BACKGROUND: MicroRNA-122 (miR-122) is an important host factor for hepatitis C 
virus replication. Administration of miravirsen, an anti-miR-122 
oligonucleotide, resulted in a dose dependent and prolonged decrease in HCV RNA 
levels in chronic hepatitis C patients.
AIM: To assess the plasma level of various miRNAs in patients dosed with 
miravirsen.
METHODS: We included 16 of 36 chronic hepatitis C patients who received five 
injections of either 3 mg/kg (n = 4), 5 mg/kg (n = 4), 7 mg/kg (n = 4) 
miravirsen or placebo (n = 4) over a 4-week period in a double-blind, randomised 
phase 2a study. Plasma levels of 179 miRNAs were determined by qPCR and compared 
between patients dosed with miravirsen or placebo.
RESULTS: Median plasma miR-122 level at baseline in patients receiving 
miravirsen was 3.9 × 10(3) compared to 1.3 × 10(4) copies/4 μL in placebo-dosed 
patients (P = 0.68). At week 1, 4, 6 and 10/12, patients dosed with miravirsen 
had respectively a median 72-fold, 174-fold, 1109-fold and 552-fold lower 
expression of miR-122 than at baseline (P = 0.001, as compared to patients 
receiving placebo). At week 4 of dosing, miRNA-profiling demonstrated a 
significant lower expression of miR-210 and miR-532-5p compared to baseline (3.0 
and 4.7-fold lower respectively). However, subsequent longitudinal analysis 
showed no significant differences in miR-210 and miR-532-5p plasma levels 
throughout the study period.
CONCLUSIONS: We demonstrated a substantial and prolonged decrease in plasma 
miR-122 levels in patients dosed with miravirsen. Plasma levels of other miRNAs 
were not significantly affected by antagonising miR-122.