TY - JOUR

T1 - The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology

AU - Trebicka, Jonel

AU - Fernandez, Javier

AU - Papp, Maria

AU - Caraceni, Paolo

AU - Laleman, Wim

AU - Gambino, Carmine

AU - Giovo, Ilaria

AU - Uschner, Frank Erhard

AU - Jimenez, Cesar

AU - Mookerjee, Rajeshwar

AU - Gustot, Thierry

AU - Albillos, Agustin

AU - Bañares, Rafael

AU - Janicko, Martin

AU - Steib, Christian

AU - Reiberger, Thomas

AU - Acevedo, Juan

AU - Gatti, Pietro

AU - Bernal, William

AU - Zeuzem, Stefan

AU - Zipprich, Alexander

AU - Piano, Salvatore

AU - Berg, Thomas

AU - Bruns, Tony

AU - Bendtsen, Flemming

AU - Coenraad, Minneke

AU - Merli, Manuela

AU - Stauber, Rudolf

AU - Zoller, Heinz

AU - Ramos, José Presa

AU - Solè, Cristina

AU - Soriano, Germán

AU - de Gottardi, Andrea

AU - Gronbaek, Henning

AU - Saliba, Faouzi

AU - Trautwein, Christian

AU - Özdogan, Osman Cavit

AU - Francque, Sven

AU - Ryder, Stephen

AU - Nahon, Pierre

AU - Romero-Gomez, Manuel

AU - Van Vlierberghe, Hans

AU - Francoz, Claire

AU - Manns, Michael

AU - Garcia, Elisabet

AU - Tufoni, Manuel

AU - Amoros, Alex

AU - Pavesi, Marco

AU - Danielsen, Karen Vagner

AU - Gluud, Lise Lotte

AU - PREDICT STUDY group of the EASL-CLIF CONSORTIUM

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Acute complications

KW - Chronic liver disease

KW - Non-elective admission

KW - Outcome

KW - Risk factors

U2 - 10.1016/j.jhep.2020.06.013

DO - 10.1016/j.jhep.2020.06.013

M3 - Journal article

C2 - 32673741

AN - SCOPUS:85088972261

VL - 73

SP - 842

EP - 854

JO - Journal of Hepatology, Supplement

JF - Journal of Hepatology, Supplement

SN - 0169-5185

IS - 4

ER -