The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology
Authors: Jonel Trebicka, Javier Fernandez, Maria Papp, Paolo Caraceni, Wim Laleman, Carmine Gambino, Ilaria Giovo, Frank Erhard Uschner, Cesar Jimenez, Rajeshwar Mookerjee, Thierry Gustot, Agustin Albillos, Rafael Bañares, Martin Janicko, Christian Steib, Thomas Reiberger, Juan Acevedo, Pietro Gatti, William Bernal, Stefan Zeuzem, Alexander Zipprich, Salvatore Piano, Thomas Berg, Tony Bruns, Flemming Bendtsen, Minneke Coenraad, Manuela Merli, Rudolf Stauber, Heinz Zoller, José Presa Ramos, Cristina Solè, Germán Soriano, Andrea de Gottardi, Henning Gronbaek, Faouzi Saliba, Christian Trautwein, Osman Cavit Özdogan, Sven Francque, Stephen Ryder, Pierre Nahon, Manuel Romero-Gomez, Hans Van Vlierberghe, Claire Francoz, Michael Manns, Elisabet Garcia, Manuel Tufoni, Alex Amoros, Marco Pavesi, Cristina Sanchez, Anna Curto, Carla Pitarch, Antonella Putignano, Esau Moreno, Debbie Shawcross, Ferran Aguilar, Joan Clària, Paola Ponzo, Christian Jansen, Zsuzsanna Vitalis, Giacomo Zaccherini, Boglarka Balogh, Victor Vargas, Sara Montagnese, Carlo Alessandria, Mauro Bernardi, Pere Ginès, Rajiv Jalan, Richard Moreau, Paolo Angeli, Vicente Arroyo, Miriam Maschmeier, David Semela, Laure Elkrief, Ahmed Elsharkawy, Tamas Tornai, Istvan Tornai, Istvan Altorjay, Agnese Antognoli, Maurizio Baldassarre, Martina Gagliardi, Eleonora Bertoli, Sara Mareso, Alessandra Brocca, Daniela Campion, Giorgio Maria Saracco, Martina Rizzo, Jennifer Lehmann, Alessandra Pohlmann, Michael Praktiknjo, Robert Schierwagen, Elsa Solà, Nesrine Amari, Miguel Rodriguez, Frederik Nevens, Ana Clemente, Peter Jarcuska, Alexander Gerbes, Mattias Mandorfer, Christoph Welsch, Emanuela Ciraci, Vish Patel, Cristina Ripoll, Adam Herber, Paul Horn, Karen Vagner Danielsen, Lise Lotte Gluud, Jelte Schaapman, Oliviero Riggio, Florian Rainer, Jörg Tobiasch Moritz, Mónica Mesquita, Edilmar Alvarado-Tapias, Osagie Akpata, Peter Lykke Eriksen, Didier Samuel, Sylvie Tresson, Pavel Strnad, Roland Amathieu, Macarena Simón-Talero, Francois Smits, Natalie van den Ende, Javier Martinez, Rita Garcia, Daniel Markwardt, Harald Rupprechter, Cornelius Engelmann
Journal: Journal of Hepatology (2020)

•Patients with acutely decompensated cirrhosis without ACLF develop 3 different clinical courses.•Patients with pre-ACLF develop ACLF within 90 days and have high systemic inflammation and mortality.•Patients with unstable decompensated cirrhosis suffer from complications of severe portal hypertension.•Patients with stable decompensated cirrhosis have less frequent complications and lower 1-year mortality risk. Background & AimsAcute 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.MethodsA 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.ResultsThree 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).ConclusionsAcute 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 numberNCT03056612.Lay summaryHerein, 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. 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. 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. 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). 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.