Clinical treatment for HCV infection reverses CYP2C19 inhibition.

Aim Infection by the hepatitis C virus (HCV) generates inflammatory response selectively modulating CYP activities. This study assessed the effect of chronic hepatitis C on CYP2C19 activity in patients with HCV. Methods 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 2 mg single oral dose of omeprazole (OME) as probe a drug in both phases. Metabolic ratios (MR) (plasma samples collected at 4 h after OME administration) were calculated dividing plasma concentrations of 5-hydroxyomeprazole by OME. Results The MR's for group 1 were 0.45 (0.34-0.60, 90% CI) and 0.69 (0.50-0.96) for phases 1 and 2, respectively; while the MR's for group 2 were 0.25 (0.21-0.31) and 0.41 (0.30-0.56) for phases 1 and 2, respectively. MR's were different (p 0.05). Conclusion Both groups presented different MR's before and after treatment with DAAs, evidencing that CYP2C19 inhibition during inflammation was at least partially reversed after DAAs treatment. Groups 1 and 2 were also found different in phase 1 but not phase 2, showing that CYP2C19 metabolic activity does not differ between groups after DAAs treatment.