Jonel Trebicka1, Wenyi Gu2, Luis Ibáñez-Samaniego3, Virginia Hernández-Gea4, Carla Pitarch5, Elisabet Garcia5, Bogdan Procopet6, Álvaro Giráldez7, Lucio Amitrano8, Candid Villanueva9, Dominique Thabut10, Gilberto Silva-Junior11, Javier Martinez12, Joan Genescà13, Cristophe Bureau14, Elba Llop15, Wim Laleman16, Jose Maria Palazon17, Jose Castellote18, Susanag Rodrigues19, Liselotte Gluud20, Carlos Noronha Ferreira21, Rafael Barcelo22, Nuria Cañete23, Manuel Rodríguez24, Arnulf Ferlitsch25, Jose Luis Mundi26, Henning Gronbaek27, Manuel Hernández-Guerra28, Romano Sassatelli29, Alessandra Dell'Era30, Marco Senzolo31, Juan G Abraldes32, Manuel Romero-Gómez33, Alexander Zipprich34, Meritxell Casas35, Helena Masnou36, Massimo Primignani37, Emmanuel Weiss5, Maria-Vega Catalina3, Hans-Peter Erasmus38, Frank Erhard Uschner38, Martin Schulz38, Maximilian J Brol39, Michael Praktiknjo39, Johannes Chang39, Aleksander Krag40, Frederik Nevens16, Jose Luis Calleja15, Marie Angèle Robic14, Irene Conejo13, Agustin Albillos41, Marika Rudler10, Edilmar Alvarado9, Maria Anna Guardascione8, Marcel Tantau6, Jaime Bosch42, Ferran Torres43, Marco Pavesi5, Juan Carlos Garcia-Pagán4, Christian Jansen39, Rafael Bañares44. 1. Department of Internal Medicine I, University of Frankfurt, Frankfurt, Germany; Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; European Foundation for the Study of Chronic Liver Failure - EF CLIF, Barcelona, Spain; Institute for Bioengineering of Catalonia, Barcelona, Spain. Electronic address: jonel.trebicka@kgu.de. 2. Department of Internal Medicine I, University of Frankfurt, Frankfurt, Germany; European Foundation for the Study of Chronic Liver Failure - EF CLIF, Barcelona, Spain; Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 3. Servicio de Medicina de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, liSGM, CIBERehd, Madrid, Spain. 4. Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi I i Sunyer, IMDIM, University of Barcelona, Barcelona, Spain, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver); Centro de Investigación Biomédica Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain. 5. European Foundation for the Study of Chronic Liver Failure - EF CLIF, Barcelona, Spain. 6. Regional Institute of Gastroenterology and Hepatology "Octavian Fodor", Hepatology Department and "Iuliu Hatieganu" University of Medicine and Pharmacy, 3rd Medical Clinic, Cluj-Napoca, Romania. 7. Clinical Management Unit of Digestive Diseases, University Hospital Virgen del Rocío, Seville, Spain. 8. Gastroenterology Unit, Ospedale A Cardarelli, Naples, Italy. 9. Centro de Investigación Biomédica Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain; Servei de Patologia Digestiva, Hospital de la Santa Creu i Sant Pau and CIBERehd, Barcelona, Spain. 10. Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Paris Sorbonne Université, Paris, France. 11. Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi I i Sunyer, IMDIM, University of Barcelona, Barcelona, Spain, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver). 12. Department of Gastroenterology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), University of Alcalá, CIBERehd, Madrid, Spain. 13. Centro de Investigación Biomédica Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain; Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Research (VHIR), Universitat Autònoma de Barcelona and CIBERehd, Barcelona, Spain. 14. Department of Hepatology, Rangueil Hospital, CHU Toulouse, University Paul Sabatier of Toulouse, France. 15. Centro de Investigación Biomédica Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain; Liver Unit, Hospital U, Puerta de Hierro, Universidad Autònoma de Madrid, CIBERehd, Madrid, Spain. 16. Department of Gastroenterology and Hepatology, University Hospital KU Leuven, Leuven, Belgium. 17. Hospital General Universitario de Alicante, Alicante, Spain. 18. Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Barcelona, Spain. 19. Gastroenterology and Hepatology Department, Centro Hospitalar São João, Porto, Portugal. 20. Gastrounit, Medical Division, University Hospital of Hvidovre, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 21. Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria - Centro Hospitalar Lisboa Norte, Lisbon, Portugal. 22. Medical Statistics Core Facility, Institut D'Investigacions Biomédiques August Pi i Sunyer, Hospital Clinic Barcelona, Barcelona, Spain. 23. Liver Section, Gastroenterology Department, Hospital del Mar, Universitat Autònoma de Barcelona, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. 24. Department of Gastroenterology, Hospital Central de Asturias, Oviedo, Spain. 25. Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria. 26. Department of Gastroenterology, University Hospital San Cecilio, Granada, Spain. 27. Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark. 28. Gastroenterology Department, University Hospital of the Canary Islands, La Laguna, Tenerife, Spain. 29. Unit of Gastroenterology and Digestive Endoscopy, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy. 30. Gastroenterology Unit, ASST Fatebenefratelli Sacco, Department of Clinical and Biomedical Sciences, University of the Studies of Milan, Milan, Italy. 31. Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy. 32. Cirrhosis Care Clinic, Division of Gastroenterology (Liver Unit), CEGIIR, University of Alberta, Edmonton, Canada. 33. Centro de Investigación Biomédica Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain; Unidad de Hepatología, Hospital Universitario de Valme, CIBERehd, Sevilla, Spain. 34. First Department of Internal Medicine, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany. 35. Hepatology Unit, Digestive Disease Department Hospital de Sabadell, Universitat Autònoma de Barcelona, Sabadell, Spain. 36. Hospital Universitari Germans Trias i Pujol, Universitat Autònoma Barcelona, Badalona, Spain. 37. Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, CRC "A.M.and A.Miglaivacca" Center for Liver Disease, Milan, Italy. 38. Department of Internal Medicine I, University of Frankfurt, Frankfurt, Germany. 39. Department of Internal Medicine I, University of Bonn, Bonn, Germany. 40. Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark. 41. Centro de Investigación Biomédica Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain; Department of Gastroenterology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), University of Alcalá, CIBERehd, Madrid, Spain. 42. Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi I i Sunyer, IMDIM, University of Barcelona, Barcelona, Spain, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver); Centro de Investigación Biomédica Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain; Swiss Liver Centre, Inselspital, Bern University, Bern, Switzerland. 43. Medical Statistics Core Facility, Institut D'Investigacions Biomédiques August Pi i Sunyer, Hospital Clinic Barcelona, Barcelona, Spain; Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. 44. Centro de Investigación Biomédica Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain; Gregorio Marañón University General Hospital, Gregorio Marañón Sanitary Research Institute, Faculty of Medicine, Complutense University of Madrid, Spain.
Abstract
BACKGROUND & AIMS: The relationship between acute-on-chronic liver failure (ACLF) and acute variceal bleeding (AVB) is poorly understood. Specifically, the prevalence and prognosis of ACLF in the context of AVB is unclear, while the role of transjugular intrahepatic portosystemic shunt (TIPS) in the management in patients with ACLF has not been described to date. METHODS: A multicenter, international, observational study was conducted in 2,138 patients from 34 centers between 2011 and 2015. ACLF was defined and graded according to the EASL-CLIF consortium definition. Placement of pre-emptive TIPS (pTIPS) was based on individual center policy. Patients were followed-up for 1 year, until death or liver transplantation. Cox regression and competing risk models (Gray's test) were used to identify independent predictors of rebleeding or mortality. RESULTS: At admission, 380/2,138 (17.8%) patients had ACLF according to EASL-CLIF criteria (grade 1: 38.7%; grade 2: 39.2%; grade 3: 22.1%). The 42-day rebleeding (19% vs. 10%; p <0.001) and mortality (47% vs. 10%; p <0.001) rates were higher in patients with ACLF and increased with ACLF grades. Of note, the presence of ACLF was independently associated with rebleeding and mortality. pTIPS placement improved survival in patients with ACLF at 42 days and 1 year. This effect was also observed in propensity score matching analysis of 66 patients with ACLF, of whom 44 received pTIPs and 22 did not. CONCLUSIONS: This large multicenter international real-life study identified ACLF at admission as an independent predictor of rebleeding and mortality in patients with AVB. Moreover, pTIPS was associated with improved survival in patients with ACLF and AVB. LAY SUMMARY: Acute variceal bleeding is a deadly complication of liver cirrhosis that results from severe portal hypertension. This study demonstrates that the presence of acute-on-chronic liver failure (ACLF) is the strongest predictor of mortality in patients with acute variceal bleeding. Importantly, patients with ACLF and acute variceal (re)bleeding benefit from pre-emptive (early) placement of a transjugular intrahepatic portosystemic shunt.
