Article Text

Original research
European Registry on Helicobacter pylori management (Hp-EuReg): patterns and trends in first-line empirical eradication prescription and outcomes of 5 years and 21 533 patients
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  1. Olga P Nyssen1,
  2. Dmitry Bordin2,3,
  3. Bojan Tepes4,
  4. Ángeles Pérez-Aisa5,
  5. Dino Vaira6,
  6. Maria Caldas1,
  7. Luis Bujanda7,
  8. Manuel Castro-Fernandez8,
  9. Frode Lerang9,
  10. Marcis Leja10,
  11. Luís Rodrigo11,
  12. Theodore Rokkas12,
  13. Limas Kupcinskas13,
  14. Jorge Pérez-Lasala14,
  15. Laimas Jonaitis13,
  16. Oleg Shvets15,
  17. Antonio Gasbarrini16,
  18. Halis Simsek17,
  19. Anthony T R Axon18,
  20. György Buzás19,
  21. Jose Carlos Machado20,
  22. Yaron Niv21,
  23. Lyudmila Boyanova22,
  24. Adrian Goldis23,
  25. Vincent Lamy24,
  26. Ante Tonkic25,
  27. Krzysztof Przytulski26,
  28. Christoph Beglinger27,
  29. Marino Venerito28,
  30. Peter Bytzer29,
  31. Lisette Capelle30,
  32. Tomica Milosavljević31,
  33. Vladimir Milivojevic31,
  34. Lea Veijola32,
  35. Javier Molina-Infante33,
  36. Liudmila Vologzhanina34,
  37. Galina Fadeenko35,
  38. Ines Ariño36,
  39. Giulia Fiorini6,
  40. Ana Garre1,
  41. Jesús Garrido37,
  42. Cristina F Pérez38,
  43. Ignasi Puig39,
  44. Frederic Heluwaert40,
  45. Francis Megraud41,
  46. Colm O'Morain42,
  47. Javier P Gisbert1
  48. On behalf of the Hp-EuReg Investigators
    1. 1 Gastroenterolgy Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), Madrid, Spain
    2. 2 Department of Pancreatic, Biliary and Upper Digestive Tract Disorders, AS Loginov Moscow Clinical Scientific Center, Moscow, Russian Federation
    3. 3 A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Russian Federation
    4. 4 Gastroenterology, AM DC Rogaska, Rogaska Slatina, Slovenia
    5. 5 Gastroenterology, Agencia Sanitaria Costa del Sol, Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Marbella, Spain
    6. 6 Department of of Surgical and Medical Sciences, University of Bologna, Bologna, Italy
    7. 7 Gastroenterology, Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco (UPV/EHU), CIBEREHD, San Sebastian, Spain
    8. 8 Gastroenterology, Hospital de Valme, CIBEREHD, Sevilla, Spain
    9. 9 Gastroenterololgy, Østfold Hospital Trust, Grålum, Norway
    10. 10 Digestive Diseases Centre GASTRO, Institute of Clinical and Preventive Medicine & Faculty of Medicine, University of Latvia, Riga, Latvia
    11. 11 Gastroenterology, Hospital Universitario Central de Asturias, Oviedo, Spain
    12. 12 Gastroenterology, Henry Dunant Hospital, Athens, Greece
    13. 13 Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania
    14. 14 Gastroenterology, HM Sanchinarro, Madrid, Spain
    15. 15 Internal Medicine, National Medical University named after O.O.Bogomolets, Kyiv, Ukraine
    16. 16 Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
    17. 17 Internal Medicine/Gastroenterology, Hacettepe University Faculty of Medicine, Ankara, Turkey
    18. 18 Gastroenterology, Leeds General Infirmary, Leeds, UK
    19. 19 Gastroenterology, Ferencváros Health Centre, Budapest, Hungary
    20. 20 i3S - Instituto de Investigação e Inovação em Saúde. Medical Faculty of Porto. Universidade do Porto, Porto, Portugal
    21. 21 Gastroenterology, Rabin Medical Center, Tel Aviv University, Petah Tikva, Israel
    22. 22 Medical Microbiology, Medical University of Sofia, Sofia, Bulgaria
    23. 23 Gastroenterology, Timisoara Hospital, Timisoara, Romania
    24. 24 Gastroenterology, Hepatology & Nutrition, CHU de Charleroi, Charleroi, Belgium
    25. 25 Gastroenterology, University Hospital of Split, University of Split, Split, Croatia
    26. 26 Gastroenterology, Medical Centre for Postgraduate Education, Warsaw, Poland
    27. 27 Gastroenterology, University Hospital Basel, Basel, Switzerland
    28. 28 Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany
    29. 29 Clinical Medicine, Zealand University Hospital, Copenhagen University, Copenhagen, Denmark
    30. 30 Gastroenterology and Hepatology, Meander Medical Center, Amersfoort, Netherlands
    31. 31 Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia and School of Medicine, University of Belgrade, Belgrade, Serbia
    32. 32 Internal Medicine, Herttoniemi Hospital, Helsinki, Finland
    33. 33 Gastroenterology, Hospital San Pedro de Alcántara, CIBEREHD, Cáceres, Spain
    34. 34 Gastroenterology, Gastrocentr, Perm, Russian Federation
    35. 35 Gastroenterology, Digestive Ukrainian Academy of Medical Sciences, Kyiv, Ukraine
    36. 36 Gastroenterology, Hospital Clinico Universitario Lozano Blesa, CIBEREHD, Zaragoza, Spain
    37. 37 Departmento de Psicología Social y Metodología, Facultad de Psicología, Universidad Autónoma de Madrid, Madrid, Spain
    38. 38 Servicio de Medicina Preventiva, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain
    39. 39 Gastroenterology, Althaia Xarxa Assistencial Universitària de Manresa and Universitat de Vic-Universitat Central de Catalunya (UVicUCC), Manresa, Spain
    40. 40 Centre Hospitalier Annecy Genevois, Pringy, France
    41. 41 Laboratoire de Bactétiologie, Hôpital Pellegrin, Bordeaux, France
    42. 42 Gastroenterology, Trinity College Dublin, Dublin, Ireland
    1. Correspondence to Dr Javier P Gisbert, Gastroenterology Department, Hospital Universitario de La Princesa, Madrid, Spain; javier.p.gisbert{at}gmail.com

