PI: Jonel Trebicka
(University of Bonn, Germany).
Promoter: EF Clif
The recruitment for the PREDICT Study was closed on the 31 of July 2018 and the last patient and last visit was on the 30 of October 2018. Finally, 47 centres included at least one patient. In total, 1,308 patients were recruited, 1,071 of which were admitted for the treatment of an episode of mere-AD and 227 were recruited with ACLF at inclusion. After the cleaning of the database, the first two papers have been prepared in 2019.
The first paper describes the trajectory of acute decompensation of liver cirrhosis and distinguishes three different phenotypes. Three groups of patients were identified: Pre-ACLF patients (n=218), who 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 not developing ACLF and had 21.0% and 35.6% mortality rates. Stable decompensated cirrhosis (SDC) patients (n = 620) who were neither readmitted, nor developed ACLF and showed a 1-year mortality of only 9.5%. The three groups differed significantly in 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 the SDC) and prevalence of surrogates of severe portal hypertension throughout the study (high in UDC versus low in pre-ACLF and SDC). Mere AD is a heterogeneous condition with three different clinical trajectories and two major pathophysiological mechanisms: systemic inflammation and portal hypertension.
The second study describes the role of precipitating events (PE) in the development of ACLF. A clinical event that precipitates the development of ACLF needs to have two properties. On the one hand, ACLF development should be in close chronological relationship with the PE, meaning that the diagnosis of the PE should be done before or at the time of ACLF onset, and ACLF onset should occur during the duration of the PE-effect. On the other hand, the PE should be characterized by a sufficient severity to induce organ dysfunction and/or failure. The most important PE seems to be bacterial infections (BI). BI were considered a potential PE for ACLF if they were diagnosed prior ACLF onset but resolved within the 48 hours timeframe before diagnosis of the syndrome or were detected at ACLF onset. BI occurring between day 1 and day 10 after the diagnosis of ACLF were considered as complications of ACLF and BI that resolved more than 48 hours before the onset of ACLF were considered unrelated to ACLF. Similarly, the criteria for acute alcoholic liver injury, gastrointestinal bleeding and other PEs were defined. The analysis is still work in progress.
Overall, PREDICT Study was another example of successful collaboration within the European Academic centers and underlines the importance of the disease. It is believed that this study will uncover major parts of currently unknown pathogenesis of development of ACLF and deliver important insight in potential therapeutic approaches of this disease.