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Original research
Hepatic encephalopathy is not a contraindication to pre-emptive TIPS in high-risk patients with cirrhosis with variceal bleeding
  1. Marika Rudler1,2,3,
  2. Virginia Hernández-Gea4,
  3. Bogdan Dumitru Procopet5,6,
  4. Alvaro Giráldez7,
  5. Lucio Amitrano8,
  6. Càndid Villanueva9,10,
  7. Luis Ibañez11,12,
  8. Gilberto Silva-Junior4,
  9. Joan Genesca13,
  10. Christophe Bureau14,
  11. Jonel Trebicka15,
  12. Rafael Bañares16,
  13. Aleksander Krag17,
  14. Elba Llop18,
  15. Wim Laleman19,
  16. Jose Maria Palazon20,
  17. Jose Castellote21,
  18. Susana Rodrigues22,
  19. Lise Lotte Gluud23,
  20. Carlos Noronha Ferreira24,
  21. Nouria Canete25,
  22. Manuel Rodríguez26,
  23. Arnulf Ferlitsch27,
  24. Jose Luis Mundi28,
  25. Henning Gronbaek29,
  26. Manuel Hernandez-Guerra30,
  27. Romano Sassatelli31,
  28. Alessandra Dell’era32,33,
  29. Marco Senzolo34,
  30. Juan G Abraldes35,
  31. Manuel Romero-Gómez36,
  32. Alexander Zipprich37,
  33. Meritxell Casas38,
  34. Helena Masnou39,
  35. Hélène Larrue40,
  36. Massimo Primignani41,
  37. Frederik Nevens42,
  38. Jose Luis Calleja43,44,
  39. Remy Schwarzer27,
  40. Christian Jansen45,
  41. Marie-Angèle Robic40,
  42. Irene Conejo46,
  43. Javier Martínez Gonzalez47,
  44. Maria Vega Catalina48,
  45. Agustín Albillos49,50,
  46. Edilmar Alvarado51,
  47. Maria Anna Guardascione52,
  48. Maxime Mallet1,
  49. Simona Tripon1,
  50. Georgina Casanovas53,
  51. Jaume Bosch54,
  52. Juan-Carlos Garcia-Pagan4,
  53. Dominique Thabut1,2,3
  54. for International Variceal Bleeding Observational Study Group: a Baveno Cooperation
  1. 1 Hepatology and gastroenterology, Unité de Soins Intensifs d’Hépato-Gastro-Entérologie, Groupement Hospitalier APHP-Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Paris, France, Paris, France
  2. 2 Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
  3. 3 Brain-Liver Pitié-Salpêtrière Study Group (BLIPS), APHP-Sorbonne Université, Paris, France
  4. 4 Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, IDIBAPS and CIBERehd, Barcelona, Spain
  5. 5 Gastroenterology, Regional Institute of Gastroenterology and Hepatology 'Octavian Fodor', Cluj-Napoca, Romania
  6. 6 Gastroenterology, University of Medicine and Pharmacy 'Iuliu Hatieganu', Cluj-Napoca, Romania
  7. 7 Hepatology, Hospital Universitario Virgen del Rocío, Sevilla, Spain
  8. 8 Gastroenterology, A. Cardarelli Hospital, Napoli, Italy
  9. 9 Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona Autonomous University, Barcelona, Spain
  10. 10 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
  11. 11 Gastroenterology and Hepatology, Hospital Universitario Gregorio Marañon, Instituto de Investigacion Sanitaria Gregorio Marañon (IiSGM), Universidad Complutense de Madrid, Madrid, Spain
  12. 12 Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
  13. 13 Internal Medicine-Liver Unit, Hospital Universitario Vall d'Hebron, Barcelona, Spain
  14. 14 Hepato-Gastroenterology, University Hospital, Toulouse, France
  15. 15 Translational Hepatology, Department of Internal Medicine I, Goethe-Universitat Frankfurt am Main, Frankfurt am Main, Germany
  16. 16 Gastroenterology, IRYCIS, Hospital General Universitario Gregorio Marañón, Madrid, Spain
  17. 17 Department of Gastroenterology, Odense University Hospital, University of Southern Denmark, Odense, Denmark
  18. 18 Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona and CIBERehd, Barcelona, Spain
  19. 19 Division of Liver and Biliopancreatic Disorders, KU Leuven, University of Leuven, Leuven, Belgium
  20. 20 Hospital General Universitario de Alicante, Alicante, Spain
  21. 21 Digestive Diseases, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain
  22. 22 Department of Gastroenterology, Faculty of Medicine, Centro Hospitalar São João, Porto, Portugal
  23. 23 Gastrounit, Medical Division, University Hospital of Hvidovre, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  24. 24 Gastroenterology, Hospital de Santa Maria, Lisbon, Portugal
  25. 25 Liver Section, Gastroenterology Department, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain
  26. 26 Department of Gastroenterology, Hospital Central de Asturias, Oviedo, Spain
  27. 27 Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
  28. 28 Department of Gastroenterology, University Hospital San Cecilio, Grenada, Spain
  29. 29 Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
  30. 30 Liver Unit, University Hospital of the Canary Islands, Santa Cruz de Tenerife, Spain
  31. 31 Endoscopy Unit, IRCCS Santa Maria Nuova, Reggio Emilia, Italy
  32. 32 Dipartimento di Scienze Biomediche e Cliniche, Università degli Studi di Milano, Milano, Italy
  33. 33 UOC Gastroenterologia ed Endoscopia, Aziende Socio Sanitarie Territoriale Fatebenefratelli Sacco, Milano, Italy
  34. 34 Department of Surgical and Gastroenterological Sciences, Multivisceral Transplant Unit, University of Padova, Padova, Italy
  35. 35 Cirrhosis Care Clinic, University of Alberta, Edmonton, Alberta, Canada
  36. 36 Unit for The Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario de Valme, Sevilla, Spain
  37. 37 First Department of Internal Medicine, Martin-Luther-University, Halle, Germany
  38. 38 Liver Unit, Department of Gastroenterology, Corporación Sanitaria Parc Taulí, Sabadell, Spain
  39. 39 Hospital Universitari Germans Trias i Pujol, Universitat Autònoma Barcelona, Barcelona, Spain
  40. 40 Service D’hepato-Gastro-Enterologie, CHU Purpan, Toulouse, France
  41. 41 Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
  42. 42 Hepatology, UZ Leuven, Leuven, Belgium
  43. 43 Gastroenterology and Hepatology, IDIPHISA, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Spain
  44. 44 (CIBERehd), Instituto de Salud Carlos III, Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas, Madrid, Spain
  45. 45 Internal Medicine I, University of Bonn, Bonn, Germany
  46. 46 Liver Unit, Hospital Universitario Vall d’Hebron, Vall d’Hebron Institute of Research (VHIR), Universitat Autònoma de Barcelona and CIBERehd, Barcelona, Spain
  47. 47 Department of Gastroenterology, Hospital Universitario Ramón y Cajal, IRYCIS, University of Alcalá, Madrid, Spain
  48. 48 Servicio de Medicina de Aparato Digestivo Gregorio Marañón, Hospital General Universitario Gregorio Marañón, CIBERehd, Barcelona, Spain
  49. 49 Hepatology, Hospital Ramon y Cajal, Madrid, Spain
  50. 50 Universidad de Alcala de Henares, Madrid, Spain
  51. 51 Gastroenterology, Hospital de la Santa Creu i Sant Pau Institut de Recerca, Barcelona, Spain
  52. 52 Gastroenterology Unit, Ospedale A Cardarelli, Naples, Italy
  53. 53 Biostatistics Unit, Faculty of Medicine, Universitat Autònoma Barcelona, Barcelona, Spain
  54. 54 Department of Biomedical Research, Bern University, Hepatology, Inselspital, Bern, Switzerland
  1. Correspondence to Dr Marika Rudler, Hopitaux Universitaires Pitie Salpetriere-Charles Foix, Paris, France; marika_rudler{at}


