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Observational Study
. 2020 Oct;73(4):842-854.
doi: 10.1016/j.jhep.2020.06.013. Epub 2020 Jul 13.

The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology

Jonel Trebicka  1 , Javier Fernandez  2 , Maria Papp  3 , Paolo Caraceni  4 , Wim Laleman  5 , Carmine Gambino  6 , Ilaria Giovo  7 , Frank Erhard Uschner  8 , Cesar Jimenez  9 , Rajeshwar Mookerjee  10 , Thierry Gustot  11 , Agustin Albillos  12 , Rafael Bañares  13 , Martin Janicko  14 , Christian Steib  15 , Thomas Reiberger  16 , Juan Acevedo  17 , Pietro Gatti  18 , William Bernal  19 , Stefan Zeuzem  8 , Alexander Zipprich  20 , Salvatore Piano  6 , Thomas Berg  21 , Tony Bruns  22 , Flemming Bendtsen  23 , Minneke Coenraad  24 , Manuela Merli  25 , Rudolf Stauber  26 , Heinz Zoller  27 , José Presa Ramos  28 , Cristina Solè  29 , Germán Soriano  30 , Andrea de Gottardi  31 , Henning Gronbaek  32 , Faouzi Saliba  33 , Christian Trautwein  34 , Osman Cavit Özdogan  35 , Sven Francque  36 , Stephen Ryder  37 , Pierre Nahon  38 , Manuel Romero-Gomez  39 , Hans Van Vlierberghe  40 , Claire Francoz  41 , Michael Manns  42 , Elisabet Garcia  43 , Manuel Tufoni  4 , Alex Amoros  43 , Marco Pavesi  43 , Cristina Sanchez  43 , Anna Curto  43 , Carla Pitarch  43 , Antonella Putignano  11 , Esau Moreno  43 , Debbie Shawcross  19 , Ferran Aguilar  43 , Joan Clària  2 , Paola Ponzo  7 , Christian Jansen  44 , Zsuzsanna Vitalis  3 , Giacomo Zaccherini  4 , Boglarka Balogh  3 , Victor Vargas  9 , Sara Montagnese  6 , Carlo Alessandria  7 , Mauro Bernardi  4 , Pere Ginès  29 , Rajiv Jalan  45 , Richard Moreau  46 , Paolo Angeli  47 , Vicente Arroyo  43 ; PREDICT STUDY group of the EASL-CLIF Consortium
Collaborators, Affiliations
Free article
Observational Study

The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology

Jonel Trebicka et al. J Hepatol. 2020 Oct.
Free article

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.

Keywords: Acute complications; Chronic liver disease; Non-elective admission; Outcome; Risk factors.

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Conflict of interest statement

Conflict of interest None of the authors have conflicts of interest for the reported study. Please refer to the accompanying ICMJE disclosure forms for further details.

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