found despite strongly elevated ALT levels in these patients. In our study, the liver-specific microRNA miR-122 was upregulated in HCV-4 patients compared with normal controls. miR-122 PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19762596 is known to be a positive cofactor in the HCV replication cycle and serves as a biomarker for hepatic injury. miR-122 facilitates the replication of HCV in both host hepatic cells and non-hepatic cells. However, the mechanism by which miR-122 regulates HCV is not fully understood. miR-122 does not directly affect HCV RNA synthesis in cells or in isolated replication complexes. Vorapaxar site Previous work has shown that miR-122 binding to the HCV 5’UTR stimulates HCV internal ribosome entry site -driven translation. Recently, miR-122 binding was shown to stabilise HCV RNA by protecting it from degradation by the 5′-3′ exonuclease Xrn1, and it was proposed that previous observations of the activation of translation by miR-122 could instead be explained by RNA stabilisation. The profound upregulation of miR-221 in HCV-4 patients could be an indicator of the increased susceptibility of patients to hepatocellular carcinoma, because this miRNA has been implicated as a contributor to liver tumourigenesis. Indeed, miR-221 has been proposed as a potential target for therapeutic intervention in HCC and fulminant liver failure. It is important to note that miR-221 up-regulation has commonly been associated with advanced tumour stages, lower survival rates, and higher recurrence rates in human HCC. Data obtained from this study showed that patients with SVR following pegIFN/RBV therapy had significantly higher pretreatment serum miR-21 and miR-122 levels than NR patients. The same observation concerning miR-122 was reported by and verified by, who revealed that HCV-infected patients who did not respond to therapy had significantly lower miR-122 levels compared with responders. A recent study revealed that the mammalian liver can utilise cellular miRNAs, especially miRNA-122, to fight viral infections through the IFN system. In contrast, an in vivo study showed that there was no correlation between 9 / 12 MicroRNAs as Predictor Markers for Response to Treatment in HCV miR-122 expression and the HCV load in chronic hepatitis patients undergoing IFN therapy. Multiple logistic regression analyses revealed that serum miR-21 and miR-122 levels were correlated with log HCV PCR in HCV-4 patients treated with PEG-IFN /RBV. To the best of our knowledge, this is the first report to correlate miR-21 with the response to PEG-IFN/RBV in HCV-4 patients. This finding suggests that higher pretreatment serum miR-21 and miR-122 levels might predict favourable virological responses to PEG-IFN/RBV therapy in patients with HCV-4. To quantify how strongly miR-21 and miR-122 levels predict the PEG-IFN/RBV therapy response in HCV-4 patients, we performed an OR test. The OR test revealed that miR-21 has a higher predictive value than miR-122 in differentiating NR from SVR patients. The diagnostic performance of miR-21, miR-122, and a combination of these markers PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19763404 in differentiating NR from SVR patients was evaluated by ROC curve analysis. The ROC curve of miR-21 reflected a strong separation between NR and SVR patients, with an AUC of 0.88. The ROC curve of miR-122 showed a moderate ability to distinguish between NR and SVR patients, with an AUC of 0.67. In contrast, miR-221 showed a poor ability to distinguish between NR and SVR patients. The combination of miR-21 and miR-122 strongly differentiated betwee