Hepatitis C virus (HCV)
infection causes sustained
inflammation and
fibrosis. Several oral direct-acting
antivirals (DAAs) including
ombitasvir/
paritaprevir/
ritonavir (OBV/PTV/r) were recently developed for HCV elimination. The combination of DAAs brought a higher sustained viral response (SVR) rate to anti-HCV
therapy compared to
interferon (IFN)-based regimens. However, 5% of
hepatitis C patients who undergo DAA
therapy still suffer from a sustained HCV
infection.
MicroRNA (
miRNA) is essentially interfering, endogenous
noncoding RNA that has been investigated as a new
biomarker for the response to DAA in
hepatitis C patients. Here we used a
miRNA array and real-time polymerase chain reaction (PCR) to determine the targetable
miRNA before and 12 weeks after OBV/PTV/r treatment for refractory
hepatitis C. We used replicon cells, in which genotype 1b type HCV is stably transfected in Huh7 cells, to determine whether
miRNA can inhibit HCV replication. Among 2,555
miRNAs, three were significantly up-regulated and eight
miRNAs were down-regulated in serum 12 weeks after OBV/PTV/r treatment. An unsupervised hierarchical clustering analysis, using Pearson's correlation, showed that the
miRNA profiles between before and 12 weeks after OBV/PTV/r treatment were clustered separately. At 12 weeks after OBV/PTV, miR-636 was targeted among the eight down-regulated
miRNAs, and the expression level of circulating miR-636 was significantly diminished. The amount of HCV-
RNA was significantly diminished 48 hours after miR-636 inhibitor transfection in HCV replicon cells. In conclusion, miR-636 might be one of the essential targetable molecules in HCV patients who undergo DAA
therapy and still suffer from a sustained HCV
infection.