ABSTRACT
BACKGROUND: Macrophage activation plays a central role in hepatic and systemic inflammation and is involved in the pathogenesis of acute-on-chronic liver failure (ACLF). AIMS: This study aimed to investigate neopterin levels in patients admitted for acute decompensation (AD) of cirrhosis, evaluating its relationship with ACLF and prognosis. METHODS: This prospective cohort study included 205 adult subjects hospitalized for AD of cirrhosis. Twenty-one healthy subjects and 89 patients with stable cirrhosis were evaluated as controls. RESULTS: Circulating neopterin was higher in AD as compared to stable cirrhosis and healthy controls (p<0.001). ACLF was independently associated with higher neopterin levels (OR 1.015, 95% CI 1.002-1.028, pâ¯=â¯0.025). In the multivariate Cox regression analysis, neopterin levels (HRâ¯=â¯1.002, IC 95% 1.000-1.004, pâ¯=â¯0.041), Child-Pugh class C, and ACLF were predictors of 30-day survival. Among patients with ACLF, the Kaplan-Meier survival probability was 71.4% in those with neopterin levels < 25 nmol/L and 31.0% if neopterin ≥ 25 nmol/L (p<0.001). CONCLUSIONS: Higher circulating neopterin was associated with ACLF in patients hospitalized for AD of cirrhosis. Neopterin levels were also independently predictors of high short-term mortality, especially among patients with ACLF, and could represent a useful biomarker of macrophage activation in clinical practice.
Subject(s)
Acute-On-Chronic Liver Failure/mortality , Liver Cirrhosis/mortality , Neopterin/blood , Acute-On-Chronic Liver Failure/blood , Acute-On-Chronic Liver Failure/diagnosis , Adult , Aged , Biomarkers/blood , Brazil/epidemiology , Female , Humans , Liver Cirrhosis/complications , Macrophage Activation , Male , Middle Aged , Organ Dysfunction Scores , Prognosis , Prospective Studies , ROC Curve , Survival AnalysisABSTRACT
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 twenty-seven 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.
Subject(s)
Acute-On-Chronic Liver Failure/mortality , Biomarkers/blood , Liver Cirrhosis/mortality , MicroRNAs/genetics , Acute-On-Chronic Liver Failure/blood , Acute-On-Chronic Liver Failure/genetics , Acute-On-Chronic Liver Failure/pathology , Case-Control Studies , Female , Humans , Liver Cirrhosis/blood , Liver Cirrhosis/genetics , Liver Cirrhosis/pathology , Male , Middle Aged , Organ Dysfunction Scores , Prognosis , ROC Curve , Severity of Illness Index , Survival RateABSTRACT
INTRODUCTION: Adiponectin and resistin levels are increased in patients with cirrhosis, but it prognostic significance is unknown. We sought to investigate the factors associated with adiponectin and resistin levels and its clinical significance in patients with cirrhosis. MATERIALS AND METHODS: This was a prospective cohort study that included 122 subjects with cirrhosis who attended an outpatient clinic and were initially evaluated in 2012. Serum adiponectin and resistin levels were measured in samples collected in 2012 (adiponectin and resistin) and 2014 (adiponectin). Thirty healthy subjects served as a control group. RESULTS: Higher adiponectin (21.59 µ g/mL vs. 12.52 µg/mL, P < 0.001) and resistin levels (3.83 ng/mL vs. 2.66 ng/mL, P < 0.001) were observed among patients with cirrhosis compared to controls. Patients classified as Child-Pugh B/C had higher adiponectin levels in relation to Child-Pugh A patients. At second measurement, adiponectin levels increased significantly in non-transplant patients and decreased in liver transplant recipients. Univariate Cox analysis showed that among patients with alcoholic liver disease, adiponectin levels were associated with lower transplant-free survival (HR = 1.034, 95% CI 1.006 - 1.062, P = 0.016). The transplant-free survival was significantly lower among patients with alcoholic liver disease and adiponectin ≥ 17 µg/mL (26.55 months, 95% CI 21.40-31.70) as compared to those with levels < 17 µg/mL (33.76 months, 95% CI 30.70-36.82) (P = 0.045). No relationship was found between the levels of resistin and survival. CONCLUSION: Adiponectin but not resistin levels were associated with intensity of liver dysfunction and worse prognosis in patients with alcoholic liver disease, suggesting a potential as a prognostic biomarker.
