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


Por: Trebicka, J, Fernandez, J, Papp, M, Caraceni, P, Laleman, W, Gambino, C, Giovo, I, Uschner, FE, Jansen, C, Jimenez, C, Mookerjee, R, Gustot, T, Albillos, A, Banares, R, Jarcuska, P, Steib, C, Reiberger, T, Acevedo, J, Gatti, P, Shawcross, DL, Zeuzem, S, Zipprich, A, Piano, S, Berg, T, Bruns, T, Danielsen, KV, Coenraad, M, Merli, M, Stauber, R, Zoller, H, Ramos, JP, Sole, C, Soriano, G, De Gottardi, A, Gronbaek, H, Saliba, F, Trautwein, C, Kani, HT, Francque, S, Ryder, S, Nahon, P, Romero-Gomez, M, Van Vlierberghe, H, Francoz, C, Manns, M, Garcia-Lopez, E, Tufoni, M, Amoros, A, Pavesi, M, Sanchez, C, Praktiknjo, M, Curto, A, Pitarch, C, Putignano, A, Moreno, E, Bernal, W, Aguilar, F, Claria, J, Ponzo, P, Vitalis, Z, Zaccherini, G, Balogh, B, Gerbes, A, Vargas, V, Alessandria, C, Bernardi, M, Gines, P, Moreau, R, Angeli, P, Jalan, R, Arroyo, V, Maschmeier, M, Semela, D, Elkrief, L, Elsharkawy, A, Tornai, T, Tornai, I, Altorjay, I, Antognoli, A, Baldassarre, M, Gagliardi, M, Bertoli, E, Mareso, S, Brocca, A, Campion, D, Saracco, GM, Rizzo, M, Lehmann, J, Pohlmann, A, Brol, MJ, Chang, J, Schierwagen, R, Sola, E, Amari, N, Rodriguez, M, Nevens, F, Clemente, A, Janicko, M, Markwardt, D, Mandorfer, M, Welsch, C, Welzel, TM, Ciraci, E, Patel, V, Ripoll, C, Herber, A, Horn, P, Bendtsen, F, Gluud, LL, Schaapman, J, Riggio, O, Rainer, F, Moritz, JT, Mesquita, M, Alvarado-Tapias, E, Akpata, O, Aamann, L, Samuel, D, Tresson, S, Strnad, P, Amathieu, R, Simon-Talero, M, Smits, F, Van den Ende, N, Martinez, J, Garcia, R, Rupprechter, H, Engelmann, C, Ozdogan, OC

Publicada: 1 may 2021 Ahead of Print: 1 abr 2021
Resumen:
Background & Aims: Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (ADNo 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. Methods: 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. Results: 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 90day 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. Conclusions: 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. Lay summary: Acute 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. (c) 2020 European Association for the Study of the Liver. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Filiaciones:
Trebicka, J:
 European Fdn Study Chron Liver Failure, EF Clif, Travesera Gracia 11,7th Floor, Barcelona 08021, Spain

 Goethe Univ Frankfurt, Dept Internal Med 1, Frankfurt, Germany

 Munster Univ Hosp, Munster, Germany

 Univ Basel, St Gall Cantonal Hosp, Basel, Switzerland

Fernandez, J:
 European Fdn Study Chron Liver Failure, EF Clif, Travesera Gracia 11,7th Floor, Barcelona 08021, Spain

 Univ Barcelona, Hosp Clin Barcelona, IDIBAPS, CIBEReHD, Barcelona, Spain

 Munster Univ Hosp, Munster, Germany

 Univ Birmingham, Birmingham, W Midlands, England

Papp, M:
 Univ Debrecen, Fac Med, Inst Med, Dept Gastroenterol, Debrecen, Hungary

Caraceni, P:
 Univ Bologna, Bologna, Italy

Laleman, W:
 Univ Leuven, Dept Gastroenterol & Hepatol, Sect Liver & Biliopancreat Disorders, Leuven, Belgium

