The DECISION project aims to discover more personalized combinatorial therapies for patients with decompensation of cirrhosis. This will be achieved by using readily available clinical data, prospectively collected in a homogenous manner from large clinical studies, with the corresponding standardized biobank samples that will produce omics data once they are fully analyzed.. DECISION

Intense systemic inflammation is thought to be a driver of the most severe forms of acutely decompensated cirrhosis. Therefore, systemic inflammation may be a target for novel therapeutic approaches among patients with acutely decompensated cirrhosis. Identification of molecular mechanisms underlying systemic inflammation and of circulating immune-cell subsets that are involved in this disorder are of upmost importance. Whole-blood RNA-sequencing data from 1346 patients admitted to the hospital for acutely decompensated cirrhosis without acute-on-chronic liver failure (ACLF) were first used for enrichment analyses. The results showed that activation of major inflammatory pathways (depending on master cytokines IL-6 and TNF-alpha) and downregulation of MYC signaling (which may indicate defective homeostasis of the lymphoid compartment) were markers of the two most severe outcomes (i.e., ACLF [characterized by organ system failures] and death). Deconvolution of whole-blood RNA-seq data are ongoing to decipher any alteration in blood of the myeloid compartment and the lymphoid compartment. Weighted gene co-expression network analysis (WGCNA) will be used to reduce the dimension of whole-blood transcriptome datatype and identify modules of co-expressed genes and their eigengenes, with the perspective of data integration.