Serum microRNA-122 kinetics in patients with chronic hepatitis C virus infection during antiviral therapy.

The levels of the liver-specific microRNA-122 (miR-122) circulating extracellularly in the blood have been shown to be increased upon liver damage. However, it is unknown if the levels of serum miR-122 are altered during antiviral therapy and reflect the therapeutic success. Here, we investigated miR-122 serum levels in patients with chronic hepatitis C virus (HCV) genotype 1 infection during antiviral therapy with pegylated interferon and ribavirin. Therefore, sera from 60 patients with chronic HCV infection genotype 1 showing sustained virological response (SVR), non-response or relapse to therapy obtained at baseline, 4, 12, 24 weeks, end of treatment and follow-up were analysed retrospectively for miR-122 content by quantitative real-time reverse transcription PCR. The time courses of miR-122 were correlated with HCV RNA as well as standard liver parameters. We found that while there was no relation between serum miR-122 and HCV RNA levels at baseline, the decline in HCV RNA upon beginning of the therapy closely correlated with the reduction of serum miR-122 in the three different patient groups. Moreover, the serum miR-122 level correlated well with alanine aminotransaminase, a marker of ongoing liver damage. At follow-up serum miR-122 levels remained low in SVR, but increased to baseline levels in patients not responding or showing relapse to therapy. In contrast, the serum concentration of the ubiquitously expressed miR-16 did not change during therapy. We conclude that the serum level of miR-122 well reflects the success of interferon/ribavirin therapy in patients with chronic HCV infection.