BACKGROUND & AIMS: The relationship between acute-on-chronic liver failure (ACLF) and acute variceal bleeding (AVB) is poorly understood. Specifically, the prevalence and prognosis of ACLF in the context of AVB is unclear, while the role of transjugular intrahepatic portosystemic shunt (TIPS) in the management in patients with ACLF has not been described to date. METHODS: A multicenter, international, observational study was conducted in 2,138 patients from 34 centers between 2011 and 2015. ACLF was defined and graded according to the EASL-CLIF consortium definition. Placement of pre-emptive TIPS (pTIPS) was based on individual center policy. Patients were followed-up for 1 year, until death or liver transplantation. Cox regression and competing risk models (Gray's test) were used to identify independent predictors of rebleeding or mortality. RESULTS: At admission, 380/2,138 (17.8%) patients had ACLF according to EASL-CLIF criteria (grade 1: 38.7%; grade 2: 39.2%; grade 3: 22.1%). The 42-day rebleeding (19% vs. 10%; p <0.001) and mortality (47% vs. 10%; p <0.001) rates were higher in patients with ACLF and increased with ACLF grades. Of note, the presence of ACLF was independently associated with rebleeding and mortality. pTIPS placement improved survival in patients with ACLF at 42 days and 1 year. This effect was also observed in propensity score matching analysis of 66 patients with ACLF, of whom 44 received pTIPs and 22 did not. CONCLUSIONS: This large multicenter international real-life study identified ACLF at admission as an independent predictor of rebleeding and mortality in patients with AVB. Moreover, pTIPS was associated with improved survival in patients with ACLF and AVB. LAY SUMMARY:Acute variceal bleeding is a deadly complication of liver cirrhosis that results from severe portal hypertension. This study demonstrates that the presence of acute-on-chronic liver failure (ACLF) is the strongest predictor of mortality in patients with acute variceal bleeding. Importantly, patients with ACLF and acute variceal (re)bleeding benefit from pre-emptive (early) placement of a transjugular intrahepatic portosystemic shunt.
Authors: Lukas Sturm; Michael Praktiknjo; Dominik Bettinger; Jan P Huber; Lara Volkwein; Arthur Schmidt; Rafael Kaeser; Johannes Chang; Christian Jansen; Carsten Meyer; Daniel Thomas; Robert Thimme; Jonel Trebicka; Michael Schultheiß Journal: Hepatol Commun Date: 2021-01-05
Authors: Johannes Chang; Avend Bamarni; Nina Böhling; Xin Zhou; Leah-Marie Klein; Jonathan Meinke; Georg Daniel Duerr; Philipp Lingohr; Sven Wehner; Maximilian J Brol; Jürgen K Rockstroh; Jörg C Kalff; Steffen Manekeller; Carsten Meyer; Ulrich Spengler; Christian Jansen; Vicente Arroyo; Christian P Strassburg; Jonel Trebicka; Michael Praktiknjo Journal: Hepatol Commun Date: 2021-03-26
Authors: Lorenz Balcar; Georg Semmler; Katharina Pomej; Benedikt Simbrunner; David Bauer; Lukas Hartl; Mathias Jachs; Rafael Paternostro; Theresa Bucsics; Matthias Pinter; Michael Trauner; Mattias Mandorfer; Thomas Reiberger; Bernhard Scheiner Journal: United European Gastroenterol J Date: 2021-05 Impact factor: 4.623
Authors: Justin R Boike; Bartley G Thornburg; Sumeet K Asrani; Michael B Fallon; Brett E Fortune; Manhal J Izzy; Elizabeth C Verna; Juan G Abraldes; Andrew S Allegretti; Jasmohan S Bajaj; Scott W Biggins; Michael D Darcy; Maryjane A Farr; Khashayar Farsad; Guadalupe Garcia-Tsao; Shelley A Hall; Caroline C Jadlowiec; Michael J Krowka; Jeanne Laberge; Edward W Lee; David C Mulligan; Mitra K Nadim; Patrick G Northup; Riad Salem; Joseph J Shatzel; Cathryn J Shaw; Douglas A Simonetto; Jonathan Susman; K Pallav Kolli; Lisa B VanWagner Journal: Clin Gastroenterol Hepatol Date: 2021-07-15 Impact factor: 13.576