    Abstract

    Objective The best approach for Helicobacter pylori management remains unclear. An audit process is essential to ensure clinical practice is aligned with best standards of care.

    Design International multicentre prospective non-interventional registry starting in 2013 aimed to evaluate the decisions and outcomes in H. pylori management by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables included demographics, previous eradication attempts, prescribed treatment, adverse events and outcomes. Data monitoring was performed to ensure data quality. Time-trend and geographical analyses were performed.

    Results 30 394 patients from 27 European countries were evaluated and 21 533 (78%) first-line empirical H. pylori treatments were included for analysis. Pretreatment resistance rates were 23% to clarithromycin, 32% to metronidazole and 13% to both. Triple therapy with amoxicillin and clarithromycin was most commonly prescribed (39%), achieving 81.5% modified intention-to-treat eradication rate. Over 90% eradication was obtained only with 10-day bismuth quadruple or 14-day concomitant treatments. Longer treatment duration, higher acid inhibition and compliance were associated with higher eradication rates. Time-trend analysis showed a region-dependent shift in prescriptions including abandoning triple therapies, using higher acid-inhibition and longer treatments, which was associated with an overall effectiveness increase (84%–90%).

    Conclusion Management of H. pylori infection by European gastroenterologists is heterogeneous, suboptimal and discrepant with current recommendations. Only quadruple therapies lasting at least 10 days are able to achieve over 90% eradication rates. European recommendations are being slowly and heterogeneously incorporated into routine clinical practice, which was associated with a corresponding increase in effectiveness.

    • helicobacter pylori
    • helicobacter pylori - treatment

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    Footnotes

    • Correction notice This article has been corrected since it published Online First. The second author's name has been corrected.

