I read with interest the article by Bacon et al.1 dealing with the retreatment of chronic hepatitis C with daily interferon alfacon-1 (CIFN)/ribavirin (RBV) for patients who were nonresponders to pegylated interferon (PEG-IFN)/RBV. As expected, the treatment of these patients who were nonresponders to PEG-IFN/RBV has been very difficult. Several studies have evaluated the efficacy of retreatment with PEG-IFN/RBV and some successes have been achieved. Overall response rates ranging from 18%–41% have been reported.2–4 Generally, previous nonresponders (defined as detectable hepatitis C virus [HCV] RNA at the end of treatment) had a lower sustained virological response (SVR), whereas previous relapsers (defined as undetectable HCV RNA at the end of therapy) had a higher SVR.4
Because this trial by Bacon et al. enrolled patients who had a < 2 log10 decrease in HCV RNA between weeks 12 and 24 or detectable HCV RNA at weeks 24 or 48, the rates of previous nonresponders and relapsers were not disclosed. This study showed that SVR rates were 6.9% in the 9-μg group and 10.7% in the 15-μg group. Only a subgroup of patients (with fibrosis scores of F0–F3) who received 15 μg could achieve SVR in 31.6% of individuals if a > 2 log10 decrease in HCV RNA was attained with previous PEG-IFN/RBV therapy. The proportion of patients who could not tolerate adverse events of CIFN/RBV and who required discontinuation was up to 17.7%. The authors concluded that retreatment of nonresponders to PEG-IFN/RBV with CIFN/RBV is safe and efficacious. Undeniably, the SVR would be 0% in patients who experienced PEG-IFN/RBV treatment failure, under “watchful waiting”. However, if the SVR ranging from 6%–10% was interpreted as efficacious, this may be misleading for readers. Overall, the alternative strategies for improving SVR in PEG-IFN/RBV nonresponders have not met with success just like that stated by the authors. Based on the current data, retreatment of chronic hepatitis C with daily CIFN/RBV for patients who were nonresponders to PEG-IFN/RBV should be interpreted as ineffective except for a subgroup of patients.