Weight-adjusted dosing of ribavirin and importance of hepatitis C virus RNA below 1000 IU/mL by day 7 in short-term peginterferon therapy for chronic genotype 2/3 hepatitis C virus infection
Authors: Martin Lagging, Nina Langeland, Court Pedersen, Martti Färkkilä, Mads Rauning Buhl, Kristine Mørch, Amar P. Dhillon, Åsa Alsiö, Kristoffer Hellstrand, Johan Westin, Peer Christensen, Peter Leutscher, Gunnar Norkrans
Journal: Hepatology (2008)

AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL To the Editor: Dalgard and Mangia address an important issue in the treatment of infections with hepatitis C virus (HCV) genotype 2/3, that is, the putative benefit of adjusting the ribavirin dose for weight rather than, as in our NORDynamIC trial, using a fixed dose. The authors specifically point to a higher relapse rate in patients receiving short-term pegylated interferon (peg-IFN) and ribavirin in the NORDynamIC trial than that observed in their own studies.1-3 These divergent relapse rates may reflect a superiority of weight-adjusted dosing of ribavirin, but may also be explained by differences in demographic characteristics of participating patients. For example, 53% of our patients had bridging fibrosis or cirrhosis, compared to 18% in the study by Mangia et al.,3 and 23% in the pilot study by Dalgard et al.1; in the North-C trial, 17% of patients had an aspartate aminotransferase-to-platelet ratio index score >2, indicating significant fibrosis.2 In support of weight-adjusted ribavirin dosing, as proposed by Dalgard et al., the patients in the NORDynamIC trial who achieved sustained virologic response (SVR) after 24 weeks of therapy had a significantly lower body weight than patients not achieving SVR in the per protocol analysis (mean 75.4 kg versus 84.0 kg, P = 0.016, Mann-Whitney U-test), and a similar albeit nonsignificant trend was observed in patients treated for 12 weeks (78.6 kg versus 83.2 kg, P = 0.11). On the other hand, the larger prospectively randomized trial by Hadziyannis et al. noted no such significant differences between 800 mg and standard weight-based dosing (1000 mg or 1200 mg) of ribavirin for patients infected with genotype 2/3 who were treated for 24 or 48 weeks.4 It is conceivable that weight adjustment of the ribavirin dose may be preferable in short-term therapy for genotype 2/3 infection. However, it is of note that in studies utilizing weight adjustment as well as fixed dosing of the ribavirin, patients achieving rapid virologic response had consistently higher SVR rates and lower relapse rates following standard 24 weeks of therapy compared to patients who had 12-16 weeks of therapy.2, 5, 6 We wish to point out, however, that the NORDynamIC trial identified patients in whom short-term treatment appeared to be acceptably efficacious, that is, the group of patients infected with genotype 2/3 with HCV RNA below 1000 IU/mL already by day 7 (that is, immediately prior to the second dose of peg-IFN). In these patients (which constituted 30% of the intention-to-treat population), 12 weeks of combination therapy using a fixed dose of 800 mg ribavirin daily yielded SVR rates of 92% and 90% in the intention-to-treat analysis in the 12-week and 24-week arms, respectively, and in the per protocol analysis, the SVR rates were 97% and 98% (Fig. 1). Short-term treatment thus appears to be suitable as a response-guided therapy for patients infected with genotype 2/3 with a very rapid virologic response, especially if they are adherent to combination therapy. Figure 1Open in figure viewerPowerPoint Histogram displaying the percent of patients with HCV RNA below 1000 IU/mL by day 7 who achieved (gray bars) or did not achieve (black bars) SVR; 360 patients in the intention-to-treat analysis and 286 patients in the per protocol analysis had plasma HCV RNA samples available by day 7. References 1 Dalgard O, Bjoro K, Hellum KB, Myrvang B, Ritland S, Skaug K, et al. Treatment with pegylated interferon and ribavarin in HCV infection with genotype 2 or 3 for 14 weeks: a pilot study. HEPATOLOGY 2004; 40: 1260– 1265. 2 Dalgard O, Bjoro K, Ring-Larsen H, Bjornsson E, Holberg-Petersen M, Skovlund E, et al. Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response. HEPATOLOGY 2008; 47: 35– 42. 3 Mangia A, Santoro R, Minerva N, Ricci GL, Carretta V, Persico M, et al. Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3. N Engl J Med 2005; 352: 2609– 2617. 4 Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004; 140: 346– 355. 5 Lagging M, Langeland N, Pedersen C, Farkkila M, Buhl MR, Morch K, et al. Randomized comparison of 12 or 24 weeks of peginterferon alpha-2a and ribavirin in chronic hepatitis C virus genotype 2/3 infection. HEPATOLOGY 2008; 47: 1837– 1845. 6 Shiffman ML, Suter F, Bacon BR, Nelson D, Harley H, Sola R, et al. Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3. N Engl J Med 2007; 357: 124– 134. Martin Lagging*, Nina Langeland , Court Pedersen , Martti Färkkilä?, Mads Rauning Buhl?, Kristine Mørch , Amar P. Dhillon**, Åsa Alsiö*, Kristoffer Hellstrand*, Johan Westin*, Peer Christensen , Peter Leutscher?, Gunnar Norkrans*, * Department of Infectious Diseases, Göteborg University, Göteborg, Sweden, Department of Infectious Diseases, Haukeland University Hospital and Institute of Medicine, University of Bergen, Bergen, Norway, Department of Infectious Diseases, University of Southern Denmark, Denmark, ? Department of Gastroenterology, Helsinki University, Helsinki, Finland, ? Department of Infectious Diseases, Aarhus University, Aarhus, Denmark, ** Department of Histopathology, Royal Free Hospital, London, UK. Citing Literature Volume48, Issue2August 2008Pages 695-695 FiguresReferencesRelatedInformation