    • Collaborators Jen Hinojosa (Agencia Sanitaria Costa del Sol Marbella Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Inmaculada Santaella (Agencia Sanitaria Costa del Sol Marbella Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Nuria Fernandez Moreno (Agencia Sanitaria Costa del Sol Marbella Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Ilaria Maria Saracino (University of Bologna Italy Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Horacio Alonso Galán (Hospital de Donisti San Sebastian Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Almudena Durán (Hospital de la Princesa Madrid Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Jennifer Fernandez Pacheco (Hospital de la Princesa Madrid Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Miroslav Vujasinovic (Slovenj Gradec General Hospital Slovenj Gradec Slovenia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Rinaldo Pellicano Molinette (Hospital Turin Italy Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Zdenko Kikec (General Hospital Slovenj Gradec Slovenj Gradec Slovenia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Pedro-Luis Gonzalez Cordero (Hospital San Pedro de Alcantara Caceres Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Maia Donday (Hospital de la Princesa, CIBERehd, Instituto de Salud Carlos III Madrid Spain Monitored and interpreted the data, critically reviewed and approved the final manuscript); Angel Lanas (Hospital Clinico Universitario Lozano Blesa Zaragoza Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Polona Lampic (Diagnosticni center Bled Bled Slovenia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Vid Leban (Diagnosticni center Bled Bled Slovenia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Aleksander Gruncic Krajnc (Diagnosticni center Bled d.o.o. Bled Slovenia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Natasa Brglez Jurecic (Diagnosticni center Bled d.o.o. Bled Slovenia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Galyna Dmytrivna Fadieienko (Ukrainian Academy of Medical Sciences Kharkiv Ukrania Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Lorena Lee (Instituto Fundación Teófilo Hernando Madrid Spain Monitored and interpreted the data, critically reviewed and approved the final manuscript); Irene V Barbado (Instituto Fundación Teófilo Hernando Madrid Spain Monitor and interpret the data, critically reviewed and approved the final manuscript); Alfredo José Lucendo (Hospital General de Tomelloso Tomelloso Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Jesus Barrio RIo Hortega (Hospital Valladolid Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Tatiana Alekseevna Ilchishina (SM-clinic Saint-Petersburg Russia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Irina Voynovan (Moscow Scientific Clinical Center Moscow Russia Acquired tdata, critically reviewed the manuscript draft and approved the submitted manuscript); Luis Ignacio Fernández-Salazar (Hospital Clínico Universitario Valladolid Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Jose María Huguet (Hospital General Universitario de Valencia Valencia Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Pilar Canelles (Hospital General Universitario de Valencia Valencia Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Aiman Silkanovna Sarsenbaeva (Gastroenterological center Chelyabinsk Russia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Ines Modolell Consorci (Sanitari Terrassa Terrassa Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Pedro Almela (Hospital General Universitario de Castellon Castellon Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Marina Roldán Lafuente (Hospital General Universitario de Castellón Castellón de la Plana Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Josep Maria Botargues (Hospital Universitari de Bellvitge L'Hospitalet de Llobregat Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Miguel Areia (Portuguese Oncology Institute Coimbra Portugal Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Luís Elvas (Portuguese Oncology Institute Coimbra Portugal Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Susana Isabel Alves (Portuguese Oncology Institute Coimbra Portugal Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Daniel Brito (Portuguese Oncology Institute Coimbra Portugal Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Ana Teresa Cadime (Portuguese Oncology Institute Coimbra Portugal Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Sandra Lúcia Madeira Saraiva (Oncologycal Hospital of Coimbra Coimbra Portugal Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Charalampos Tzathas (Tzaneio General Hospital Pireaus Greece Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Vassiliki Ntouli (Tzaneio General Hospital Pireaus Greece Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Alicia C Marin (Hospital de la Princesa, CIBERehd, Instituto de Salud Carlos III Madrid Spain Monitore and interpretd the data, critically reviewed the manuscript draft and approved the submitted manuscript); Cem Simsek (Hacettepe University Ankara Turkey Acquired data and approved the submitted manuscript); Gerardo Nardone University Federico II Naples Italy Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Alba Rocco (University Federico II Naples Italy Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Juan Antonio Ortuño (Hospital Universitari i Politècnic La Fe Valencia Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Tommaso Di Maira (University Hospital La Fe Valencia Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Sotirios D Georgopoulos (Athens Medical Center, Paleo Faliron General Hospital Athens Greece Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Stephan Brackmann (Lovisenberg Diakonale Hospital Oslo Norway Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); 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Sinead M Smith (Trinity College Dublin Dublin Ireland Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Denise Elizabeth Brennan (Trinity College Dublin Dublin Ireland Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Marina Fedorovna Osipenko (Novosibirsk State Medical University Novosibirsk Russia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Cristobal de la Coba (Hospital de Cabueñes Gijon Spain Acquired data, critically reviewed the manuscripts draft and approved the submitted manuscript); Pilar Varela (Hospital de Cabueñes Gijon Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Maria Anatolyevna Livzan (Omsk state medical academy Omsk Russia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Oleg V Zaytsev (First Clinical Medical Center Kovrov Russia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); 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Patric Mosler (Hospital of Chur Chur