Gambino, C:
 Univ Padua, Padua, Italy

Giovo, I:
 AOU Citta Salute & Sci Torino, Turin, Italy

Uschner, FE:
 Goethe Univ Frankfurt, Dept Internal Med 1, Frankfurt, Germany

 Univ Basel, St Gall Cantonal Hosp, Basel, Switzerland

Jansen, C:
 Univ Hosp Bonn, Dept Internal Med 1, Bonn, Germany

 Hop Univ Geneve, Geneva, Switzerland

Jimenez, C:
 Univ Autonoma Barcelona, Hosp Vall dHebron, Liver Unit, CIBEREHD, Barcelona, Spain

Mookerjee, R:
 Royal Free Hosp, UCL Med Sch, London, England

Gustot, T:
 CUB Erasme, Brussels, Belgium

Albillos, A:
 Univ Alcald, Hosp Univ Ramon y Cajal, Dept Gastroenterol, CIBEREHD, Madrid, Spain

Banares, R:
 Univ Complutense Madrid, CIBERehd, Fac Med, Hosp Gen Univ Gregorio Maranon, Madrid, Spain

Jarcuska, P:
 Pavol Jozef Safarik Univ Kosice, Kosice, Slovakia

Steib, C:
 LMU, Liver Ctr Munich, Dept Med 2, Univ Hosp, Munich, Germany

Reiberger, T:
 Med Univ Vienna, Vienna, Austria

Acevedo, J:
 Univ Hosp Plymouth NHS Trust, Plymouth, Devon, England

Gatti, P:
 ASL Brindisi, Intenal Med PO Ostuni, Brindisi, Italy

Shawcross, DL:
 Kings Coll Hosp London, London, England

Zeuzem, S:
 Goethe Univ Frankfurt, Dept Internal Med 1, Frankfurt, Germany

 Univ Basel, St Gall Cantonal Hosp, Basel, Switzerland

Zipprich, A:
 Univ Hosp Halle Wittenberg, Halle, Germany

Piano, S:
 Univ Padua, Padua, Italy

Berg, T:
 Leipzig Univ Med Ctr, Dept Med 2, Div Hepatol, Leipzig, Germany

Bruns, T:
 Jena Univ Hosp, Jena, Germany

 Univ Copenhagen, Hvidovre Hosp, Gastro Unit, Med Sect, Copenhagen, Denmark

 Univ Copenhagen, Dept Clin Med, Gastro Unit, Med Sect, Copenhagen, Denmark

Danielsen, KV:
 Med Univ Innsbruck, Innsbruck, Austria

Coenraad, M:
 Leiden Univ, Med Ctr, Leiden, Netherlands

Merli, M:
 Univ Sapienza Roma, Rome, Italy

Stauber, R:
 Med Univ Graz, Graz, Austria

Zoller, H:
 Med Univ Innsbruck, Innsbruck, Austria

Ramos, JP:
 CHTMAD Vila Real, Blueclin, Vila Real, Portugal

Sole, C:
 Univ Barcelona, Hosp Clin Barcelona, IDIBAPS, CIBEReHD, Barcelona, Spain

 Univ Birmingham, Birmingham, W Midlands, England

Soriano, G:
 Univ Clin Visceral Surg & Med Inselspital, Univ Svizzera Italiana, Bern & Ente Osped Cantonale, Lugano, Switzerland

De Gottardi, A:
 Hosp La Santa Creu & St Pau, CIBERehd, Barcelona, Spain

Gronbaek, H:
 Aarhus Univ Hosp, Aarhus, Denmark

Saliba, F:
 Univ Paris Saclay, Hop Paul Brousse, AP HP, Ctr Hepatobiliaire,INSERM Unit 1193, Villejuif, France

Trautwein, C:
 Aachen Univ Hosp, Aachen, Germany

Kani, HT:
 Marmara Univ, Kadikoy, Turkey

Francque, S:
 Univ Hosp Antwerp, Antwerp, Belgium

Ryder, S:
 Nottingham Univ Hosp NHS Trust, NIHR Biomed Res Ctr, Nottingham, England

 Univ Nottingham, Nottingham, England

Nahon, P:
 Hop Jean Verdier, AP HP, Serv Hepatol, Bondy, France

 Univ Paris 13, Equipe Labellisee Ligue Canc, Sorbonne Paris Cite, St Denis, France

