Researchers at EF Clif identify three different clinical courses for the first time, in patients with acute decompensated cirrhosis without acute-on-chronic liver failure (ACLF).
July 14, 2020 – A clinical study led by the European Foundation for the Study of Chronic Liver Failure (EF Clif) in Barcelona has identified three clinical courses in acute decompensated cirrhosis, after hospital admission. Each of them has different pathophysiology and prognostication, which affect the patient’s survival. This finding comes out from the PREDICT Study, a European, prospective and observational project, which aims to identify the clinical course of acute decompensation to foresee the acute-on-chronic liver failure (ACLF) in cirrhosis.
- The results are part of the PREDICT study, aimed to identify predictors and clinical mechanisms to help prevent and treat ACLF.
- The investigators have determined that the development of systemic inflammation is key to the progression of the disease and affects patients with pre-ACLF. Half of them die in three months and seven out of ten in 1 year.
- The study has been led and coordinated by the EF Clif and 136 investigators from 47 centres and institutions in 14 European countries are involved.
Acute decompensation is characterised by acute development of ascites, along with gastrointestinal bleeding, hepatic encephalopathy, infection, or any combination of these factors that may require hospitalisation.
After the first characterisation of ACLF as a distinct syndrome of patients with acute decompensation in the CANONIC study, EF Clif research has identified that acute decompensation in cirrhotic patients without ACLF presents three different clinical courses after hospital admission, and two main pathophysiological mechanisms:
- Pre-ACLF patients develop ACLF within 90 days, have high inflammation and showed the highest mortality rates: 53.7% of them died within 3 months, and 67.4% died before 1 year.
- Patients suffering from unstable decompensated cirrhosis, who had not developed ACLF, show low-grade systemic inflammation, but suffer complications related to severe portal hypertension. In this group, 21% died in the follow-up period and 35.6% died before 1 year.
- Patients with stable decompensated cirrhosis have no severe systemic inflammation or frequent complications related to portal hypertension and showed a mortality rate of only 9.5% after 1 year of participation in the study. This group did not develop ACLF or any episodes of Acute Decompensation in the 3 months of follow-up.
The research has been published in the Journal of Hepatology and has been made possible by the participation of 47 European institutions. According to Prof. Jonel Trebicka from the EF Clif and Principal Investigator of the Study:
The results of this study characterises patients with acute decompensation according to their risk of developing ACLF, the most serious phase of cirrhosis and with a high mortality rate. Early prediction of the patients developing ACLF will result in better management of those patients.
The article, “The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology,” by Jonel Trebicka, Javier Fernandez, Maria Papp, Paolo Caraceni, Wim Laleman, Carmine Gambino, et al. is available open access from the Journal of Hepatology (https://doi.org/10.1016/j.jhep.2020.06.013).
For more information, please contact:
Joël Walicki, PhD
Head of Publications
European Association for the Study of the Liver
About the PREDICT Study
The PREDICT study was designed to prospectively observe patients with acute decompensation at risk of developing ACLF, over a three-month period and to discover predictors and clinical, laboratory, and physiological mechanisms (using prospective auxiliary studies) involved in the development and clinical course of ACLF, which could help prevent and treat this condition.
A project involving 47 organisations and institutions from 14 European countries
The team that works on this study, led by EF Clif, is composed of 136 researchers from various European centres and agencies.
About decompensated cirrhosis and the ACLF
Acute-on-chronic liver failure (ACLF) represents the most severe phase of cirrhosis, characterised by intense systemic inflammation in which patients develop failure of different organs or systems. ACLF is the leading cause of death in the cirrhotic patient and has a large socioeconomic impact, due to the high volume of health resources required for treatment and the non-life disability. The syndrome was first described in 2013 by the same authors of the PREDICT in the CANONIC Study (Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, et al. “Acute-on chronic liver failure is a distinct syndrome that develops in patients with Acute Decompensation of cirrhosis”. Gastroenterology 2013;144). It is currently understood that mortality is due to decompensated cirrhosis, characterized by the appearance of complications such as ascites, digestive bleeding, and disorders of brain function that can reach liver coma and that usually progresses to ACLF.
Recent research led by EASL Clif Consortium has shown that ACLF is a highly complex disorder, which occurs in patients with cirrhosis in which, in addition to the liver, cardiovascular, renal, cerebral, pulmonary, intestinal, adrenal and immune system function may fail. It is therefore a special form of multi-organ failure.
The chance of survival after the onset of the syndrome is low, as it is associated with high short-term morbidity (30% at 28 days) and its only treatment today is liver transplantation.
Notes for editors
About the EF Clif
The European Foundation for the Study of Chronic Liver Failure (EF Clif) is a private, non-profit Foundation whose mission is to promote study and research on Acute-on-Chronic Liver Failure and thus, contribute to improving both the quality of life and survival of patients with liver cirrhosis.
The EF Clif was created in 2015 to support the research work carried out by the EASL Clif Consortium, a research network of more than 100 European University Hospitals and 200 clinical investigators. In 2013, the Consortium described a new syndrome: Acute-on-Chronic Liver Failure (ACLF), which is the most common cause of death in cirrhosis.
Currently, the research activity of the EF Clif is fostered through two chairs: the EASL Clif Chair, to promote observational, pathophysiological and therapeutic studies through the EASL-Clif Consortium’s hospital network; and the Grifols Chair, which promotes the development of translational research projects with the creation of a network of centres across Europe: The European Network for Translational Research in Chronic Liver Failure (ENTR-CLIF).
About the Journal of Hepatology
The Journal of Hepatology is the official journal of the European Association for the Study of the Liver (EASL). It publishes original papers, reviews, case reports, and letters to the Editor concerned with clinical and basic research in the field of hepatology. www.journal-of-hepatology.eu