Switzerland Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Zaza Beniashvili (Rabin Medical Center, Hospital Ha Sharon Petah Tikva Israel Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Doron Boltin (Rabin Medical Center, Beilinson Campus Petah Tikva Israel Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Hubert Louis (Hôpital Erasme Brussels Belgium Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Ramon Pajares (Hospital Universitario Infanta Sofía San Sebastian de los Reyes Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Natalia Valerievna Zakharova (North-western State Medical University named after I.I.Mechnikov St. Petersburg Russia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Natalia Nikolaevna Dekhnich (Institute of Antimicrobial Chemotherapy Smolensk Russia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Victor Asparuhov Kamburov (Lyulin Hospital Sofia Bulgaria Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Maria Pina Dore (Clinica Medica, Dipartimento di Scienze Mediche, Chirurgiche e Sperimentali, Università di Sassari Sassari Italy Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Lorena Sancho (Del val Hospital Rey Juan Carlos Madrid Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Noelia Alcaide (Hospital Clínico Universitario Valladolid Spain Acquired the data, critically reviewed the manuscript draft and approved the submitted manuscript); Oscar Núñez (Hospital Universitario Sanitas La Moraleja Madrid Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Katrine Dvergsnes Sørlandet (Sykehus HF Kristiansand Norway Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Peter Malfertheiner (Otto-von-Guericke University Hospital Magdeburg Germany Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Ana Campillo (Hospital Reina Sofia Tudela Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Miguel Fernandez-Bermejo (Clinica San Francisco Caceres Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Manuel Domínguez-Cajal (Hospital San Jorge Huesca Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); José Luis Domínguez Jiménez (Alto Guadalquivir Hospital Andújar Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Alicia Algaba (Hospital Universitario de Fuenlabrada Madrid Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Fernando Bermejo (Hospital Universitario de Fuenlabrada Madrid Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Borislav Vladimirov (University hospotal Queen Ioanna-Isul Sofia Bulgaria Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); László Czakó (University of Szeged Szeged Hungary Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Teresa Angueira (Hospital General de Tomelloso Ciudad Real Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Eduardo Iyo (Hospital Comarcal de Inca Mallorca Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Ekaterina Yuryevna (Plotnikova Kemerovo State Medical Academy Kuzbass Regional Hepatology Center Kemerovo Russia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Larissa Tarasova (Chuvash State University named after I.N. Ulyanov, the chair of faculty therapy Cheboksary Russia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Ludmila Grigorieva (Chuvash State University named after I.N. Ulyanov, the chair of faculty therapy Cheboksary Russia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Judith Millastre (Hospital de Barbastro Barbastro Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Bruno Richard-Molard (Clinique Bordeaux Nord Bordeaux France Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Aldis Pukitis Paul Stradins (Clinical University Hospital Riga Latvia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Valeriy Kryvy (Crimean State Medical University named after S.I.Georgievskyi Simferopol Ukrania Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Roald Torp (Sykehuset Innlandet, Hamar Hamar Norway Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Albert Tomàs (Consorci Sanitari del Garraf Sant Pere de Ribes Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Edurne Amorena (Complejo Hospitalario de Navarra Pamplona Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Fermin Estremera (Complejo Hospitalario de Navarra Pamplona Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Rossen Nikolov (University Hospital St Ivan Rilski Sofia Bulgaria Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Asghar Quasim (Beacon Hospital Dublin Ireland Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Yury Aleksandrovich Kucheryavyy (Moscow State University of Medicine and Dentistry named after A.I. Evdokimov Moscow Russia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Natalia Baryshnikova (Fisrt St-Petersburg Pavlov State Medical University St Petersburg Russia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Xavier Calvet (Corporació Sanitària Universitària Parc Taulí. CIBERehd, Instituto de Salud Carlos III Departament de Medicina. Universitat Autònoma de Barcelona Sabadell Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Ariadna Figuerola (Corporació Sanitària Universitària Parc Taulí. CIBERehd, Instituto de Salud Carlos III Departament de Medicina. Universitat Autònoma de Barcelona Sabadell Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Marco Romano (Università degli Studi della Campania "Luigi Vanvitelli" Napoli Italy Acquired the data, critically reviewed the manuscript draft and approved the submitted manuscript); Antonietta Gerarda Gravina (Università degli Studi della Campania "Luigi Vanvitelli" Napoli Italy Acquired the data, critically reviewed the manuscript draft and approved the submitted manuscript); Oscar Núñez ("Hospital Uni. Sanitas La Moraleja Madrid Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Fazia Mana (UZ Brussel Jette Belgium Acquired the data, critically reviewed the manuscript draft and approved the submitted manuscript); Pilar Sánchez-Pobre (Hospital Clinico San Carlos Madrid Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Zoya Spassova (University Hospital St. Ivan Rilski Sofia Bulgaria Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Jesús M González-Santiago (Hospital Clínico Universitario. Instituto de Investigación Biomédica de Salamanca (IBSAL). Salamanca Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Ricardo Marcos-Pinto (1. Centro Hospitalar do Porto 2. Institute of Biomedical Sciences Abel Salazar, University of Porto 3. CINTESIS, University of Porto Porto Portugal Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); F Wolfhagen (Albert Schweitzer Ziekenhuis Dordrecht The Netherlands Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Svetlana Cui (Pauls Stradins Clinical University Hospital Riga Latvia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Ivonne Leeuwenburgh (Sint Franciscus Gasthuis Rotterdam The Netherlands Acquired ata, critically reviewed