Rebleeding and mortality risk are increased by ACLF but reduced by pre-emptive TIPS.


Journal

Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886

Informations de publication

Date de publication:
11 2020
Historique:
received: 24 01 2020
revised: 07 04 2020
accepted: 09 04 2020
pubmed: 28 4 2020
medline: 16 11 2021
entrez: 28 4 2020
Statut: ppublish

Résumé

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. 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. 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. 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 32339602
pii: S0168-8278(20)30236-1
doi: 10.1016/j.jhep.2020.04.024
pii:
doi:

Types de publication

Journal Article Multicenter Study Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1082-1091

Commentaires et corrections

Type : CommentIn
Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest Christophe Bureau has received speaker fees from GORE and is a board member of Alfawassemran/Norgine. Virginia Hernández - Gea, Álvaro Giráldez, Jaume Bosch, Agustin Albillos, Dominique Thabut, Michael Praktiknjo and Frederik Nevens have received speaker fees from GORE. Juan Carlos Garcia – Pagan has received consultant fees from GORE, Shionogi and Cook grants from GORE and Novartis. Jonel Trebicka has received speaking and/or consulting fees from GORE, Bayer, Alexion, MSD, Gilead, Intercept, Norgine, Grifols, Versantis, and Martin Pharmaceutical, and Rafael Bañares has received speaker fees from GORE and Grifols, unrelated to the submitted work. Please refer to the accompanying ICMJE disclosure forms for further details.

Auteurs

Jonel Trebicka (J)

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.

Wenyi Gu (W)

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.

Luis Ibáñez-Samaniego (L)

Servicio de Medicina de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, liSGM, CIBERehd, Madrid, Spain.

Virginia Hernández-Gea (V)

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.

Carla Pitarch (C)

European Foundation for the Study of Chronic Liver Failure - EF CLIF, Barcelona, Spain.

Elisabet Garcia (E)

European Foundation for the Study of Chronic Liver Failure - EF CLIF, Barcelona, Spain.

Bogdan Procopet (B)

Regional Institute of Gastroenterology and Hepatology "Octavian Fodor", Hepatology Department and "Iuliu Hatieganu" University of Medicine and Pharmacy, 3rd Medical Clinic, Cluj-Napoca, Romania.

Álvaro Giráldez (Á)

Clinical Management Unit of Digestive Diseases, University Hospital Virgen del Rocío, Seville, Spain.

Lucio Amitrano (L)

Gastroenterology Unit, Ospedale A Cardarelli, Naples, Italy.

Candid Villanueva (C)

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.

Dominique Thabut (D)

Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Paris Sorbonne Université, Paris, France.

Gilberto Silva-Junior (G)

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).

Javier Martinez (J)

Department of Gastroenterology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), University of Alcalá, CIBERehd, Madrid, Spain.

Joan Genescà (J)

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.

Cristophe Bureau (C)

Department of Hepatology, Rangueil Hospital, CHU Toulouse, University Paul Sabatier of Toulouse, France.

Elba Llop (E)

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.

Wim Laleman (W)

Department of Gastroenterology and Hepatology, University Hospital KU Leuven, Leuven, Belgium.

Jose Maria Palazon (JM)

Hospital General Universitario de Alicante, Alicante, Spain.

Jose Castellote (J)

Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Barcelona, Spain.

Susanag Rodrigues (S)

Gastroenterology and Hepatology Department, Centro Hospitalar São João, Porto, Portugal.

Liselotte Gluud (L)

Gastrounit, Medical Division, University Hospital of Hvidovre, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Carlos Noronha Ferreira (CN)

Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria - Centro Hospitalar Lisboa Norte, Lisbon, Portugal.

Rafael Barcelo (R)

Medical Statistics Core Facility, Institut D'Investigacions Biomédiques August Pi i Sunyer, Hospital Clinic Barcelona, Barcelona, Spain.

Nuria Cañete (N)

Liver Section, Gastroenterology Department, Hospital del Mar, Universitat Autònoma de Barcelona, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.

