Acute-on-chronic liver failure (ACLF) is a condition characterized by acute decompensation of cirrhosis, associated with organ failure(s), and high short-term mortality. The microRNAs or miRNAs are small non-coding RNA molecules, stable in circulating samples such as biological fluids, and the difference in expression levels may indicate the presence, absence and/or stage of the disease. We analyzed here the miRNA profiling to identify potential diagnostic or prognostic biomarkers for ACLF. The major miRNAs discovered were validated in a cohort of patients with acute decompensation of cirrhosis grouped in no ACLF or ACLF according to EASL-CLIF definition. Relationship between serum miRNAs and variables associated with liver-damage and survival outcomes were verified to identify possible prognostic markers. Our results showed twenty altered miRNAs between no ACLF and ACLF patients, and twentyseven in patients who died in 30 days compared with who survived. In validation phase, miR-223-3p and miR-25-3p were significantly altered in ACLF patients and in those who died in 30 days. miR-223-3p and miR-25-3p expression were associated with the lowest survival in 30 days. The decrease in miR-223-3p and miR-25-3p expression was associated with the presence of ACLF and poor prognosis. Of these, miR-25-3p was independently related to ACLF and 30-day mortality. The natural history of cirrhosis is usually characterized by a long-standing compensated phase followed by a transition to the decompensated disease, identified by the occurrence of specific complications of cirrhosis, such as ascites, variceal bleeding, and hepatic encephalopathy 1. Patients with both compensated or decompensated cirrhosis are at risk of progression to acute-on-chronic liver failure (ACLF), a condition characterized by an acute deterioration of the liver function and characterized by progression to extrahepatic organ failure and high short-term mortality 2,3. Although a precise definition is still lacking, the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium definition is one of the most validated criteria for ACLF in patients with cirrhosis and it is based on a modified version of SOFA score called CLIF-SOFA 2,4. According to a recently published study 5 , mortality rates in ACLF patients are 25.5% and 40% in 28 and 90 days of admission, respectively. Therefore, searching for new biomarkers associated with the presence of ACLF and prognosis of patients with acute decompensation of cirrhosis may improve clinical decision and help to implement risk-adapted treatment strategies. In recent years, miRNAs have been studied as promising biomarkers for the diagnosis and prognostic in many clinical scenarios 6-8 , including liver diseases 9. The miRNAs are a group of small non-coding RNAs, with approximately 22 nucleotides, which post-transcriptionally regulate gene expression

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BACKGROUND Acute decompensation (AD) of cirrhosis is related to systemic inflammation and elevated circulating cytokines. In this context, biomarkers of inflammation, such as calprotectin, may be of prognostic value. AIM To evaluate serum calprotectin levels in patients hospitalized for complications of cirrhosis. METHODS This is a prospective cohort study that included 200 subjects hospitalized for complications of cirrhosis, 20 outpatients with stable cirrhosis, and 20 healthy controls. Serum calprotectin was measured by enzyme-linked immunosorbant assay. RESULTS Calprotectin levels were higher among groups with cirrhosis when compared to healthy controls. Higher median calprotectin was related to Child-Pugh C, ascites, and hepatic encephalopathy. Higher calprotectin was related to acute-on-chronic liver failure (ACLF) and infection in the bivariate, but not in multivariate analysis. Calprotectin was not associated with survival among patients with ACLF; however, in patients with AD without ACLF, higher calprotectin was associated with a lower 30-d survival, even after adjustment for chronic liver failure-consortium (CLIF-C) AD score. A high-risk group (CLIF-C AD score ≥ 60 and calprotectin ≥ 580 ng/mL) was identified, which had a 30-d survival (27.3%) similar to that of patients with grade 3 ACLF (23.3%). CONCLUSION Serum calprotectin is associated with prognosis in patients with AD without ACLF and may be useful in clinical practice to early identify patients with a very low short-term survival.

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