Acute on Chronic Liver Failure (ACLF) is a catastrophic event in patients with cirrhosis that carries high mortality. Immune paresis observed in ACLF predisposes to multiple infections and sepsis remains the most common reason for admission, multi-organ failures and mortality in such patients. Often, there is a significant overlap in systemic inflammatory response due to ACLF per se (sterile inflammation) and due to infections (sepsis) that lead to misuse of broad-spectrum antimicrobials; even in the absence of true sepsis. Moreover, there is a great dilemma in differentiating fungal sepsis from bacterial sepsis. Also, the understanding as to why certain patients develop bacterial and others develop fungal infections remains uncertain. Current diagnostics for sepsis relies on cultures (yield: 50% in bacterial and 20-30% in fungal infections) and biomarkers that lack sensitivity, negative predictive value and are often delayed in patients with ACLF. Early diagnosis and adequate treatment of sepsis remain an unmet goal in these patients

A novel technique of untargeted proteomics with a high throughput strategy of liquid chromatography and mass spectrometry (LC/MS) can identify whole proteome and the final effectors in any biological system. It may help identify unique protein signatures as well as pathways associated with a disease or condition. In this project, we aim to elucidate differences in plasma proteomics and clinical profile in ACLF patients with and without sepsis (bacterial/fungal) and find associations with the final outcomes. In addition, we will ascertain the pathophysiology of sepsis in ACLF using this approach.