the manuscript draft and approved the submitted manuscript); Driffa Moussata (Lyon Sud Hospital Pierre Benite France Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Adi Lahat-zok (Chaim Sheba medical center and Sackler School of Medicine, Tel Aviv University Israel Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Sergii Hryhorovych (Melashchenko Vinnitsa National Medical University Vinnytsia Ukrania Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Rasmus Goll (University Hospital of North Norway Tromso Norway Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Tatyana Vasilyevna (Zhestkova Ryazan State Medical University Ryazan Russia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Juris Pokrotnieks (Pauls Stradins Clinical University Hospital Riga Latvia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Philippe Émile (Houcke Hôpital Claude Huriez (CHRU) Lille France Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Nadiya Byelyayeva (Donetsk National Medical University Donetsk Ukrania Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Marta Lozano (Lanagran Hospital Quuiron Malaga Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Mette Wildner-Christensen (Odense University Hospital (OUH) Svendborg Denmark Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Bengt Odman (Soder Hospital Stockholm Sweden Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Yana Valerieva (University Hospital Tsaritsa Yoanna-ISUL Sofia Bulgaria Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Alenka Forte (MC Heliks, d.o.o. Trbovlje Slovenia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Antonio Cuadrado (Lavin Hospital Universitario Marqués de Valdecilla Santander Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Patrice Pienkowski (Hospital Center de Montauban Montauban France Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Ilze Kikuste (University of Latvia, Digestive diseases centre GASTRO Riga Latvia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Dag Arne Lihaug Hoff (Aalesund Hospital Aalesund Norway Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Jane Moeller Hansen (Odense University Hospital Odense Denmark Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Konrads Funka (Digestive Diseases Centre GASTRO Riga Latvia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Alla Kononova (Department of General Practice Tver Russia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Sergey Kolbasnikov (The Head of Department of General Practice Tver Russia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Michael Selgrad (Otto-von Guericke University Magdeburg Germany Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Jolanta Sumskiene (Lithuanian University of Health Sciences Hospital Lithuania Lithuania Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Jonathan Hirsch (Meir Medical Center Kfar Saba Israel Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Francisco Javier Zozaya Larequi (Hospital Universitario Donostia San Sebastián Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Alain C Burette (Chirec clinique de la Basilique and clinique Edith Cavell Brussels Belgium Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Nora Dancs Petz-Aladar (Teaching Hospital Gyor Hungary Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Janne Rajala Herttoniemi (Hospital Helsinky Finland Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Christina Reimer (Hvidovre Hospital Hvidovre Denmark Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Diogo Libanio (Gastroenterology Department Instituto Portugues de Oncologia do Porto (IPO-Porto) Porto Portugal Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Pedro Pimentel-Nunes (Gastroenterology Department Instituto Portugues de Oncologia do Porto (IPO-Porto) Porto Portugal Acquired the data, critically reviewed the manuscript draft and approved the submitted manuscript); Ivailo Evstatiev (University Hospital St Ekaterina Sofia Bulgaria Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Juozas Kupcinskas (Lithuanian University of Health Sciences Kaunas Lithuania Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Mikhail Butov (State Budgetary Educational Institution of Higher Professional Education Ryazan State I.P. Pavlov Medical University of the Ministry of Public Health of Russian Federation (SB?IHPE RSMU of Ministry of Public Health of Russian Federation) Department of Propaedeutics of Internal Diseases Ryazan Russia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Peter Mensink (Medisch Spectrum Twente Enschede The Netherlands Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); T Tang (IJsselland Ziekenhuis Capelle aan de Ijssel The Netherlands Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Andrey Yurevich Baranovsky (North-Western State Medical University named after I.I.Mechnicov Saint-Petersburg Russia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Natalya Marchenko (North-Western State Medical University named after I.I. Mechnikov Saint-Patarsburg Russia Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Boris Bastens (CHC Liege Liege Belgium Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Lyudmila Mateva ("University Hospital St. Ivan Rilski Sofia Bulgaria Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Dominique Lamarque (Hôpital Ambroise-Paré Boulogne-Billancourt (Paris) France Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Leonardo Henry (Eusebi Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Gastroenterology and Endoscopy Unit, Policlinico S.Orsola-Malpighi Bologna Italy Acquired the data, critically reviewed the manuscript draft and approved the submitted manuscript); Mario Ribeiro (FMUP/IPATIMUP Porto Portugal Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); M ter Borg (Maxima Medisch Centrum Eindhoven The Netherlands Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Alexander C Ford (Leeds Teaching Hospitals Trust Leeds UK Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Enrique Medina (Consorcio Hospital General de Valencia Valencia Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Manuel Rodriguez-Tellez (Virgen Macarena University Hospital Sevilla Spain Acquired the data, critically reviewed the manuscript draft and approved the submitted manuscript); Francisco José Rancel (Medina Hospital Virgen del Puerto Plasencia Spain Acquired the data, critically reviewed the manuscript draft and approved the submitted manuscript); Elisa Martin (Hospital Virgen del Puerto Plasencia Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Carolina Torres Gonzalez (Hospital de la Ribera Alcira (Valencia) Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript); Lissa Maria Franco (Hospital de Cabueñes Oviedo Spain Acquired data, critically reviewed the manuscript draft and approved the submitted manuscript).

