Predicting treatment outcome following 24 weeks peginterferon α-2a/ribavirin therapy in patients infected with HCV genotype 1: Utility of HCV-RNA at day 0, day 22, day 29, and week 6
Authors: Esther Lukasiewicz, Kristoffer Hellstrand, Johan Westin, Carlo Ferrari, Avidan U. Neumann, Jean-michel Pawlotsky, Solko W. Schalm, Stefan Zeuzem, Bart J. Veldt, Bettina E. Hansen, Elke Verhey-hart, Martin Lagging
Journal: Hepatology (2006)

The post-hoc analysis recently reported by Jensen et al.1 evaluated factors predictive of a favorable outcome of short-term (24-week) treatment with peginterferon and ribavirin for chronic HCV infection. The authors convincingly demonstrate that patients infected with HCV genotype 1 who have undetectable HCV-RNA at week 4 (rapid viral response, RVR) have a high probability of achieving sustained viral response (SVR) following 24 weeks of combination therapy, and that RVR is associated with a higher odds ratio (23.7 versus 2.7) for predicting SVR than is low baseline viral load (<200,000 versus >600,000 IU/ml). In a European HCV multicenter treatment study,2 we treated 178 patients infected with HCV genotype 1 with peginterferon α-2a and ribavirin. Ninety-one of 178 were classified as having a rapid viral decline, i.e., had ≥2 log10 drop of HCV-RNA and a second-phase decline ≥0.09 log10/day during the first 4 weeks of treatment. Twenty-three of these patients received combination therapy for 24 weeks; 15 of these patients (65%) achieved SVR as compared to 39 of 47 (83%) matched controls treated with combination therapy for 48 weeks. Serial analysis of HCV-RNA (Cobas Amplicor HCV version 2.0; detection limit of ≤50 IU/ml) revealed that 5 of 15 patients achieving SVR had undetectable viremia on day 22 (i.e., the day after the fourth dose of peginterferon α-2a). Nine of 14 SVR patients were HCV-RNA negative on day 29 (i.e., the day after the fifth dose of peginterferon α-2a), and a total of 11 patients were negative on week 6; 2 of these patients, however, relapsed following termination of therapy. Interestingly, all 23 matched control patients treated for 48 weeks who had undetectable HCV-RNA on day 29 also achieved SVR. In contrast only 5 of 13 patients (38%) with detectable HCV-RNA at day 29 achieved SVR when treated for 24 weeks of combination therapy as compared to 16 of 23 (70%) of matched controls treated for 48 weeks. Though this difference was not significant (P = 0.09, Fisher's exact test), it suggests that 48 weeks of treatment may be preferential in this group in accordance with the findings by Jensen et al. In agreement with the findings by Jensen et al., we observed that patients with baseline HCV-RNA below the previously reported threshold of 600,000 IU/ml3 were statistically more likely to have undetectable HCV-RNA at day 29 (63% versus 32%, P = 0.01) as well as had a trend toward greater likelihood of achieving SVR (89% versus 50%, P = 0.06). Indeed, 8 of 9 patients with a baseline viral load below 600,000 IU/ml achieved SVR. However, in our study, having a low baseline viral load appeared less clinically useful than undetectable HCV-RNA early during the course of therapy, and when adding these 2 predictors of SVR, fewer patients achieving SVR were identified as compared to undetectable HCV-RNA day 29 alone as demonstrated in Table 1. It is also worth noting in our study that among the 15 patients achieving SVR, only 8 had a baseline viral load below 600,000 IU/ml. Interestingly, in our study, baseline viral load was not predictive of SVR in the matched control patients treated for 48 weeks. In conclusion, these findings support the results presented by Jensen et al. that 24 weeks of combination therapy is feasible in HCV genotype 1 infected patients provided that viremia is cleared early during therapy, and that early HCV-RNA clearance is significantly associated with low baseline viral load. Esther Lukasiewicz* , Kristoffer Hellstrand , Johan Westin , Carlo Ferrari , Avidan U. Neumann* , Jean-michel Pawlotsky? , Solko W. Schalm? , Stefan Zeuzem** , Bart J. Veldt** , Bettina E. Hansen** , Elke Verhey-hart** , Martin Lagging , * Bar-Ilan University, Ramat-Gan, Israel, Department of Infectious Diseases, University of Göteborg, Sweden, Azienda Ospedaliera di Parma, Parma, Italy, ? Hôpital Henri Mondor - Université Paris XII, Creteil, France, ? University Hospital Rotterdam Dijkzigt, Rotterdam, Netherlands, ** Saarland University Hospital, Homburg/Saar, Germany, Department of Virology, Erasmus MC, Rotterdam, Netherlands.