatology, Dr.

5 Von Hauner children s Hospital,Ludwig Maximilians University, Munich, Germany, thezDepartment ofMedicine and School of Public Health, Centre of Excellence for Gastro-intestinal Inflammation and Immunity Research, University of Alberta,Edmonton, Alberta, Canada, the Paediatric Gastroenterology Depart-ment, Ho pital Universitaire des Enfants Reine Fabiola, thejjDepartmentof Paediatric Gastroenterology, Queen Fabiola University children sHospital, Universite Libre de Bruxelles, Brussels, Belgium, the Pediatric Gastroenterology, Hepatology, and Nutrition, CLINTEC,Karolinska Institutet and Karolinska University Hospital, Stockholm,Sweden, the#Department of Pediatrics, University of Maryland Schoolof Medicine, Baltimore, MD, the children s Center for DigestiveHealthcare, LLC, Gi Care for Kids, LLC, children s Healthcare ofAtlanta, theyyDepartment of Pathology and Laboratory Medicine, EmoryUniversity, Atlanta, GA, thezzDepartment of Pediatrics, Gastroenterol-ogy Division, Marshall University School of Medicine, Huntington, WV,the Faculty of Medicine, Department of Gastroenterology, Hepatologyand Nutrition, University children s Hospital Ljubljana, Ljubljana, Slo-venia, thejjjjSaint Antoine Pediatric Clinic, Saint Vincent de PaulHospital, Groupement de l Institut Catholique de Lille (GH-ICL)

6 , Catho-lic University, Lille, France, the Kaplan Medical Center, HadassahMedical School, Hebrew University, Jerusalem, Israel, the##PediatricGastroenterology Division, Hospital de Pediatr a, Centro Medico Nacio-nal Siglo XXI, Mexico City, Mexico, the Laboratoire deBacte riologie, Universite de Bordeaux, Bordeaux, France, theyyyDivision of Gastroenterology, Hepatology and Nutrition, First Depart-ment of Pediatrics, University of Athens, children s Hospital , Athens, Greece, and thezzzSchool of Medicine, UniversityCollege Dublin, Dublin, Volume 64, Number 6, June 2017991 Copyright ESPGHAL and naspghan . All rights forH pyloriinfection in children and adolescentswere Guidelines apply only to pediatric patients, defined aschildren and adolescents below 18 years of age. Recommendationsfor children and adolescents may differ from recent Guidelines foradults because of a different risk-benefit ratio depending on ageand the fact that some antibiotics are not released or licensed forthe pediatric population.

7 The guidance in this document does notindicate an exclusive course of treatment or serve as a standardof medical care. Variations, taking into account individual andnational circumstances, may be appropriate. This applies parti-cularly to developing countries with highH pyloriinfection ratesin children and adolescents and with limited resources forhealth and PurposeJoint ESPGHAN/NASPGHAN Guidelines were developed forthe management ofH pyloriinfection in children and adolescents in2009 and published in 2011 (6). Based on new clinical knowledge andin particular, increasing challenges with eradication therapy, NASP-GHAN and espghan agreed to review the current literature toprovide updated Guidelines for the management ofH pyloriinfectionin the pediatric population in North America and ReviewA systematic literature search using PubMed, MEDLINE,EMBASE, Cochrane Library, and Scopus databases between Octo-ber 1, 2009 to September 2014 using the following MESH terms(( adolescent [Mesh] OR Child [Mesh] OR Infant [Mesh]OR Minors [Mesh] OR Pediatrics [Mesh]) AND ( Helicobac-ter pylori [Mesh] OR Helicobacter Infections [Mesh])) ( ).

8 Studies were restricted to humans and conference abstracts and non-English literature were , Grading of Evidence, and ConsensusProcessThe consensus group consisted of an international groupofexpertsincludingpediatricgastroen terologists,clinicalTABLE 1. Guideline recommendationsSynopsis of recommendations1. We recommend that the primary goal of clinical investigation of gastrointestinal symptoms should be to determine the underlying cause of the symptoms andnot solely the presence ofH We recommend that during endoscopy additional biopsies for RUT and culture should only be taken if treatment is likely to be offered if infection We suggest that ifH pyloriinfection is an incidental finding at endoscopy, treatment may be considered after careful discussion of the risks and benefits ofHpyloritreatment with the We recommend against a test and treat strategy forH pyloriinfection in We recommend that testing forH pyloribe performed in children with gastric or duodenal ulcers.

9 IfH pyloriinfection is identified then treatment should beadvised and eradication be We recommend against diagnostic testing forH pyloriinfection in children with functional abdominal We recommend against diagnostic testing forH pyloriinfection as part of the initial investigation in children with iron deficiency We suggest that in children with refractory IDA in which other causes have been ruled out, testing forH pyloriduring upper endoscopy may be We suggest that noninvasive diagnostic testing forH pyloriinfection may be considered when investigating causes of chronic immune thrombocytopenicpurpura (ITP).7. We recommend against diagnostic testing forH pyloriinfection when investigating causes of short We recommend that before testing forH pylori,waiting at least 2 weeks after stopping proton pump inhibitor (PPI) and 4 weeks after stopping We recommend that the diagnosis ofH pyloriinfection should be based on either (a) histopathology (H pylori positive gastritis) plus at least 1 otherpositive biopsy-based test or (b) positive We recommend that for the diagnosis ofH pyloriinfection at upper gastrointestinal endoscopy, at least 6 gastric biopsies be We recommend against using antibody-based tests (IgG, IgA) forH pyloriin serum, whole blood, urine, and saliva in the clinical We recommend that antimicrobial sensitivity be obtained for the infectingH pyloristrain (s)

10 , and eradication therapy tailored We recommend that the effectiveness of first-line therapy be evaluated in national/regional We recommend that the physician explain to the patient/family the importance of adherence to the anti H pyloritherapy to enhance successful We recommend first-line therapy forH pyloriinfection as listed in Table We recommend that the outcome of anti H pyloritherapy be assessed at least 4 weeks after completion of therapy using one of the following tests.(a) The13C-urea breath (13C-UBT) test or (b) a 2-step monoclonal stool antigen We recommend that whenH pyloritreatment fails, rescue therapy should be individualized considering antibiotic susceptibility, the age of the child, andavailable antimicrobial iron deficiency anemia; RUT rapid urease correspondence and reprint requests to Dr Sibylle Koletzko, MD,PhD, Hauner children s Hospital, Munich Medical Centre, LudwigMaximilians University, Lindwurmstr. 4, 80337 Munich, Germany(e-mail: article has been developed as a Journal CME Activity byNASPGHAN.)