Ribavirin steady-state plasma level is a predictor of sustained virological response in hepatitis C-infected patients treated with direct-acting antivirals

van Tilborg, M., Lieveld, F. I., Smolders, E. J., van Erpecum, K. J., de Kanter, C. T. M. M., Maan, R., van der Valk, M., Arends, J. E., Dofferhoff, A. S. M., Blokzijl, H., Bijmolen, M., Drenth, J. P. H., de Knegt, R. J., Burger, D. M. & HepNed Study Grp, Nov-2017, In : Alimentary Pharmacology & Therapeutics. 46, 9, p. 864-872 9 p.

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  • Ribavirin steady-state plasma level is a predictor of sustainedvirological response in hepatitis C–infected patients treatedwith direct-acting antivirals

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  • M. van Tilborg
  • F. I. Lieveld
  • E. J. Smolders
  • K. J. van Erpecum
  • C. T. M. M. de Kanter
  • R. Maan
  • M. van der Valk
  • J. E. Arends
  • A. S. M. Dofferhoff
  • H. Blokzijl
  • M. Bijmolen
  • J. P. H. Drenth
  • R. J. de Knegt
  • D. M. Burger
  • HepNed Study Grp

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 (ie treatment experienced, HCV genotype 3, cirrhosis). The majority was treated with a sofosbuvir-based regimen and 163 (89%) patients achieved SVR. Median RBV dose was 12.9 (interquartile range 11.2-14.7) mg/kg/d, and median RBV steady-state plasma level was 2.66 (1.95-3.60) mg/L. In multivariable analyses, higher RBV steady-state plasma level (adjusted odds ratio 1.79 [95% CI 1.09-2.93]) 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 (Haemoglobin <10 g/dL).

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.

Original languageEnglish
Pages (from-to)864-872
Number of pages9
JournalAlimentary Pharmacology & Therapeutics
Issue number9
Publication statusPublished - Nov-2017



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