 INSERM, Genom Fonct Tumeurs Solides, UMR 1162, Paris, France

Romero-Gomez, M:
 Virgen Rocio Univ Hosp, Seville, Spain

Van Vlierberghe, H:
 Ghent Univ Hosp, Ghent, Belgium

Francoz, C:
 Hop Beaujon, AP HP, Serv Hepatol, Clichy, France

 Univ Paris, Ctr Rech Inflammat, INSERM, Paris, France

Manns, M:
 Hannover Med Sch, Hannover, Germany

Garcia-Lopez, E:
 European Fdn Study Chron Liver Failure, EF Clif, Travesera Gracia 11,7th Floor, Barcelona 08021, Spain

 Munster Univ Hosp, Munster, Germany

Tufoni, M:
 Univ Bologna, Bologna, Italy

Amoros, A:
 European Fdn Study Chron Liver Failure, EF Clif, Travesera Gracia 11,7th Floor, Barcelona 08021, Spain

 Munster Univ Hosp, Munster, Germany

Pavesi, M:
 European Fdn Study Chron Liver Failure, EF Clif, Travesera Gracia 11,7th Floor, Barcelona 08021, Spain

 Munster Univ Hosp, Munster, Germany

Sanchez, C:
 European Fdn Study Chron Liver Failure, EF Clif, Travesera Gracia 11,7th Floor, Barcelona 08021, Spain

 Munster Univ Hosp, Munster, Germany

Praktiknjo, M:
 Univ Hosp Bonn, Dept Internal Med 1, Bonn, Germany

 Hop Univ Geneve, Geneva, Switzerland

Curto, A:
 European Fdn Study Chron Liver Failure, EF Clif, Travesera Gracia 11,7th Floor, Barcelona 08021, Spain

 Munster Univ Hosp, Munster, Germany

Pitarch, C:
 European Fdn Study Chron Liver Failure, EF Clif, Travesera Gracia 11,7th Floor, Barcelona 08021, Spain

 Munster Univ Hosp, Munster, Germany

Putignano, A:
 CUB Erasme, Brussels, Belgium

Moreno, E:
 European Fdn Study Chron Liver Failure, EF Clif, Travesera Gracia 11,7th Floor, Barcelona 08021, Spain

 Munster Univ Hosp, Munster, Germany

Bernal, W:
 Kings Coll Hosp London, London, England

Aguilar, F:
 European Fdn Study Chron Liver Failure, EF Clif, Travesera Gracia 11,7th Floor, Barcelona 08021, Spain

 Munster Univ Hosp, Munster, Germany

Claria, J:
 European Fdn Study Chron Liver Failure, EF Clif, Travesera Gracia 11,7th Floor, Barcelona 08021, Spain

 Univ Barcelona, Hosp Clin Barcelona, IDIBAPS, CIBEReHD, Barcelona, Spain

 Munster Univ Hosp, Munster, Germany

 Univ Birmingham, Birmingham, W Midlands, England

Ponzo, P:
 AOU Citta Salute & Sci Torino, Turin, Italy

Vitalis, Z:
 Univ Debrecen, Fac Med, Inst Med, Dept Gastroenterol, Debrecen, Hungary

Zaccherini, G:
 Univ Bologna, Bologna, Italy

Balogh, B:
 Univ Debrecen, Fac Med, Inst Med, Dept Gastroenterol, Debrecen, Hungary

Gerbes, A:
 LMU, Liver Ctr Munich, Dept Med 2, Univ Hosp, Munich, Germany

Vargas, V:
 Univ Autonoma Barcelona, Hosp Vall dHebron, Liver Unit, CIBEREHD, Barcelona, Spain

Alessandria, C:
 AOU Citta Salute & Sci Torino, Turin, Italy

Bernardi, M:
 Univ Bologna, Bologna, Italy

Gines, P:
 Univ Barcelona, Hosp Clin Barcelona, IDIBAPS, CIBEReHD, Barcelona, Spain

 Univ Birmingham, Birmingham, W Midlands, England

Moreau, R:
 European Fdn Study Chron Liver Failure, EF Clif, Travesera Gracia 11,7th Floor, Barcelona 08021, Spain

