Abstract
MicroRNAs (miRNAs) are small, non-coding RNAs that regulate a variety of biological processes. Recently, human liver-specific miRNA miR-122 has been reported to facilitate hepatitis C virus (HCV) replication in liver cells. HCV is one of the leading causes of liver diseases worldwide. In Pakistan, the estimated prevalence is up to 10%. Here, we report hepatic and serum miR-122 expression profiling from paired liver and serum samples from treatment-naive chronic hepatitis C (CHC) patients and controls. We aimed to elucidate the biomarker potential of serum miR-122 for monitoring disease progression and predicting end treatment response (ETR). Hepatic miR-122 levels were significantly down-regulated in CHC patients. A significant inverse correlation was observed between hepatic and serum miR-122 levels, indicating that serum miR-122 levels reflect HCV-associated disease progression. Both hepatic and serum miR-122 were significantly correlated (P < 0.05) with several clinicopathological features of CHC. Receiver operator curve analysis showed that serum miR-122 had superior discriminatory ability even in patients with normal alanine transaminase levels. Multivariate logistic regression analysis highlighted pre-treatment serum miR-122 levels as independent predictors of ETR. In conclusion, serum miR-122 holds the potential to serve as a promising biomarker of disease progression and ETR in CHC patients.
Highlights
To date, interferon has been considered as the first line of defence against Hepatitis C virus (HCV) infections
In order to investigate if the expression of miR-122 is altered in the liver tissues of CHC patients, miR-122 levels in control and CHC liver tissue samples were measured via real-time quantitative PCR (RT-qPCR)
Hepatic miR-122 levels were significantly different between the normal (P = 1.65 × 10−4) and elevated (P = 8.77 × 10−11) alanine transaminase (ALT) groups of CHC patients compared with those of controls
Summary
Interferon has been considered as the first line of defence against HCV infections. Prediction of the end treatment response (ETR) before the initiation of treatment is a crucial factor that could help in designing better therapeutic strategies and to overcome the undesired socio-economic burden and adverse side effects of PEG-IFN/RBV treatment In this regard, several host and viral factors have been proposed as pre-treatment predictive biomarkers, the most notable of which is interleukin 28B (IL-28B). In addition to the tissue-specific origin and expression of several miRNAs, it has recently been shown that miRNAs can be detected in various body fluids such as serum, plasma and urine[22] In these samples, they exhibit stable expression patterns and are resistant to multiple freeze-thaw cycles and other conditions that can degrade other types of RNA22. We have assessed the potential associations of miR-122 expression levels with the clinicopathological features and outcomes of PEG-INF/RBV therapy in HCV genotype 3 CHC patients
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