Clinical treatment for hepatitis C reverses CYP2C19 inhibition.

Abstract

Infection by the hepatitis C virus (HCV) generates inflammatory response selectively modulating cytochrome P450 protein (CYP) activities. This study assessed the effect of chronic hepatitis C on CYP2C19 activity in patients with HCV. Patients with HCV infection (n = 23) at different fibrosis stages were allocated into groups 1 (F0/F1 and F2, mild to moderate fibrosis) and 2 (F3 and F4, advanced fibrosis stages). Phase 1 was conducted before the treatment with direct-acting antivirals (DAAs) and phase 2 after the sustained virological response. Participants were administered 2mg of a single oral dose of omeprazole (OME) as probe drug in both phases. Metabolic ratios (MRs) (plasma samples collected at 4h after OME administration) were calculated by dividing plasma concentrations of 5-hydroxyomeprazole by OME. The MRs for group 1 were 0.45 (0.34-0.60, 90% confidence interval) and 0.69 (0.50-0.96) for phases 1 and 2, respectively, while the MRs for group 2 were 0.25 (0.21-0.31) and 0.41 (0.30-0.56) for phases 1 and 2, respectively. MRs were different (P < .05) between phases 1 and 2 for both groups, as well as between groups 1 and 2 in phase 1, but not in phase 2 (P > .05). Both groups presented different MRs before and after treatment with DAAs, evidencing that CYP2C19 inhibition during inflammation was at least partially reversed after DAA treatment. Groups 1 and 2 were also found to be different in phase 1 but not phase 2, showing that CYP2C19 metabolic activity does not differ between groups after DAA treatment.