 Hop Beaujon, AP HP, Serv Hepatol, Clichy, France

 Univ Paris, Ctr Rech Inflammat, INSERM, Paris, France

 Munster Univ Hosp, Munster, Germany

Angeli, P:
 European Fdn Study Chron Liver Failure, EF Clif, Travesera Gracia 11,7th Floor, Barcelona 08021, Spain

 Univ Padua, Padua, Italy

 Munster Univ Hosp, Munster, Germany

Jalan, R:
 European Fdn Study Chron Liver Failure, EF Clif, Travesera Gracia 11,7th Floor, Barcelona 08021, Spain

 Royal Free Hosp, UCL Med Sch, London, England

 Munster Univ Hosp, Munster, Germany

Arroyo, V:
 European Fdn Study Chron Liver Failure, EF Clif, Travesera Gracia 11,7th Floor, Barcelona 08021, Spain

 Munster Univ Hosp, Munster, Germany

Maschmeier, M:
 European Fdn Study Chron Liver Failure, EF Clif, Travesera Gracia 11,7th Floor, Barcelona 08021, Spain

 Munster Univ Hosp, Munster, Germany

Semela, D:
 Goethe Univ Frankfurt, Dept Internal Med 1, Frankfurt, Germany

 Univ Basel, St Gall Cantonal Hosp, Basel, Switzerland

Elkrief, L:
 Univ Hosp Bonn, Dept Internal Med 1, Bonn, Germany

 Hop Univ Geneve, Geneva, Switzerland

Elsharkawy, A:
 Univ Barcelona, Hosp Clin Barcelona, IDIBAPS, CIBEReHD, Barcelona, Spain

 Univ Birmingham, Birmingham, W Midlands, England

Tornai, T:
 Univ Debrecen, Fac Med, Inst Med, Dept Gastroenterol, Debrecen, Hungary

Tornai, I:
 Univ Debrecen, Fac Med, Inst Med, Dept Gastroenterol, Debrecen, Hungary

Altorjay, I:
 Univ Debrecen, Fac Med, Inst Med, Dept Gastroenterol, Debrecen, Hungary

Antognoli, A:
 Univ Bologna, Bologna, Italy

Baldassarre, M:
 Univ Bologna, Bologna, Italy

Gagliardi, M:
 Univ Bologna, Bologna, Italy

Bertoli, E:
 Univ Padua, Padua, Italy

Mareso, S:
 Univ Padua, Padua, Italy

Brocca, A:
 Univ Padua, Padua, Italy

Campion, D:
 AOU Citta Salute & Sci Torino, Turin, Italy

Saracco, GM:
 AOU Citta Salute & Sci Torino, Turin, Italy

Rizzo, M:
 AOU Citta Salute & Sci Torino, Turin, Italy

Lehmann, J:
 Univ Autonoma Barcelona, Hosp Vall dHebron, Liver Unit, CIBEREHD, Barcelona, Spain

Pohlmann, A:
 Univ Autonoma Barcelona, Hosp Vall dHebron, Liver Unit, CIBEREHD, Barcelona, Spain

Brol, MJ:
 Univ Autonoma Barcelona, Hosp Vall dHebron, Liver Unit, CIBEREHD, Barcelona, Spain

Chang, J:
 Univ Autonoma Barcelona, Hosp Vall dHebron, Liver Unit, CIBEREHD, Barcelona, Spain

Schierwagen, R:
 Univ Hosp Plymouth NHS Trust, Plymouth, Devon, England

Sola, E:
 Royal Free Hosp, UCL Med Sch, London, England

Amari, N:
 CUB Erasme, Brussels, Belgium

Rodriguez, M:
 Univ Alcald, Hosp Univ Ramon y Cajal, Dept Gastroenterol, CIBEREHD, Madrid, Spain

Nevens, F:
 Univ Leuven, Dept Gastroenterol & Hepatol, Sect Liver & Biliopancreat Disorders, Leuven, Belgium

