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Abstract Hepatitis C virus infection is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. It has been estimated that 180 million people are infected worldwide. MicroRNAs are small non-coding RNAs of 19–24 nucleotides in length that regulate gene expression by posttranscriptional mechanism. MiR-122 expression is enriched in the liver, accounting for approximately 70 % of the total miRNA population in normal adult hepatocytes. It plays a crucial role in the HCV infection. The aim of this study was to determine gene expression of miR-122 in both hepatic tissue and peripheral blood of chronic HCV infected Egyptian patients and to correlate the level of expression with the serum HCV load. All subjects enrolled in the study were recruited from Ain Shams University Specialized Hospital, Transplantation Unit, and the laboratory work was conducted in Clinical Pathology Department, Immunology Unit Ain Shams University Hospital. The study included 20 patients diagnosed as CHC (group I) and 10 healthy controls (group II). group (I) was further subdivided according to the results of the last HCV RTPCR into two groups:- group IA: Including 17 patients with HCV-PCR positive. group IB: Including 3 patients with HCV-PCR negative. All individuals included were subjected to measurement of AST, ALT, ALP, ALB, AFP and HCV load. The study showed high statistical significant difference (P<0.001) between CHC patients and control group regarding ALT, AST, ALP and AFP being higher in the former group. On the other hand, serum level of ALB showed a high statistical significant difference (P<0.001) between both groups being decreased in CHC patients. Similarly, there was statistical significant increase (P<0.05) of serum AST level, and decrease of serum AFP in group IA when compared to group IB. Detection and relative quantification of miR-122 expression levels, was performed on 30 peripheral blood samples using RT- PCR. Regarding miR-122 expression level, a statistically significant difference was found between CHC patients when compared to control group (P <0.001). Similarly, statistical significant difference of both miR- 122 expression levels in the peripheral blood or hepatic tissue being higher in-group IA when compared to group IB (P<0.001). On the other hand, there was no significant difference between group IB and group II as regard peripheral blood miR-122 gene expression. Regarding the correlation between miR-122 expression levels in both peripheral blood and liver tissue and each of ALT and AST, the study showed a significant positive correlation. On the other hand, there was statistical significant negative correlation with AFP level in group I and group IA. In conclusion, our results demonstrated a significantly higher expression of miR-122 in adult Egyptian CHC patients compared to controls and a strong association of miR-122 with hepatocyte necroinflammation markers (AST, ALT) indicating that it may play an important role in activ state of HCV and introduces it as a potential predictor of disease progression. These findings lead us to conclude that HCV infection results in modulation of miR-122 gene expression, a finding that has drawn our attention to the possible role of miR-122 in viral confrontation and clearance. However, the biological functions of these miRNAs require further investigation to elucidate if serum miR-122 may serve as an interesting biomarker for early hepatic inflammation responses or other pathological process in HCV patients. We also conclude that elevated serum miR-122 levels may require further understanding of the role of liver injury and an s yet undetermined additional mechanism of active synthesis of miR-122 that is most evident during chronic HCV infection, and accounts for the high levels of circulating miR-122 observed. Further understanding of miR function may indicate whether induced levels are secondary to an intrinsic hepatocyte response or represent a mechanism unique to HCV. Understanding miR-122 elevations in the hepatitis C setting might lead to new antiviral strategies. |