ANALYSIS OF THE EXPRESSION LEVEL OF MICRORNA-29A IN PATIENTS WITH DIFFERENT CLINICAL VARIANTS OF CHRONIC HCV-INFECTION

Abstract

The purpose of the work was to analyze the baseline level of microRNA-29a expression in patients with chronic viral hepatitis C with genotype 1 of HCV, depending on the degree of liver fibrosis, the presence of cirrhosis, viral load of HCV, the duration of the disease, and other factors.

Patients and methods: The study examined 74 patients with genotype 1 of chronic HCV infection with a mean age of (47.5±1.4) years. The control group consisted of 11 healthy individuals with negative markers for viral hepatitis, mean age (38.5±5.5) years. According to the degree of fibrosis on the METAVIR scale, patients were distributed as follows, number (%): F1 – 25 (33.8), F2 – 21 (28.4), F3 – 11 (14.9), F4 – 17 (22.9). Moreover, among patients with stage F4 fibrosis, only 10 (58.8 %) patients had clinical signs of liver cirrhosis and stage A liver cirrhosis according to the Child-Pugh classification. The expression level of microRNA-29a (synonyms: miR-29a, hsa-miRNA-29a) was determined by a two-stage study according to the manufacturer’s protocol based on the Department of General and Molecular Pathophysiology of the Institute of Physiology, O.O. Bohomolets of the National Academy of Sciences of Ukraine, where after isolation of total RNA from blood plasma, reverse transcription was performed by quantitative real-time PCR using TaqMan® microRNA analysis (Applied Biosystems, USA). Statistical processing and analysis of data were performed using the software product Statistica v.6.1®.

Results and conclusions. The results of the study showed that aberrant hyperexpression of microRNA-29a was detected in patients with chronic viral hepatitis C compared to healthy individuals: the median level of miR-29a expression in all patients was 20.6 times higher than in the group of healthy individuals and Log10 miR-29a in 4.9 times higher, respectively (p<0.001, U). We have not found significant difference expression level of microRNA-29a in patients according to gender (p=0.940), age (p=0.473), duration of the disease from the time of detection of HCV (p=0.771) and viral load HCV (p=0,505). A significant difference (p=0.002, H) in the expression level of microRNA-29a between patients with chronic HCV infection with varying degrees of fibrosis and in the control group: F0-F1 (p<0.001), F0-F2 (p=0.007), F0-F3 (p<0.001), F0-F4 (p=0.027). The mean level of miR-29 expression in patients can significantly (p<0.001) exclude the initial stages of liver fibrosis in patients with chronic HCV infection and become an additional highly informative noninvasive biomarker in differentiating between early stages of liver fibrosis and advanced liver fibrosis in patients with chronic viral hepatitis C. The level of miRNA-29a expression allows to differentiate the progression of liver fibrosis and cirrhosis in patients and allows to quickly and clearly separate patients with cirrhosis of class A liver according to Child-Pugh classification (p=0.025, H) for further effective management and appropriate antiviral therapy regimens.