Jonel Trebicka1, Javier Fernandez2, Maria Papp3, Paolo Caraceni4, Wim Laleman5, Carmine Gambino6, Ilaria Giovo7, Frank Erhard Uschner8, Christian Jansen9, Cesar Jimenez10, Rajeshwar Mookerjee11, Thierry Gustot12, Agustin Albillos13, Rafael Bañares14, Peter Jarcuska15, Christian Steib16, Thomas Reiberger17, Juan Acevedo18, Pietro Gatti19, Debbie L Shawcross20, Stefan Zeuzem8, Alexander Zipprich21, Salvatore Piano6, Thomas Berg22, Tony Bruns23, Karen Vagner Danielsen24, Minneke Coenraad25, Manuela Merli26, Rudolf Stauber27, Heinz Zoller28, José Presa Ramos29, Cristina Solé30, Germán Soriano31, Andrea de Gottardi32, Henning Gronbaek33, Faouzi Saliba34, Christian Trautwein35, Haluk Tarik Kani36, Sven Francque37, Stephen Ryder38, Pierre Nahon39, Manuel Romero-Gomez40, Hans Van Vlierberghe41, Claire Francoz42, Michael Manns43, Elisabet Garcia-Lopez44, Manuel Tufoni4, Alex Amoros44, Marco Pavesi44, Cristina Sanchez44, Michael Praktiknjo9, Anna Curto44, Carla Pitarch44, Antonella Putignano12, Esau Moreno44, William Bernal20, Ferran Aguilar44, Joan Clària2, Paola Ponzo7, Zsuzsanna Vitalis3, Giacomo Zaccherini4, Boglarka Balogh3, Alexander Gerbes16, Victor Vargas10, Carlo Alessandria7, Mauro Bernardi4, Pere Ginès30, Richard Moreau45, Paolo Angeli46, Rajiv Jalan47, Vicente Arroyo44. 1. European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; Department of Internal Medicine I, Goethe University Frankfurt, Frankfurt, Germany. Electronic address: jonel.trebicka@kgu.de. 2. European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; Hospital Clinic of Barcelona, University of Barcelona, CIBEReHD, IDIBAPS, Barcelona, Spain. 3. University of Debrecen, Faculty of Medicine, Institute of Medicine, Department of Gastroenterology, Debrecen, Hungary. 4. University of Bologna, Bologna, Italy. 5. Department of Gastroenterology and Hepatology, Section of Liver and Biliopancreatic disorders, University of Leuven, Leuven, Belgium. 6. University of Padova, Padova, Italy. 7. A.O.U. Città della Salute e della Scienza Torino, Torino, Italy. 8. Department of Internal Medicine I, Goethe University Frankfurt, Frankfurt, Germany. 9. Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany. 10. Liver Unit, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, CIBEREHD, Barcelona, Spain. 11. UCL Medical School,Royal Free Hospital, London, UK. 12. C.U.B. Erasme, Bruxelles, Belgium. 13. Department of Gastroenterology, Hospital Universitario Ramón y Cajal, IRYCIS, University of Alcalá, CIBEREHD, Madrid, Spain. 14. Hospital General Universitario Gregorio Marañón. Facultad de Medicina (Universidad Complutense of Madrid), CIBERehd, Madrid, Spain. 15. Pavol Jozef Safarik University in Kosice, Kosice, Slovakia. 16. Department of Medicine II, Liver Centre Munich, University Hospital, LMU, Munich, Germany. 17. Medical University of Vienna, Vienna, Austria. 18. University Hospitals Plymouth NHS Trust, Plymouth, UK. 19. Internal Medicine PO Ostuni, ASL Brindisi, Italy. 20. King's College Hospital, London, UK. 21. University Hospital Halle-Wittenberg, Halle(Saale), Germany. 22. Division of Hepatology, Department of Medicine II, Leipzig University, Medical Center, Leipzig, Germany. 23. Jena University Hospital, Jena, Germany; Aachen University Hospital, Aachen, Germany. 24. Gastrounit, Medical Section, Hvidovre Hospital and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. 25. Leiden University Medical Center, Leiden, The Netherlands. 26. Universitá Sapienza Roma, Roma, Italy. 27. Medical University of Graz, Graz, Austria. 28. Medical University of Innsbruck, Innsbruck, Austria. 29. CHTMAD Vila Real-Blueclinical, Vila Real, Portugal. 30. Hospital Clinic of Barcelona, University of Barcelona, CIBEReHD, IDIBAPS, Barcelona, Spain. 31. Hospital de la Santa Creu i Sant Pau and CIBERehd, Barcelona, Spain. 32. University Clinic of Visceral Surgery and Medicine-Inselspital, Bern and Ente Ospedaliero Cantonale, Universita della Svizzera Italiana, Lugano, Switzerland. 33. Aarhus University Hospital, Aarhus, Denmark. 34. AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Universite Paris Saclay, INSERM Unit 1193, Villejuif, France. 35. Aachen University Hospital, Aachen, Germany. 36. Marmara University, Kadiköy, Turkey. 37. University Hospital Antwerp, Antwerp, Belgium. 38. NIHR Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK. 39. AP-HP, Hôpital Jean Verdier, Service d'Hépatologie, Bondy, France; Université Paris 13, Sorbonne Paris Cité, "Equipe labellisée Ligue Contre le Cancer", Saint-Denis, France; Inserm, UMR-1162, "Génomique fonctionnelle des tumeurs solides", Paris, France. 40. Virgen del Rocío University Hospital, Sevilla, Spain. 41. Ghent University Hospital, Ghent, Belgium. 42. APHP, Hôpital Beaujon, Service d'Hépatologie, Clichy, France; Inserm, Université de Paris, Centre de Recherche sur L´Inflammation, Paris, France. 43. Hannover Medical School, Hannover, Germany. 44. European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain. 45. European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; APHP, Hôpital Beaujon, Service d'Hépatologie, Clichy, France; Inserm, Université de Paris, Centre de Recherche sur L´Inflammation, Paris, France. 46. European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; University of Padova, Padova, Italy. 47. European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; UCL Medical School,Royal Free Hospital, London, UK.
Abstract
BACKGROUND & AIMS: 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. 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 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. 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.
BACKGROUND & AIMS: 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. 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 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. 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.
Authors: Johannes Chang; Avend Bamarni; Nina Böhling; Xin Zhou; Leah-Marie Klein; Jonathan Meinke; Georg Daniel Duerr; Philipp Lingohr; Sven Wehner; Maximilian J Brol; Jürgen K Rockstroh; Jörg C Kalff; Steffen Manekeller; Carsten Meyer; Ulrich Spengler; Christian Jansen; Vicente Arroyo; Christian P Strassburg; Jonel Trebicka; Michael Praktiknjo Journal: Hepatol Commun Date: 2021-03-26