Evaluation of MicroRNA-122 as a Biomarker for Chronic Hepatitis C Infection and as a Predictor for Treatment Response to Direct-Acting Antivirals

Abstract

Background: Treatment response to antiviral drugs is a challenging issue in patients with chronic hepatitis C virus (HCV) infection. Although microRNA-122 represents the majority of the microRNA content in hepatic tissues, few studies have evaluated its role in the treatment response, so we aimed to study its role in chronic HCV patients and in predicting the treatment response to direct-acting antivirals (DAAs). Methods: The study included 125 chronic HCV patients (89 naïve and 36 with a prior failed peginterferon/ribavirin response) and 50 apparently healthy subjects. Complete blood count, liver function, α-fetoprotein, lipid profiles, serum creatinine, abdominal ultrasound, and FibroScan ® were assessed. Viral markers, HCV antibodies, and hepatitis B surface antigen were measured by enzyme-linked fluorescent immunoassay, with quantitative estimation of HCV RNA and microRNA-122 levels by real-time PCR. Results: The microRNA-122 level in HCV patients (those with a sustained virologic response 12 weeks after finishing therapy [SVR12] and non-responders) was significantly increased compared with controls and expressed more in non-responders versus SVR12 (p=0.042). ROC curve analysis of microRNA-122 for differentiating HCV patients from healthy controls revealed that a cutoff point of >1.45 had a sensitivity of 67.20%, specificity of 94.0%, AUC=0.861, and p<0.001; and for predicting response to treatment a cutoff point ≤5.66 could significantly (p=0.022) predict the occurrence of SVR, with a sensitivity of 60.34%, specificity of 66.67%, and AUC=0.729. Logistic regression analysis showed significant values for microRNA-122 in multivariate and univariate analysis for the prediction of response to DAAs. Conclusion: The results demonstrated the possible function of microRNA-122 as an indicative tool for distinguishing chronic HCV patients from controls and in the assessment of the therapeutic reaction to DAAs.

Impact of long-term eradication of chronic Hepatitis C infection using the direct-acting antiviral treatment on liver fibrosis parameters in Egyptian patients

“…In this work we noticed that obtaining SVR12 was linked to considerable increase in PLT count, which begins at the end of treatment and lasts for up to 12 months. Come online with our findings Elabd et al has reported significant elevation of platelet count after achieving HCV eradication by DAAs 16 . Additionally, Sayyar et al has concluded that PLT improvement following HCV eradication is most likely due to viral eradication and should not be used or construed as a measure of liver fibrosis or portal hypertension improvement only 17 .…”

Hepatitis C Virus-Lipid Interplay: Pathogenesis and Clinical Impact

“…The 5 UTR IRES is responsible for initiation of HCV viral RNA translation by facilitating its binding to the ribosomal subunit. The microRNA-122 is a liver-specific human microRNA which has an important role in HCV viral replication inside the liver cell [42,43]. Interestingly, binding of microRNA-122 to viral RNA results in upregulation of both HCV RNA and genes that are related to plasma cholesterol and hepatic fatty-acid metabolism [44,45].…”

Oncogenic viruses and host lipid metabolism: a new perspective

“…With the release of the HCV genome into the cytosol, HCV interacts with different lipid-associated factors to promote viral replication, assembly and release. As a liver-specific miRNA, miRNA-122 plays an important role in HCV replication [62]. The binding of miRNA-122 to viral RNA leads to the upregulation of genes involved in lipid metabolism [63].…”