Optimal dosage of ribavirin

Abstract

We read with interest the article by Diago et al.,1 who attempted to identify factors predictive of sustained virological response (SVR) in patients with hepatitis C virus genotype 2 or 3 who were treated for only 16 weeks with peginterferon alfa-2a and flat doses of ribavirin. After a 5-year-long debate about the value of abbreviated antiviral therapy for naive patients infected with hepatitis C virus genotype 2 or 3, a general agreement seems to have been reached. An abbreviated regimen may be an option in patients with rapid virological response (RVR), lower body weight, and an absence of advanced fibrosis. This proposal, which was originally based on our data,2 has found successive support in the trial by Dalgard et al.3 and recently in repetitive analyses of results generated by the ACCELERATE study.4 What remains to be further stressed is the optimal dosage of ribavirin to be administered when short-term therapy is being contemplated. In two studies, a flat dose of 800 mg daily was administered, and the highest difference in SVR rates between patients treated for a short duration and patients treated for the standard duration was reported.3, 5 On the contrary, when higher doses were given (1000-1200 mg daily), this difference was not significant or was barely significant.1, 2 In Diago et al.'s reanalysis,1 only patients with RVR were considered, and the authors found body weight to be inversely related to either the SVR or the relapse rate. Indeed, among patients with low body weights (<65 kg) who were assigned to 16 or 24 weeks of treatment, SVR rates were 89% and 93%, respectively, and the respective relapse rates were 7% and 3%. The resulting differences were not significant, and this implies that when the ribavirin dosage (mg/kg of body weight) is given at a higher dosage than that conventionally suggested, short-term therapy is as effective as therapy of the standard duration. As a matter of fact, in the subset of patients with high body weights (>65 kg), the administration of 800 mg of ribavirin would not be enough to protect them from lower SVR rates and higher relapse rates. We have recently stressed the relevance of administering adequate doses of ribavirin (>15.2 mg/kg of body weight) when a short treatment duration is being considered for genotype 2 and 3–infected patients without advanced fibrosis/cirrhosis who achieve RVR,6 and the data presented by Diago et al. reinforce our original findings. Consequently, determining the ribavirin dosage by body weight is the first step in further consideration of predictors of SVR. This point has not been addressed in the reanalysis of the ACCELERATE study presented by Diago et al.,1 who have evaluated only the impact of ribavirin exposure on SVR rates. Alessandra Mangia M.D.*, Angelo Andriulli M.D. , * Liver Unit, Ospedale Casa Sollievo della Sofferenza San Giovanni Rotondo, Italy, Gastroenterology, Ospedale Casa Sollievo della Sofferenza San Giovanni Rotondo, Italy.