Efficacy of Peginterferon Alpha-2a vs. 2b for the Treatment of Chronic HCV: Interpretation of Results and Future Prospects

I their meta-analysis of the efficacy of peginterferon alfa-2a (PEG-IFN-α2a) or alfa2b (PEG-IFN-α2b) and ribavirin for the treatment of hepatitis C virus (HCV), Alavian et al. (1), analyzing pooled data from 7 studies, conclude that PEG-IFNα2a (with similar safety) is more effective than PEGIFN-α2b. While PEG-IFN alfa-2b with ribavirin is generally considered as the treatment of choice for chronic HCV infection (2), the findings of this study sound at first like good news, especially since PEG-IFN alfa-2a is more cost-effective than PEGIFN alfa-2b (3); but we suggest that the findings of this study should be open to a more conservative interpretation. Because of the nature of meta-analysis, we cannot expect in the current article to consider all the major factors that may interfere or otherwise affect the efficacy or safety of PEG-IFNs. In Alavian’s study, it was well demonstrated that PEG-IFN alfa-2a provides a higher virologic response than that of alfa2b. However, several factors that can interfere, such as insulin resistance, racial factors (Asian patients respond better to PEG-IFN, but there is a greater incidence of adverse events among them), gender effect (females respond better to therapy), in addition to some genetic factors, were not included in this analysis; moreover, the study would have been more informative if genotype 1 of HCV were analyzed separately, since this genotype represents the most resistant type of HCV infection. A higher prevalence of neutropenia among patients treating with PEG-IFN alfa-2a was another interesting finding of the previously mentioned meta-analysis. Here we raise a question about the logic behind the disparities found: Can these observations be explained by a dose-response effect? McHutchison et al. (4) in their study found that a higher dosage of PEG-IFN alfa-2b is associated with a higher percentage in sustained virologic response (SVR), while a lower dosage was associated with a substantial decrease in neutropenia and anemia. According to these findings, we might be able to simply conclude that administration of a higher dosage of PEG-IFN alfa-2b may result in a higher SVR rate as well as neutropenia, comparable to that of PEG-IFN alfa-2a.