Ribavirin plasma concentration is a predictor of sustained virological response in patients treated for chronic hepatitis C virus genotype 2/3 infection

Journal of Viral Hepatitis

Early View (Articles online in advance of print)
Published Online: 1 Apr 2010
© 2010 Blackwell Publishing Ltd

C. Pedersen 1 , Å. Alsiö 2 , M. Lagging 2 , N. Langeland 3 , M. Färkkilä 4 , M. Rauning Buhl 5 , K. Mørch 3 , J. Westin 2 , P. Sangfelt 6 , G. Norkrans 2 and P. Brehm Christensen 1 for the NORDynamicIC Study Group

1 Department of Infectious Diseases, University of Southern Denmark, Odense C, Denmark and Department of Infectious Diseases, Herlev Hospital, Copenhagen, Denmark ; 2 Department of Infectious Diseases, Göteborg University, Göteborg, Sweden ; 3 Department of Infectious Diseases, Haukeland University Hospital and Institute of Medicine, University of Bergen, Bergen, Norway ; 4 Department of Gastroenterology, Helsinki University, Helsinki, Finland ; 5 Department of Infectious Diseases, Skejby Hospital, Aarhus University, Aarhus, Denmark ; and 6 Department of Infectious Diseases, Uppsala University Hospital, Uppsala, Sweden

Correspondence to Court Pedersen, Department of Infectious Diseases Q, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark. E-mail: court.pedersen@ouh.regionsyddanmark.dk

KEYWORDS
drug concentration • hepatitis C • ribavirin • treatment

ABSTRACT
Summary. In hepatitis C virus (HCV) genotype 1 infection, the likelihood of obtaining sustained virological response (SVR) is associated with higher ribavirin exposure. Such an association has not been demonstrated for HCV genotype 2/3 infection, where a fixed 800 mg daily dosing of ribavirin is generally recommended. The primary aim of this study was to investigate the correlation between ribavirin concentration at day 29 and therapeutic response in patients with HCV genotype 2/3 infection. A total of 382 patients were randomized to 12 or 24 weeks of treatment with pegylated interferon-alfa 2a 180 μg weekly and 800 mg ribavirin daily. Trough plasma concentration of ribavirin was measured at day 29 and week 12 and the primary outcome was SVR (HCV-RNA undetectable 24 weeks after treatment). Of the 382 patients, 355 had a ribavirin concentration available at day 29. SVR was 84% among patients with a ribavirin concentration ≥2 mg/L at day 29 compared to 66% in those with concentrations <2 mg/L (P = 0.002). The corresponding figures in the 12-week treatment group were 74% and 57% (P = 0.12), and in the 24-week treatment group 91% and 75% (P = 0.02), respectively. In a multivariate analysis, ribavirin concentration at day 29 was an independent predictor of SVR (P = 0.002). In conclusion, a higher plasma ribavirin concentration is associated with an increased likelihood of achieving SVR in HCV genotype 2/3 infection. Individualization of ribavirin dosing may be helpful in improving outcome, especially in the presence of unfavourable baseline characteristics. This, however, requires evaluation in a prospective trial.
Received October 2009; accepted for publication January 2010

DIGITAL OBJECT IDENTIFIER (DOI)
10.1111/j.1365-2893.2010.01303.x About DOI
 
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