Background A pre-emptive transjugular intrahepatic portosystemic shunt (pTIPS) reduces mortality in high-risk patients with cirrhosis (Child-Pugh C/B+active bleeding) with acute variceal bleeding (AVB). Real-life studies point out that <15% of patients eligible for pTIPS ultimately undergo transjugular intrahepatic portosystemic shunt (TIPS) due to concerns about hepatic encephalopathy (HE). The outcome of patients undergoing pTIPS with HE is unknown. We aimed to (1) assess the prevalence of HE in patients with AVB; (2) evaluate the outcome of patients presenting HE at admission after pTIPS; and (3) determine if HE at admission is a risk factor for death and post-TIPS HE.

Patients and methods This is an observational study including 2138 patients from 34 centres between October 2011 and May 2015. Placement of pTIPS was based on individual centre policy. Patients were followed up to 1 year, death or liver transplantation.

Results 671 of 2138 patients were considered at high risk, 66 received pTIPS and 605 endoscopic+drug treatment. At admission, HE was significantly more frequent in high-risk than in low-risk patients (39.2% vs 10.6%, p<0.001). In high-risk patients with HE at admission, pTIPS was associated with a lower 1-year mortality than endoscopic+drug (HR 0.374, 95% CI 0.166 to 0.845, p=0.0181). The incidence of HE was not different between patients treated with pTIPS and endoscopic+drug (38.2% vs 38.7%, p=0.9721), even in patients with HE at admission (56.4% vs 58.7%, p=0.4594). Age >56, shock, Model for End-Stage Liver Disease score >15, endoscopic+drug treatment and HE at admission were independent factors of death in high-risk patients.

Conclusion pTIPS is associated with better survival than endoscopic treatment in high-risk patients with cirrhosis with variceal bleeding displaying HE at admission.

  • cirrhosis
  • hepatic encephalopathy
  • oesophageal varices

Data availability statement

Data may be obtained from a third party and are not publicly available.

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Data availability statement

Data may be obtained from a third party and are not publicly available.

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  • Twitter @virginiaHdezGea, @GilbertoSilva01, @mromerogomez

  • Collaborators Baveno Cooperation: an EASL consortium.

  • Contributors MR, DT: study concept. GC, FN: statistical analysis. VH-G, BP, AG, LA, CV, LI, GS-J, JG, CB, JT, RB, AK, EL, WL, JMP, JC, SR, LLG, CNF, NC, MR, AF, RS, JLM, HG, MH-G, RS, AD'E, MS, JGA, M-RG, AZ, MC, HM, MP, FN, JLC, CJ, M-AR, IC, MVC, EA, MM, ST, JB, J-CG-P: management of patients, acquisition of data, critical review of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests CB has received speaker fees from GORE and is a board member in Alfa Wassemran/Norgine. VH-G, AG, JB, AA, DT and FN have received speaker fees from GORE. J-CG-P has consultant fees from GORE, and Shionogi and Cook grants from GORE and Novartis. JT has speaking and/or consulting fees from GORE, Bayer, Alexion, MSD, Gilead, Intercept, Norgine, Grifols, Versantis and Martin Pharmaceuticals. RB has received speaker fees from GORE and Grifols, unrelated to the submitted work.

  • 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.

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

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.