Background: In the era of highly effective direct-acting antivirals (DAAs) for treatment of patients with chronic hepatitis C virus (HCV) infection, ribavirin (RBV) is still considered beneficial in certain patients.
Aim: To assess the association between RBV steady-state plasma levels and sustained virological response (SVR).
Methods: Consecutive HCV-infected patients treated with DAAs plus RBV from four Dutch academic medical centres were enrolled. RBV steady-state plasma levels were prospectively measured at treatment week 8 using validated assays. Logistic regression analyses were performed to assess the influence of RBV steady-state plasma level on SVR, and RBV therapeutic range was explored using area under the ROC curve analyses.
Results: A total of 183 patients were included, of whom 85% had one or more difficult-to-cure characteristics. The majority was treated with a sofosbuvir-based regimen and 163 patients achieved SVR. Median RBV dose was 12.9 mg/kg/d, and median RBV steady-state plasma level was 2.66 mg/L. In multivariable analyses, higher RBV steady-state plasma level was an independent predictor of SVR. With regard to the optimal RBV therapeutic range, 2.28 mg/L was the optimal lower cut-off for achieving SVR and 3.61 mg/L was the upper cut-off for preventing significant anaemia.
Conclusion: In this cohort of mainly difficult-to-cure patients treated with DAAs plus RBV, higher RBV steady-state plasma level was an independent predictor of SVR.

Additional Metadata
Persistent URL dx.doi.org/10.1111/apt.14288, hdl.handle.net/1765/101861
Journal Alimentary Pharmacology and Therapeutics
Citation
van Tilborg, M, Lieveld, F.I, Smolders, E.J. (E. J.), van Erpecum, K.J, de Kanter, C.T.M.M, Maan, R, … Burger, D.M. (2017). Ribavirin steady-state plasma level is a predictor of sustained virological response in hepatitis C-infected patients treated with direct-acting antivirals. Alimentary Pharmacology and Therapeutics. doi:10.1111/apt.14288