Predicting response to initial therapy with interferon plus ribavirin in chronic hepatitis C using serum HCV RNA results during therapy

In patients with chronic hepatitis C, 48 weeks of therapy with interferon ( IFN) plus ribavirin results in a sustained virologic response of 40%. Preli minary analysis suggests that measuring HCV RNA at week 24, rather than wee k 12, might provide the best prediction of treatment response. To assess th e clinical utility of serum HCV RNA determinations at different times durin g therapy as a predictor of a sustained virologic response we evaluated 912 treatment-naive patients. Patients were randomized to receive IFN-alpha 2b , 3 million units (MU) three times weekly (tiw), for 24 or 48 weeks with ei ther ribavirin or placebo, and then followed for 24 weeks. Serum HCV RNA wa s measured at weeks 4 and 12 in patients treated for 24 weeks; at 4, 12, an d 24 weeks during therapy in those treated for 48 weeks, and week 24 post-t herapy in all patients. Sustained response was defined as loss of serum HCV RNA at week 24 follow-up. Other patients were considered virologic nonresp onders. For patients receiving 48 weeks of combination therapy, detectable serum HCV RNA at week 24 predicted nonresponse (positive predictive value) in 99% of patients compared to 89% at week 12. In patients treated for 24 w eeks, testing at week 12 was more predictive of nonresponse than testing at week 4 in the combination-therapy croup but not in the monotherapy group. Hence, for combination therapy, testing for serum HCV RNA as a predictor of nonresponse is most accurate at week 24 of therapy; a positive test correc tly identified 99% of nonresponders.