MicroRNA profiles in serum samples from patients with stable cirrhosis and miRNA-21 as a predictor of transplant-free survival

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Graphical abstractMicroRNAs (miRNAs) have remarkable potential as diagnostic and prognostic markers because of their roles in disease pathogenesis. miRNAs can be released into the bloodstream, where they are sufficiently stable to be detected noninvasively. Here, we prospectively evaluated serum levels of miR-21, miR-34a, miR-122, miR-181b, and miR-885-5p in patients with stable cirrhosis. Total RNA was extracted from the sera of patients with cirrhosis and healthy individuals, and the expression levels of the target miRNAs were analyzed by reverse transcription-quantitative polymerase chain reaction. Serum miRNAs levels were correlated with liver function parameters, etiology, and complications of cirrhosis. Circulating miR-34a, miR-122, and miR-885-5p levels were higher in patients with cirrhosis than in healthy individuals. These miRNAs were positively correlated with alanine aminotransferase and aspartate aminotransferase levels, and the relative expression levels were higher in hepatitis C virus-infected patients and lower in patients with Child-Pugh C cirrhosis. miR-122 and miR-885-5p levels were also positively correlated with γ-glutamyl transpeptidase concentrations. miR-21 was associated with transplant-free survival in univariate Cox regression analysis and remained independently associated with survival after adjustment for age, Child-Pugh classification, Model for End-stage Liver Disease score, and history of previous decompensation in multivariate Cox regression analysis. These data suggested that miR-34a, miR-122, and miR-885-5p levels may be more related to the inflammatory process and ongoing hepatocyte damage in patients with cirrhosis. Moreover, miR-21 levels were independently associated with shorter transplant-free survival and may be used as a prognostic tool in outpatients with stable cirrhosis.

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