THE CANONIC STUDY

Metabolomic score in patients from the CANONIC Study. Validation in patients from the PREDICT Study.

Translational research Richard Moreau (EF Clif. Barcelona, Spain)
Christophe Junot (CEA. Saclay, France)

Promoter: EF Clif
Start date: 01/01/2020
End date: 31/12/2020

Untargeted blood metabolomics performed in 831 patients with acutely decompensated (including 181 with ACLF) revealed a 38-metabolite signature that was distinctive of ACLF versus no ACLF (J Hepatol 2020;72:688-701). The objective of the study was to validate the 38-metabolite signature previously found in the CANONIC Study among 800 patients with acutely decompensated cirrhosis enrolled in the PREDICT study. Within 2020, the analysis of blood metabolomics was completed. The results show that 36 of the 38 metabolites has a discriminative accuracy for distinguishing patients with poor outcomes (development of ACLF, death) from those with better outcomes. A report of the results is under preparation.

Addressing the role of amino acids in systemic inflammatory responses and organ failures in patients with ACLF.

Translational research Richard Moreau (EF Clif. Barcelona, Spain)
Vicente Arroyo (EF Clif. Barcelona, Spain)
Giacomo Zaccherini (University of Bologna. Bologna, Italy; EF Clif (visiting fellow). Barcelona, Spain

Promoter: EF Clif
Start date: 1/01/2020
End date: 23/11/2020

The objective of the study was to reanalyse the metabolome data set obtained, in patients with acutely decompensated cirrhosis enrolled in the CANONIC study, in order to assess the relative contribution of main organ system failures to changes in blood metabolic in samples collected.

The results showed that blood metabolites were mainly composed of amino acids and distributed across 9 distinct modules. ACLF was characterized by increases in the 9 metabolite modules. Increases in a large proportion of metabolites were independently associated with kidney failure; the same true for liver failure. Lesser proportions of metabolites were independently associated with the grade of hepatic encephalopathy. The results have been reported in an original article published in Journal of Hepatology (2021; in press).

GWAS analysis in the CANONIC patients. Validation in patients from the PREDICT Study.
Association with metabolomics and with inflammatory markers.

Translational research Joan Clària (Hospital Clínic Barcelona-IDIBAPS; EF Clif. Barcelona, Spain)
Eric Trepo (Hôpital Erasme, Université Libre de Bruxelles. Brussels, Belgium)

Promoter: EF Clif
Start date: 01/01/2019
End date: 30/06/2021

The aim of this study was the identification of genetic variants associated with the progression to ACLF in patients with acutely decompensated cirrhosis. Additionally, this study aimed at identifying genetic variants that might influence the clinical course and severity of advanced liver disease.

The study was initially performed in 829 patients with decompensated cirrhosis recruited in the CANONIC study (a multicentre observational investigation involving 1343 hospitalized patients with cirrhosis from February to September 2011 in 29 liver units within 8 European countries), which were genotyped using the Infinium® Global Screening Array (Illumina, San Diego, CA). To gain power, the study was expanded to include 778 patients with decompensated cirrhosis from the PREDICT study and more than 1000 patients from the ACLARA study, both multicentre observational investigations within European and Latin American countries, respectively. The genotyping for these two additional cohorts is currently ongoing.