Chronic Hepatitis C Virus Patients With Breakthroughs During Interferon Treatment Can Successfully Be Retreated With Consensus Interferon
Heathcote EJL, James S, Mullen KD, et al.
Hepatology 30(2):562-566, August 1999

Individuals with chronic hepatitis C virus (HCV) infection who have not demonstrated a sustained HCV-RNA response or serum alanine transaminase (ALT) response to a 6-month course of interferon (IFN) may respond to higher-dose retreatment with consensus interferon (CIFN). Furthermore, a proportion of nonresponders to initial therapy with IFN show a transient response (defined as undetectable HCV RNA or normalization of ALT) during treatment, but later have a "breakthrough" while still on treatment.

Do nonresponders who have breakthroughs respond differently to CIFN retreatment from nonresponders without breakthroughs?

Heathcote and colleagues conducted this large, multicenter trial which involved 704 patients randomized to treatment with either CIFN (3mcg or 9mcg) or IFN-alfa 2b (3 MU), 3 times weekly for 6 months; there was a 6-month follow-up observation period. Final analyses included 467 patients from 2 of  the treatment groups (the 3-mcg CIFN treatment group was excluded because this dosing schedule was less effective than the 9-mcg regimen). Patients who did not demonstrate a sustained response to the initial 9-mcg CIFN or 3-MU IFN-alfa 2b were eligible for retreatment with 15mcg of CIFN 3 times per week for either 6 or 12 months.

Results showed that in general, approximately one third of patients considered nonresponders have breakthroughs during IFN treatment when serum HCV RNA and ALT levels are tested frequently. When nonresponders were retreated with CIFN for 12 months, 27% of those with previous viral breakthroughs had a sustained viral response compared with 8% in prior nonresponders without breakthroughs. Additionally, sustained ALT responses occurred in 39% of patients with prior breakthroughs compared with 10% of patients without previous breakthroughs.

As these authors conclude, these findings suggest that prior nonresponders with breakthroughs have a greater chance of responding to retreatment than do nonresponders without breakthroughs. Therefore, while these data indicate that patients who experience HCV-RNA or ALT breakthroughs can be effectively retreated with CIFN, most breakthrough patients are missed unless HCV-RNA testing is conducted at frequent intervals during initial IFN therapy.  Don't let what you can't do stop you from doing what you can