SPP1 as a risk factor for patients with acute on chronic liver failure undergoing liver transplantation

•SPP1 mRNA was upregulated in PBMCs and hepatic CD45+ cells of ACLF patients.•SPP1 level was associated with organ failure and the severity of ACLF.•A higher SPP1 level in ACLF patients prior to LT indicated a poor outcome.•SPP1 enhanced the predictive capacities of existing models for post-LT prognosis. Acute on chronic liver failure (ACLF) is characterized by systemic inflammation and significant mortality, calling for accurate assessment due to the diverse prognosis of liver transplantation (LT). 8 patients with ACLF and 4 normal controls (NC) underwent peripheral blood mononuclear cells (PBMCs) transcriptomics, whereas 9 patients with ACLF and 3 NC had hepatic CD45+ T cells transcriptomics. Thecandidateindicatorfoundinthetranscriptomicswas confirmedbya retrospective cohort (n = 137) and one prospective cohort (n = 68). Transcriptomics revealed significant differentially expression genes (DEGs) and bioprocesses related to the PBMCs and hepatic CD45+ T cells. Secreted phosphoprotein 1 (SPP1) was identified as a potential indicator for ACLF patients receiving LT, which was supported by evidence from the cross-sectional cohorts. As the condition of ACLF got worse, so did SPP1 levels, which were associated with liver failure and coagulation failure. SPP1 levels prior to LT were considerably greater in non-survivors of ACLF within 90 days than that in survivors. In the derivation cohort and validation cohort, ACLF patients with elevated SPP1 levels had significantly shorter cumulative survival durations than those with low SPP1 levels, P = 0.02 and P