    • Contributors OPN: Scientific Director and member of the project’s Scientific Committee, planned and coordinated the study, designed and programmed the electronic case report form, analysed the data, wrote the manuscript drafts and approved the submitted manuscript. DSB, BT, FL, ML, TR, LK, OS, AG, HS, ATRA, GMB, YN, VL, AT, MV, PB, LGC, TM and VM: acted as national coordinators for their country and as recruiters. Selected national recruiters, collected and helped interpreting data, critically reviewed the manuscript drafts, and approved the submitted manuscript. JCM, AG, KP and CB: acted as non-recruiting national coordinators. Selected national recruiters, helped interpreting data, critically reviewed the manuscript drafts and approved the submitted manuscript. AP-A, DV, LB, MC, LR, JP-L, LL, GF, JM-I, LV, GF and IA: collected and helped interpreting data, critically reviewed the manuscripts’ drafts and approved the submitted manuscript. MC and AG: supervised, coordinated and monitored data collection, interpreted data, critically reviewed the manuscript drafts and approved the submitted manuscript. JG and CF: supervised, analysed and interpreted data, critically reviewed the manuscript drafts and approved the submitted manuscript. IP: Scientific Director and member of the project’s Scientific Committee, critically reviewed the manuscript drafts and approved the submitted manuscript. FM: French National Coordinator and Member of the project’s Scientific Committee, designed the protocol, planned the study, analysed the data, critically reviewed the manuscript drafts and approved the submitted manuscript. CO’M: Irish National Coordinator and Member of the project’s Scientific Committee, designed the protocol, planned the study, collected and analysed the data, critically reviewed the manuscript drafts, and approved the submitted manuscript. JPG: directed the project and the project’s Scientific Committee, obtained funding, designed the protocol and planned the study, acted as Spanish National Coordinator, analysed and interpreted the data, collected patients, critically reviewed the manuscript drafts and approved the final submitted manuscript.

    • Funding This project has been funded by the European Helicobacter and Microbiota Study Group (EHMSG), the Asociación Española de Gastroenterología (AEG) and the Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd).

    • Competing interests JPG has served as speaker, consultant and advisory member for or has received research funding from Mayoly, Allergan and Diasorin. OPN has received a research grant from Allergan. JM-I has served as a consultant for Casen Recordati and has received retribution from Allergan for formative actions. MC-F has received retribution from Allergan for formative actions. PB has served as speaker, consultant and advisory member for or has received research funding from Almirall, Allergan and Reckitt Benckiser. APA has received retribution from Allergan and Mylan for formative actions. DSB has served as lecturer for Astellas, AstraZeneca, KRKA and Abbott.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.

    • Patient consent for publication Not required.

    • Ethics approval CEIM Hospital Universitario de La Princesa. There are two approvals: Hp-EuReg 20-Dec-2012 and Hp-EuReg 15-Jan-2015.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

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