Treatment of chronic hepatitis C virus infection with recombinant consensus interferon.

To assess the safety and efficacy of consensus interferon (IFN-Con-1), 55 patients with chronic hepatitis C infection were treated with either 3, 6, 9, 12, or 15 microg IFN-Con-1 s.c. three times a week for 24 weeks, followed by 24 weeks of observation. There was a dose-response relationship with respect to the number of patients with normalized ALT concentrations or undetectable HCV RNA. At the end of the 24-week treatment period, the serum ALT had normalized in 18% of patients given the 3 microg dose and 42% of patients given the 12 microg or 15 microg doses of IFN-Con-1. At the end of the posttreatment observation period, the serum ALT was still normal in 10% of patients given the 3 microg, 6 microg, or 9 microg doses and in 50% of patients given the 15 microg dose. Also, at the end of the 24-week treatment period, 27% of patients given the 3 microg dose and 75% given the 15 microg dose had undetectable serum HCV RNA. At the end of the posttreatment observation period, the proportion of patients with undetectable HCV RNA ranged from 9% of those given the 3 microg dose to 50% of those given the 15 microg dose. Our study indicates that treatment with IFN-Con-1 appears to be safe and effective. In addition, use of 15 microg of IFN-Con-1 resulted in significantly more patients with sustained ALT normalization and absence of HCV RNA 6 months after cessation of therapy compared with treatment with lower doses of IFN-Con-1. Additional trials are underway to confirm these findings.

Long-term retreatment in chronic hepatitis C patients who were non-responders to an initial course of interferon-alpha 2b.

Nineteen patients with chronic hepatitis C who were virological non-responders (seven responder/relapse and 12 no response) to an initial 24-week course of interferon-alpha 2b (IFN-alpha 2b) at a dose of 3 million units (MU) thrice weekly were retreated for an additional 48 weeks at the same dosing schedule and followed-up for another 24 weeks post-therapy. At the end of follow-up (week 72), six (32%) of the 19 patients were hepatitis C virus (HCV) RNA negative and were virological complete responders to retreatment. The viral genotypes in these six patients included two each with 1b and 3a, one with 2b, and another with 2a/2b; five of the six virological responder patients had cirrhosis. Significant predictors for successful retreatment included lower baseline HCV RNA concentrations prior to the first course of therapy, 2 log10 reductions in serum HCV RNA during the initial treatment and classification into the virological 'responder/relapse' category after the first course of IFN (P < 0.01 for all observations). When the above factors were used to construct a predictive model to determine response to retreatment, it was found that the absence of a 2 log10 drop in HCV RNA concentrations during the first course of IFN therapy was the most reliable indicator of non-response to retreatment (likelihood ratio = 10, P = 0.0014). In addition, the presence of HCV RNA at week 12 of retreatment was 100% predictive of virological non-response to the 48-week course of therapy. Our findings indicate that an additional 48-week course of IFN-alpha 2b therapy at 3 MU thrice weekly will achieve a virological complete response in 60% of patients who had a 2 log10 drop in HCV RNA during their first course of treatment, and measurement of week-12 HCV RNA during retreatment to identify non-responders is beneficial to patients as well as being cost-effective. Thus, a second course of IFN remains a viable option in a subgroup of non-responder patients, regardless of genotype or the presence of compensated cirrhosis.