Background : Hepatitis C viral kinetic studies have demonstrated the increased anti-viral effect of higher than standard dosages of interferon and of daily treatment schedules.
Aim : To compare, in a prospective, randomized, controlled trial, the efficacy and safety of high-dose interferon-α therapy vs. standard-dosage interferon-α therapy, in a triple therapy combination with ribavirin and amantadine.
Methods : Previously untreated patients with chronic hepatitis C were randomized to the standard interferon-α group (n = 15), receiving thrice weekly 6 MU interferon-α for 12 weeks, followed by 3 MU interferon-α for 36 weeks, or the high-dose interferon-α group (n = 15), receiving daily 9 MU interferon-α for 4 weeks, followed by 6 MU (weeks 5–8), 3 MU (weeks 9–12) and 1.5 MU (weeks 13–48) interferon-α. All patients were given ribavirin (1000–1200 mg) and amantadine (200 mg) daily for 48 weeks.
Results : At the end of treatment and after the 24-week follow-up period, serum hepatitis C virus RNA was undetectable in eight (53%) and six (40%) patients treated with standard-dosage interferon-α, respectively, compared with 11 (73%) and 10 (67%) treated with high-dose interferon-α, respectively (not significant). The safety profile of both treatment regimens was similar. Severe adverse events leading to withdrawal from the study occurred in one patient (7%) in each group, and in both groups one patient (7%) was lost during therapy for unknown reasons.
Conclusions : The findings suggest that, although the difference between the response rates of standard and high-dose interferon-α regimens (within a triple anti-viral therapy combination) did not reach statistical significance, there was a clear trend towards a higher response with high-dose interferon-α therapy and an equal safety profile.