The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology

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  • Jonel Trebicka, JW Goethe University Hospital
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  • Javier Fernandez, European Foundation for Study of Chronic Liver Failure
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  • Maria Papp, Univ Debrecen, University of Debrecen, Dept Ecol
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  • Paolo Caraceni, University of Bologna, Bologna, Italy.
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  • Wim Laleman, Dept. of Radiation Oncology, KU Leuven-University of Leuven, University Hospitals Leuven, Leuven, Belgium.
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  • Carmine Gambino, University of Padova, Padova, Italy
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  • Ilaria Giovo, University Torino, Clinic for Cardiac Surgery, Torino
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  • Frank Erhard Uschner, JW Goethe University Hospital
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  • Cesar Jimenez, Universitat Autonoma de Barcelona
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  • Rajeshwar Mookerjee, Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, United Kingdom.
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  • Thierry Gustot, Royal observatory of Belgium, Ringlaan 3, B-1180 Brussel, Belgium
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  • Agustin Albillos, Alcalá de Henares University
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  • Rafael Bañares, Universidad Complutense
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  • Martin Janicko, Pavol Jozef Safarik University in Kosice
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  • Christian Steib, Department of Urology, University Hospital of Munich, Munich, Germany.
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  • Thomas Reiberger, Medical University Vienna, Vienna
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  • Juan Acevedo, University Hospitals Plymouth NHS Trust
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  • Pietro Gatti, Humanitas Clinical and Research Institute, National Research Council of Italy, Rozzano, Italy.
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  • William Bernal, King's College and King's College Hospital
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  • Stefan Zeuzem, JW Goethe University Hospital
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  • Alexander Zipprich, University Hospital Halle-Wittenberg
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  • Salvatore Piano, University of Padova, Padova, Italy
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  • Thomas Berg, Heart Center Leipzig, University of Leipzig, Leipzig, Germany.
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  • Tony Bruns, Institute of General Practice and Family Medicine, Jena University Hospital, University of Jena, Jena, Germany.
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  • Flemming Bendtsen, Department of Neurorehabilitation, TBI Unit, Copenhagen University Hospital, Glostrup (Satellite Department on Hvidovre Hospital), Hvidovre, Denmark.
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  • Minneke Coenraad, Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands; Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
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  • Manuela Merli, Humanitas Clinical and Research Institute, National Research Council of Italy, Rozzano, Italy.
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  • Rudolf Stauber, Cancer Biology Unit, Department of Dermatology, Medical University of Graz, Graz, Austria; Center for Medical Research, Medical University of Graz, Graz, Austria.
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  • Heinz Zoller, Univ Klin Innsbruck, Medical University of Innsbruck
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  • José Presa Ramos, Associação Protectora dos Diabéticos de Portugal (APDP), Lisbon, Portugal.
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  • Cristina Solè, Hospital Clinic, IDIBAPS and CIBEehd
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  • Germán Soriano, Hospital de la Santa Creu i Sant Pau and CIBERehd
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  • Andrea de Gottardi, Gastroenterology, Clinic for Visceral Surgery and Medicine, Inselspital, University Hospital of Bern, Bern, Switzerland.
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  • Henning Gronbaek
  • Faouzi Saliba, 5LPO-BirdLife France, France
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  • Christian Trautwein, Department of Oncology, Hematology, Hemostaseology and Stem Cell Transplantation, University Hospital Aachen, Medical Faculty, RWTH Aachen University, Aachen, Germany.
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  • Osman Cavit Özdogan, Marmara Univ, Marmara University, Dept Family Med, Istanbul Fac
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  • Sven Francque, Cardiology - Electrophysiology, Antwerp University and University Hospital, Antwerp, Belgium.
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  • Stephen Ryder, University of Nottingham
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  • Pierre Nahon, 5LPO-BirdLife France, France
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  • Manuel Romero-Gomez, Clinical Management Unit of Digestive Diseases, University Hospital Virgen del Rocio, Seville, Spain.
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  • Hans Van Vlierberghe, University Hospital Ghent and SafePedrug, Ghent University, Ghent, Belgium.
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  • Claire Francoz, 5LPO-BirdLife France, France
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  • Michael Manns, Hannover Unified Biobank, Hannover Medical School, Hannover, 30625, Germany.
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  • Elisabet Garcia, European Foundation for Study of Chronic Liver Failure
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  • Manuel Tufoni, University of Bologna, Bologna, Italy.
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  • Alex Amoros, European Foundation for Study of Chronic Liver Failure
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  • Marco Pavesi, European Foundation for Study of Chronic Liver Failure
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  • Cristina Sanchez, European Foundation for the study of Chronic Liver Failure (EF-CLIF), Barcelona, Spain.
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  • Anna Curto, European Foundation for Study of Chronic Liver Failure
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  • PREDICT STUDY group of the EASL-CLIF Consortium

BACKGROUND & AIMS: Acute decompensation (AD) of cirrhosis is defined as the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination thereof, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF). The PREDICT study is a European, prospective, observational study, designed to characterize the clinical course of AD and to identify predictors of ACLF.

METHODS: A total of 1,071 patients with AD were enrolled. We collected detailed pre-specified information on the 3-month period prior to enrollment, and clinical and laboratory data at enrollment. Patients were then closely followed up for 3 months. Outcomes (liver transplantation and death) at 1 year were also recorded.

RESULTS: Three groups of patients were identified. Pre-ACLF patients (n = 218) developed ACLF and had 3-month and 1-year mortality rates of 53.7% and 67.4%, respectively. Unstable decompensated cirrhosis (UDC) patients (n = 233) required ≥1 readmission but did not develop ACLF and had mortality rates of 21.0% and 35.6%, respectively. Stable decompensated cirrhosis (SDC) patients (n = 620) were not readmitted, did not develop ACLF and had a 1-year mortality rate of only 9.5%. The 3 groups differed significantly regarding the grade and course of systemic inflammation (high-grade at enrollment with aggravation during follow-up in pre-ACLF; low-grade at enrollment with subsequent steady-course in UDC; and low-grade at enrollment with subsequent improvement in SDC) and the prevalence of surrogates of severe portal hypertension throughout the study (high in UDC vs. low in pre-ACLF and SDC).

CONCLUSIONS: Acute decompensation without ACLF is a heterogeneous condition with 3 different clinical courses and 2 major pathophysiological mechanisms: systemic inflammation and portal hypertension. Predicting the development of ACLF remains a major future challenge. CLINICALTRIALS.

GOV NUMBER: NCT03056612.

LAY SUMMARY: Herein, we describe, for the first time, 3 different clinical courses of acute decompensation (AD) of cirrhosis after hospital admission. The first clinical course includes patients who develop acute-on-chronic liver failure (ACLF) and have a high short-term risk of death - termed pre-ACLF. The second clinical course (unstable decompensated cirrhosis) includes patients requiring frequent hospitalizations unrelated to ACLF and is associated with a lower mortality risk than pre-ACLF. Finally, the third clinical course (stable decompensated cirrhosis), includes two-thirds of all patients admitted to hospital with AD - patients in this group rarely require hospital admission and have a much lower 1-year mortality risk.

Original languageEnglish
Book seriesJournal of Hepatology
Volume73
Issue4
Pages (from-to)842-854
Number of pages13
ISSN0169-5185
DOIs
Publication statusPublished - Oct 2020

    Research areas

  • Acute complications, Chronic liver disease, Non-elective admission, Outcome, Risk factors

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