Jonel Trebicka1, Javier Fernandez2, Maria Papp3, Paolo Caraceni4, Wim Laleman5, Carmine Gambino6, Ilaria Giovo7, Frank Erhard Uschner8, Cesar Jimenez9, Rajeshwar Mookerjee10, Thierry Gustot11, Agustin Albillos12, Rafael Bañares13, Martin Janicko14, Christian Steib15, Thomas Reiberger16, Juan Acevedo17, Pietro Gatti18, William Bernal19, Stefan Zeuzem8, Alexander Zipprich20, Salvatore Piano6, Thomas Berg21, Tony Bruns22, Flemming Bendtsen23, Minneke Coenraad24, Manuela Merli25, Rudolf Stauber26, Heinz Zoller27, José Presa Ramos28, Cristina Solè29, Germán Soriano30, Andrea de Gottardi31, Henning Gronbaek32, Faouzi Saliba33, Christian Trautwein34, Osman Cavit Özdogan35, Sven Francque36, Stephen Ryder37, Pierre Nahon38, Manuel Romero-Gomez39, Hans Van Vlierberghe40, Claire Francoz41, Michael Manns42, Elisabet Garcia43, Manuel Tufoni4, Alex Amoros43, Marco Pavesi43, Cristina Sanchez43, Anna Curto43, Carla Pitarch43, Antonella Putignano11, Esau Moreno43, Debbie Shawcross19, Ferran Aguilar43, Joan Clària2, Paola Ponzo7, Christian Jansen44, Zsuzsanna Vitalis3, Giacomo Zaccherini4, Boglarka Balogh3, Victor Vargas9, Sara Montagnese6, Carlo Alessandria7, Mauro Bernardi4, Pere Ginès29, Rajiv Jalan45, Richard Moreau46, Paolo Angeli47, Vicente Arroyo43. 1. European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; JW Goethe University Hospital, Frankfurt, Germany. Electronic address: jonel.trebicka@kgu.de. 2. European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; Hospital Clinic, IDIBAPS and CIBEehd, Barcelona, Spain. 3. University of Debrecen, Faculty of Medicine, Institute of Medicine, Department of Gastroenterology, Debrecen, Hungary. 4. University of Bologna, Bologna, Italy. 5. University of Leuven, Leuven, Belgium. 6. Department of Medicine, University of Padova, Padova, Italy. 7. Division of Gastroenterology and Hepatology, Città della Salute e della Scienza Hospital, University of Torino, Torino, Italy. 8. JW Goethe University Hospital, Frankfurt, Germany. 9. Liver Unit, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, CIBEREHD, Barcelona, Spain. 10. UCL Medical School, Royal Free Hospital, London, United Kingdom. 11. Universite Libre de Bruxelles, Bruxelles, Belgium. 12. Department of Gastroenterology, Hospital Universitario Ramón y Cajal, IRYCIS, University of Alcalá, CIBEREHD, Madrid, Spain. 13. Gastroenterology and Hepatology Department, Hospital General Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, CIBERehd, Madrid, Spain. 14. Pavol Jozef Safarik University in Kosice, Kosice, Slovakia. 15. Department of Medicine II, University Hospital Munich, Munich, Germany. 16. Medical University of Vienna, Vienna, Austria. 17. University Hospitals Plymouth NHS Trust, Plymouth, UK. 18. Internal Medicine PO Ostuni, ASL Brindisi, Italy. 19. King's College Hospital, London, United Kingdom. 20. University Hospital Halle-Wittenberg, Halle (Saale), Germany. 21. Division of Hepatology, Department of Medicine II, Leipzig University, Medical Center, Leipzig, Germany. 22. Jena University Hospital, Jena, Germany; Aachen University Hospital, Aachen, Germany. 23. Hvidovre University Hospital, Hvidovre, Denmark. 24. Leiden University Medical Center, Leiden, Netherlands. 25. Department of Translational and Precision Medicine, Universitá Sapienza Roma, Roma, Italy. 26. Medical University of Graz, Graz, Austria. 27. Medical University of Innsbruck, Innsbruck, Austria. 28. CHTMAD Vila Real, Vila Real, Portugal. 29. Hospital Clinic, IDIBAPS and CIBEehd, Barcelona, Spain. 30. Hospital de la Santa Creu i Sant Pau and CIBERehd, Barcelona, Spain. 31. University Clinic of Visceral Surgery and Medicine-Inselspital, Bern and Ente Ospedaliero Cantonale, Universita della Svizzera Italiana, Lugano, Switzerland. 32. Aarhus University Hospital, Aarhus, Denmark. 33. AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Universite Paris Saclay, INSERM Unit 1193, Villejuif, France. 34. Aachen University Hospital, Aachen, Germany. 35. Marmara University, Istanbul, Turkey. 36. University Hospital Antwerp, Antwerpen, Belgium. 37. NIHR Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, United Kingdom. 38. AP-HP, Hôpital Jean Verdier, Service d'Hépatologie, Bondy; Université Paris 13, Sorbonne Paris Cité, "Equipe labellisée Ligue Contre le Cancer", Saint-Denis; Inserm, UMR-1162, "Génomique fonctionnelle des tumeurs solides", Paris, France. 39. Virgen del Rocío University Hospital, Sevilla, Spain. 40. Ghent University Hospital, Ghent, Belgium. 41. APHP, Hôpital Beaujon, Service d'Hépatologie, Clichy, France; Inserm, Université de Paris, Centre de Recherche sur L´Inflammation, Paris, France. 42. Hannover Medical School, Hannover, Germany. 43. European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain. 44. University Hospital Bonn, Bonn, Germany. 45. European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; UCL Medical School, Royal Free Hospital, London, United Kingdom. 46. 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. 47. European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; Department of Medicine, University of Padova, Padova, Italy.
Abstract
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.
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.
Authors: Imke Honerkamp; Lisa Sandmann; Nicolas Richter; Michael P Manns; Torsten Voigtländer; Florian W R Vondran; Thomas von Hahn Journal: J Clin Exp Hepatol Date: 2021-04-02
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