Manuel Rodríguez (M)

Department of Gastroenterology, Hospital Central de Asturias, Oviedo, Spain.

Arnulf Ferlitsch (A)

Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.

Jose Luis Mundi (JL)

Department of Gastroenterology, University Hospital San Cecilio, Granada, Spain.

Henning Gronbaek (H)

Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.

Manuel Hernández-Guerra (M)

Gastroenterology Department, University Hospital of the Canary Islands, La Laguna, Tenerife, Spain.

Romano Sassatelli (R)

Unit of Gastroenterology and Digestive Endoscopy, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.

Alessandra Dell'Era (A)

Gastroenterology Unit, ASST Fatebenefratelli Sacco, Department of Clinical and Biomedical Sciences, University of the Studies of Milan, Milan, Italy.

Marco Senzolo (M)

Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy.

Juan G Abraldes (JG)

Cirrhosis Care Clinic, Division of Gastroenterology (Liver Unit), CEGIIR, University of Alberta, Edmonton, Canada.

Manuel Romero-Gómez (M)

Centro de Investigación Biomédica Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain; Unidad de Hepatología, Hospital Universitario de Valme, CIBERehd, Sevilla, Spain.

Alexander Zipprich (A)

First Department of Internal Medicine, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.

Meritxell Casas (M)

Hepatology Unit, Digestive Disease Department Hospital de Sabadell, Universitat Autònoma de Barcelona, Sabadell, Spain.

Helena Masnou (H)

Hospital Universitari Germans Trias i Pujol, Universitat Autònoma Barcelona, Badalona, Spain.

Massimo Primignani (M)

Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, CRC "A.M.and A.Miglaivacca" Center for Liver Disease, Milan, Italy.

Emmanuel Weiss (E)

European Foundation for the Study of Chronic Liver Failure - EF CLIF, Barcelona, Spain.

Maria-Vega Catalina (MV)

Servicio de Medicina de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, liSGM, CIBERehd, Madrid, Spain.

Hans-Peter Erasmus (HP)

Department of Internal Medicine I, University of Frankfurt, Frankfurt, Germany.

Frank Erhard Uschner (FE)

Department of Internal Medicine I, University of Frankfurt, Frankfurt, Germany.

Martin Schulz (M)

Department of Internal Medicine I, University of Frankfurt, Frankfurt, Germany.

Maximilian J Brol (MJ)

Department of Internal Medicine I, University of Bonn, Bonn, Germany.

Michael Praktiknjo (M)

Department of Internal Medicine I, University of Bonn, Bonn, Germany.

Johannes Chang (J)

Department of Internal Medicine I, University of Bonn, Bonn, Germany.

Aleksander Krag (A)

Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.

Frederik Nevens (F)

Department of Gastroenterology and Hepatology, University Hospital KU Leuven, Leuven, Belgium.

Jose Luis Calleja (JL)

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.

Marie Angèle Robic (MA)

Department of Hepatology, Rangueil Hospital, CHU Toulouse, University Paul Sabatier of Toulouse, France.

Irene Conejo (I)

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.

Agustin Albillos (A)

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.

Marika Rudler (M)

Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Paris Sorbonne Université, Paris, France.

Edilmar Alvarado (E)

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.

Maria Anna Guardascione (MA)

Gastroenterology Unit, Ospedale A Cardarelli, Naples, Italy.

Marcel Tantau (M)

Regional Institute of Gastroenterology and Hepatology "Octavian Fodor", Hepatology Department and "Iuliu Hatieganu" University of Medicine and Pharmacy, 3rd Medical Clinic, Cluj-Napoca, Romania.

Jaime Bosch (J)

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.

Ferran Torres (F)

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.

Marco Pavesi (M)

European Foundation for the Study of Chronic Liver Failure - EF CLIF, Barcelona, Spain.

Juan Carlos Garcia-Pagán (JC)

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.

Christian Jansen (C)

Department of Internal Medicine I, University of Bonn, Bonn, Germany.

Rafael Bañares (R)

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.

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