Abstract

The authors present the study of the level of expression of miR-196a in 74 patients with chronic viral hepatitis C with the 1st genotype of HCV, based on previous experience in patients with antiviral therapy regimens containing interferon. The patients were divided into two groups, depending on the previous experience of antiviral therapy with circuits containing interferon – 21 patients who failed after antiviral therapy regimens containing interferon (group 1) and the comparison group (group 2) – 53 naive patients. To study the level of expression of miR-196a (miR-196a), a two-stage study according to the manufacturer's protocol was used. First, total RNA was isolated from the plasma by the method of phenol-chloroform extraction. Futher reverse transcription was performed using a kit for reverse transcription of miR TaqMan® (Applied Biosystems, USA), specific loop primers to achieve mature miRNA, snRNA U6 (as an endogenous control gene), and 10 ng of total RNA. Real-time quantitative PCR was performed using TaqMan® miRNA analysis. In order to optimize the prediction of response to antiviral therapy and the use of optimal treatment regimens for problem patients with treatment failure regimens containing interferon, analysis using ROC curves was used. The average level of expression of miR-196a in patients with chronic hepatitis C was evaluated. In the 1st group of patients it was 0.011 (IQR: 0.002; 0.310) and in the comparison group – 0.346 (IQR: 0.054; 1.239) at p=0.012 by U criterion. The conducted ROC analysis showed that the studied miR-196a could differentiate patients with chronic viral hepatitis C with HCV genotype 1, depending on previous experience of antiviral therapy, namely, patients with treatment failure regimens containing interferons and naive. AUC=0.688 (95% CI 0.570-0.791; p=0.017), J=0.40, Se=57.14%, Sp=83.02%. It gives additional opportunities for correction of therapeutic tactics. Therefore, the level of expression of miR-196a (<-1,75) may be an additional biomarker in the pathogenesis of HCV-infection, which can then be used in the monitoring and treatment of patients. Low expression of miR-196a may be the basis for prescribing more effective direct-acting antiviral therapy to patients and will allow personalizing therapeutic tactics in patients with chronic viral hepatitis C.

Highlights

  • The level of expression of miR-196a in patients with chronic viral hepatitis C with the first genotype of hepatitis C virus (HCV) according to previous experience of antiviral therapy

  • The aim of the study was to investigate the level of expression of miR-196a in Ukrainian patients with chronic viral hepatitis C with HCV genotype 1, depending on previous experience of interferoncontaining antiviral therapy to predict the likelihood of an unsuccessful response to antiviral therapy and further assigning optimal therapy regimens to problem patients

  • Following clinical anamnestic analysis, laboratory and instrumental studies, baseline expression of miR-196a was determined in all patients compared to healthy subjects, as reported in our previous publications [3]

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Summary

Introduction

The level of expression of miR-196a in patients with chronic viral hepatitis C with the first genotype of HCV according to previous experience of antiviral therapy. The conducted ROC analysis showed that the studied miR-196a could differentiate patients with chronic viral hepatitis C with HCV genotype 1, depending on previous experience of antiviral therapy, namely, patients with treatment failure regimens containing interferons and naive. Проведений ROC-аналіз показав, що досліджувана мікроРНК-196a може диференціювати пацієнтів з ХВГС з 1-м генотипом HCV, залежно від попереднього досвіду противірусної терапії, а саме, у хворих з невдачами терапії схемами, що містять інтерферон, та наївних пацієнтів - AUC=0,688 (95% CI 0,570–0,791; p=0,017), J=0,40, Se=57,14%, Sp=83,02%, ДЕ=70,08 пов'язаний критерій експресії miR-196a становив ≤0,0178 ум. HCV-infection causes chronic inflammation, and the regulation of inflammation associated with miRNAs promotes the initiation and progression of hepatocellular carcinoma [7]

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