Early diagnosis of cirrhosis and hepatocellular carcinoma (HCC) due to chronic Hepatitis\nC (CHC) remain clinical priorities. In this pilot study, we assessed serum microRNA (miRNA)\nexpression to distinguish cirrhosis and HCC, alone and in combination with the aminotransferase-toplatelet\nratio (APRI), Fibrosis 4 (FIB-4), and alpha-fetoprotein (AFP). Sixty CHC patients were\nsubdivided into 3 cohorts: Mild disease (fibrosis stage F0-2; n = 20); cirrhosis (n = 20); and\ncirrhosis with HCC (n = 20). Circulating miRNA signatures were determined using a liver-specific\nreal-time quantitative reverse transcription PCR (qRT-PCR) microarray assessing 372 miRNAs\nsimultaneously. Differentially-expressed miRNA candidates were independently validated using\nqRT-PCR. Serum miRNA-409-3p was increased in cirrhosis versus mild disease. In HCC versus\ncirrhosis, miRNA-486-5p was increased, whereas miRNA-122-5p and miRNA-151a-5p were decreased.\nA logistic regression model-generated panel, consisting of miRNA-122-5p + miRNA-409-3p,\ndistinguished cirrhosis from mild disease (area under the curve, AUC = 0.80; sensitivity = 85%,\nspecificity = 70%; p < 0.001). When combined with FIB-4 or APRI, performance was improved\nwith AUC = 0.89 (p < 0.001) and 0.87 (p < 0.001), respectively. A panel consisting of miRNA-122-5p\n+ miRNA-486-5p + miRNA-142-3p distinguished HCC from cirrhosis (AUC = 0.94; sensitivity =\n80%, specificity = 95%; p < 0.001), outperforming AFP (AUC = 0.64, p = 0.065). Serum miRNAs\nare differentially expressed across the spectrum of disease severity in CHC. MicroRNAs have great\npotential as diagnostic biomarkers in CHC, particularly in HCC where they outperform the only\ncurrently-used biomarker, AFP
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