35 The results for G2 and G3 provided by this meta-analysis are the most useful for future clinical practice, as no phase III trial using new molecules has yet been carried out on this population. Only the question of reducing treatment duration in rapid responders has been thoroughly explored and remains controversial:

The ACCELERATE study contradicts previous trials, but stands as the reference trial because of the number of patients click here studied and the quality of the methodology. It is, nonetheless, interesting to observe that the results of our meta-analysis include this trial, but contradict its findings on some key points. The significant differences obtained in this trial were so small that the clinical significance of its statistically significant differences must be

challenged. This question was particularly relevant in the subpopulation of G2 rapid virologic responders, as already mentioned36: The difference in SVR obtained with a 24-week duration was limited in the ACCELERATE study and was no longer significant in our meta-analysis. However, our most interesting conclusion is that the effect of duration fades when antiviral treatment is more intense. Selleckchem p38 MAPK inhibitor This is shown by the difference obtained when analyzing the subgroup of patients receiving a weight-adjusted ribavirin regimen, instead of a fixed dose of 800 mg/day. When patients received 16 weeks of treatment with weight-adjusted ribavirin, no trend toward better SVR rates in the 24-week arm was seen (Fig. 3A).

A nonsignificant difference was also observed in a post-hoc analysis of the ACCELERATE study focusing on patients <65 kg body weight (i.e., in which the 800-mg/day ribavirin dose was adequate37.) We assume that G2/G3 rapid virologic responders must, therefore, receive a sufficient dose of ribavirin as far as tolerance allows, which is more important than maintaining duration at 24 weeks. Our second study does not answer all questions on optimizing classic bitherapy in hepatitis C. The first question involves taking the viral load into account at week 8. Mangia’s study shows that this could determine the probability of a SVR perhaps more effectively than the response at week 12.21 Other trials did not study this issue, so we could not examine it. The second question concerns the administration of ribavirin. Recent studies suggest that plasma concentration, erythrocyte ribavirin, or drop in hemoglobin under ribavirine38 correlated with ribavirin concentration, are predictive factors for SVR. No trial in our meta-analysis involved pharmacological follow-up of ribavirin or a sequential measurement of hemoglobin, or even an identical procedure for a decrease in ribavirin or for erythropoietin administration in the event of adverse effects.