Clemente, A:
 Univ Complutense Madrid, CIBERehd, Fac Med, Hosp Gen Univ Gregorio Maranon, Madrid, Spain

Janicko, M:
 Pavol Jozef Safarik Univ Kosice, Kosice, Slovakia

Markwardt, D:
 LMU, Liver Ctr Munich, Dept Med 2, Univ Hosp, Munich, Germany

Mandorfer, M:
 Med Univ Vienna, Vienna, Austria

Welsch, C:
 Univ Hosp Plymouth NHS Trust, Plymouth, Devon, England

Welzel, TM:
 Univ Hosp Plymouth NHS Trust, Plymouth, Devon, England

Ciraci, E:
 ASL Brindisi, Intenal Med PO Ostuni, Brindisi, Italy

Patel, V:
 Kings Coll Hosp London, London, England

Ripoll, C:
 Univ Hosp Halle Wittenberg, Halle, Germany

Herber, A:
 Leipzig Univ Med Ctr, Dept Med 2, Div Hepatol, Leipzig, Germany

Horn, P:
 Jena Univ Hosp, Jena, Germany

Bendtsen, F:
 Univ Copenhagen, Hvidovre Hosp, Gastro Unit, Med Sect, Copenhagen, Denmark

 Univ Copenhagen, Dept Clin Med, Gastro Unit, Med Sect, Copenhagen, Denmark

Gluud, LL:
 Univ Copenhagen, Hvidovre Hosp, Gastro Unit, Med Sect, Copenhagen, Denmark

 Univ Copenhagen, Dept Clin Med, Gastro Unit, Med Sect, Copenhagen, Denmark

Schaapman, J:
 Leiden Univ, Med Ctr, Leiden, Netherlands

Riggio, O:
 Univ Sapienza Roma, Rome, Italy

Rainer, F:
 Med Univ Graz, Graz, Austria

Moritz, JT:
 Med Univ Innsbruck, Innsbruck, Austria

Mesquita, M:
 CHTMAD Vila Real, Blueclin, Vila Real, Portugal

Alvarado-Tapias, E:
 Univ Clin Visceral Surg & Med Inselspital, Univ Svizzera Italiana, Bern & Ente Osped Cantonale, Lugano, Switzerland

Akpata, O:
 Hosp La Santa Creu & St Pau, CIBERehd, Barcelona, Spain

Aamann, L:
 Aarhus Univ Hosp, Aarhus, Denmark

Samuel, D:
 Univ Paris Saclay, Hop Paul Brousse, AP HP, Ctr Hepatobiliaire,INSERM Unit 1193, Villejuif, France

Tresson, S:
 Univ Paris Saclay, Hop Paul Brousse, AP HP, Ctr Hepatobiliaire,INSERM Unit 1193, Villejuif, France

Strnad, P:
 Aachen Univ Hosp, Aachen, Germany

Amathieu, R:
 Marmara Univ, Kadikoy, Turkey

Simon-Talero, M:
 Univ Hosp Antwerp, Antwerp, Belgium

Smits, F:
 CUB Erasme, Brussels, Belgium

Van den Ende, N:
 Univ Leuven, Dept Gastroenterol & Hepatol, Sect Liver & Biliopancreat Disorders, Leuven, Belgium

Martinez, J:
 Univ Alcald, Hosp Univ Ramon y Cajal, Dept Gastroenterol, CIBEREHD, Madrid, Spain

Garcia, R:
 Univ Complutense Madrid, CIBERehd, Fac Med, Hosp Gen Univ Gregorio Maranon, Madrid, Spain

Rupprechter, H:
 Med Univ Vienna, Vienna, Austria

Engelmann, C:
 Leipzig Univ Med Ctr, Dept Med 2, Div Hepatol, Leipzig, Germany

Ozdogan, OC:
 Nottingham Univ Hosp NHS Trust, NIHR Biomed Res Ctr, Nottingham, England

 Univ Nottingham, Nottingham, England
ISSN: 01688278
Editorial
ELSEVIER, RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS, Países Bajos
Tipo de documento: Article
Volumen: 74 Número: 5
Páginas: 1097-1108
WOS Id: 000640696100013
ID de PubMed: 33227350
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