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PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis

2020; Elsevier BV; Volume: 74; Issue: 5 Linguagem: Inglês

10.1016/j.jhep.2020.11.019

1600-0641

Jonel Trebicka, Javier Fernández, Mária Papp, Paolo Caraceni, Wim Laleman, Carmine Gambino, Ilaria Giovo, Frank Erhard Uschner, Christian Jansen, César Jiménez, Rajeshwar P. Mookerjee, Thierry Gustot, Agustı́n Albillos, Rafael Bañares, Peter Jarčuška, Christian J. Steib, Thomas Reiberger, Juan Acevedo, Pietro Gatti, Debbie L. Shawcross, Stefan Zeuzem, Alexander Zipprich, Salvatore Piano, Thomas Berg, Tony Bruns, Karen Vagner Danielsen, Minneke J. Coenraad, Manuela Merli, Rudolf Stauber, Heinz Zoller, José Presa Ramos, Cristina Solé, Germán Soriano, Andrea De Gottardi, Henning Grønbæk, Faouzi Saliba, Christian Trautwein, Haluk Tarık Kani, Sven Francque, Stephen Ryder, Pierre Nahon, Manuel Romero‐Gómez, Hans Van Vlierberghe, Claire Francoz, Michael P. Manns, Elisabet García, Manuel Tufoni, Àlex Amorós, Marco Pavesi, Cristina Sánchez, Michael Praktiknjo, Anna Curto, Carla Pitarch, Antonella Putignano, Esau Moreno, William Bernal, Ferrán Aguilar, J. J. Clariá, Paola Ponzo, Zsuzsanna Vitális, Giacomo Zaccherini, Boglárka Balogh, Alexander L. Gerbes, Vı́ctor Vargas, Carlo Alessandria, Mauro Bernardi, Pere Ginés, Richard Moreau, Paolo Angeli, Rajiv Jalan, Vicente Arroyo, Miriam Maschmeier, David Semela, Laure Elkrief, Ahmed M. Elsharkawy, Tamás Tornai, István Tornai, I Altorjay, Agnese Antognoli, Maurizio Baldassarre, Martina Gagliardi, Eleonora Bertoli, Sara Mareso, Alessandra Brocca, Daniela Campion, Giorgio Maria Saracco, Martina Rizzo, Jennifer Lehmann, Alessandra Pohlmann, Maximilian Joseph Brol, Johannes Chang, Robert Schierwagen, Elsa Solà, Nesrine Amari, Miguel Ángel Morán Rodríguez, Frederik Nevens, Ana Clemente, Martin Janíčko, Daniel Markwardt, Mattias Mandorfer, Christoph Welsch, T Welzel, Emanuela Ciracì, Vish Patel, Cristina Ripoll, Adam Herber, Paul Horn, Flemming Bendtsen, Lise Lotte Gluud, Jelte J. Schaapman, Oliviero Riggio, Florian Rainer, Jörg Tobiasch Moritz, Mónica Mesquita, Edilmar Alvarado‐Tápias, O Akpata, Luise Aamann, Didier Samuel, Sylvie Tresson, Pavel Strnad, Roland Amathieu, Macarena Simón‐Talero, Francois Smits, Natalie Van den Ende, Javier Martínez, Rita García‐Martínez, Harald Rupprechter, Cornelius Engelmann, Osman Özdoğan,

Drug-Induced Hepatotoxicity and Protection

•Bacterial infections and/or severe alcoholic hepatitis are the major precipitants of acute decompensation and ACLF.•The type of precipitating event had no association with survival.•The number of identifiable events was significantly associated with surrogates of systemic inflammation and increased 90-day mortality.•Adequate first-line antibiotic treatment of proven bacterial infections reduced ACLF development and improved 90-day survival.•Strategies to prevent or treat precipitating events may improve outcome in decompensated cirrhosis. Background & AimsAcute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (AD-No ACLF), or with ACLF (AD-ACLF), defined by organ failure(s). Herein, we aimed to analyze and characterize the precipitants leading to both of these AD phenotypes.MethodsThe multicenter, prospective, observational PREDICT study (NCT03056612) included 1,273 non-electively hospitalized patients with AD (No ACLF = 1,071; ACLF = 202). Medical history, clinical data and laboratory data were collected at enrolment and during 90-day follow-up, with particular attention given to the following characteristics of precipitants: induction of organ dysfunction or failure, systemic inflammation, chronology, intensity, and relationship to outcome.ResultsAmong various clinical events, 4 distinct events were precipitants consistently related to AD: proven bacterial infections, severe alcoholic hepatitis, gastrointestinal bleeding with shock and toxic encephalopathy. Among patients with precipitants in the AD-No ACLF cohort and the AD-ACLF cohort (38% and 71%, respectively), almost all (96% and 97%, respectively) showed proven bacterial infection and severe alcoholic hepatitis, either alone or in combination with other events. Survival was similar in patients with proven bacterial infections or severe alcoholic hepatitis in both AD phenotypes. The number of precipitants was associated with significantly increased 90-day mortality and was paralleled by increasing levels of surrogates for systemic inflammation. Importantly, adequate first-line antibiotic treatment of proven bacterial infections was associated with a lower ACLF development rate and lower 90-day mortality.ConclusionsThis study identified precipitants that are significantly associated with a distinct clinical course and prognosis in patients with AD. Specific preventive and therapeutic strategies targeting these events may improve outcomes in patients with decompensated cirrhosis.Lay summaryAcute decompensation (AD) of cirrhosis is characterized by a rapid deterioration in patient health. Herein, we aimed to analyze the precipitating events that cause AD in patients with cirrhosis. Proven bacterial infections and severe alcoholic hepatitis, either alone or in combination, accounted for almost all (96-97%) cases of AD and acute-on-chronic liver failure. Whilst the type of precipitant was not associated with mortality, the number of precipitant(s) was. This study identified precipitants that are significantly associated with a distinct clinical course and prognosis of patients with AD. Specific preventive and therapeutic strategies targeting these events may improve patient outcomes. Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (AD-No ACLF), or with ACLF (AD-ACLF), defined by organ failure(s). Herein, we aimed to analyze and characterize the precipitants leading to both of these AD phenotypes. The multicenter, prospective, observational PREDICT study (NCT03056612) included 1,273 non-electively hospitalized patients with AD (No ACLF = 1,071; ACLF = 202). Medical history, clinical data and laboratory data were collected at enrolment and during 90-day follow-up, with particular attention given to the following characteristics of precipitants: induction of organ dysfunction or failure, systemic inflammation, chronology, intensity, and relationship to outcome. Among various clinical events, 4 distinct events were precipitants consistently related to AD: proven bacterial infections, severe alcoholic hepatitis, gastrointestinal bleeding with shock and toxic encephalopathy. Among patients with precipitants in the AD-No ACLF cohort and the AD-ACLF cohort (38% and 71%, respectively), almost all (96% and 97%, respectively) showed proven bacterial infection and severe alcoholic hepatitis, either alone or in combination with other events. Survival was similar in patients with proven bacterial infections or severe alcoholic hepatitis in both AD phenotypes. The number of precipitants was associated with significantly increased 90-day mortality and was paralleled by increasing levels of surrogates for systemic inflammation. Importantly, adequate first-line antibiotic treatment of proven bacterial infections was associated with a lower ACLF development rate and lower 90-day mortality. This study identified precipitants that are significantly associated with a distinct clinical course and prognosis in patients with AD. Specific preventive and therapeutic strategies targeting these events may improve outcomes in patients with decompensated cirrhosis.