The purpose of this pilot study was to assess the efficacy and safety of a 6-month course of 6 million units (MU) of leukocyte interferon alfa (IFN-α) 3 times a week (TIW) in naive patients with chronic hepatitis C virus (HCV) infection. Nine patients were treated with leukocyte IFN-α at a dose of 6 MU TIW; a control group of 30 patients received the standard regimen of leukocyte IFN-α 3 MU TIW. All patients were treated for 6 months and followed up for an additional 6 months. Biochemical (alanine aminotransferase [ALT] values) and virologic (HCV-RNA) responses to treatment were assessed. At the end of the treatment period, 6 (67%) of 9 patients treated with IFN-α 6 MU showed normal ALT levels compared with 14 (47%) of 30 patients treated with 3 MU. The complete (biochemical and virologie) response was slightly greater in patients treated with 6 MU (3/9, 33%) than in those treated with 3 MU (7/30, 23%), both at the end of treatment or after 6 months of follow-up. Both of the IFN regimens were well tolerated. Results of this pilot study suggest that treatment with 6 MU of leukocyte IFN-α TIW for 6 months is associated with a slightly better biochemical and virologic response than is treatment with the standard regimen of 3 MU TIW for 6 months. These results, however, should be confirmed in a larger trial with a high power.

Standard treatment for chronic hepatitis C currently consists of 3–6 million units (MU) of interferon‐α (IFN‐α) given thrice weekly (t.i.w.) for 12 months, obtaining rates of sustained response (SR) that usually do not exceed 15–25%. Some recent reports have suggested that daily administration of IFN‐α may be more efficacious. More than 7 years ago, when standard therapy for hepatitis C was usually given for 6 months, we conducted a randomized clinical trial comparing daily vs t.i.w. treatment. In this study, 149 patients with chronic hepatitis C were randomized to received 3 MU of IFN‐α either t.i.w. for 6 months or daily for 3 months followed by t.i.w. for 3 months. All patients were treated with human leucocyte IFN‐α and were followed‐up for up to 72 months after inclusion. Overall, patients treated daily or t.i.w. had similar rates of virological response after 3 months of induction [24/49 (50%) vs 40/100 (40%)], at the end of therapy [15/49 (31%) vs 36/100 (36%)] and at the end of follow‐up [6/49 (12%) vs 9/100 (9%)]. However, when patients infected with HCV types other than HCV‐1 were studied, there was a trend favouring the daily schedule that was associated with a higher [5/20 (25%) vs 5/48 (10%)] rate of long‐term SR. All patients with a virological response – hepatitis C virus (HCV) RNA negative in serum as determined using the polymerase chain reaction – at 6 months after therapy remained in biochemical and virological remission at long‐term follow‐up, while seven of eight subjects who had normal alanine aminotransferase (ALT) levels but were serum positive for HCV RNA at 6 months, relapsed later, indicating that serum HCV RNA is better than ALT at predicting long‐term cure after IFN‐α therapy in chronic hepatitis C.

Alpha-interferon (IFN-α) is an effective treatment for chronic hepatitis C, but only 20% to 30% of patients are apparently cured with the currently recommended schedule of 3 MU given three times a week for 6 months. To evaluate the efficacy of more aggressive treatment regimens, we have conducted a randomized trial in 174 patients with chronic hepatitis C using three different schedules: (1) 12-month treatment starting with 6 MU/three times a week and decreasing the dose on the basis of serum alanine transaminase (ALT) activities (group A: 59 cases); (2) fixed dose of 3 MU three times a week for 12 months (Group B: 61 cases), (3) fixed dose of 6 MU three times a week for 6 months (Group C: 54 cases). Patients were evaluated during therapy for biochemical and virological response and followed for at least 12 months after therapy to assess long-term efficacy and liver histological outcome. The genotype of infecting HCV was also analyzed in all patients, and predictors of response were determined by multivariate analysis. Serum ALT became normal during therapy in 76% of patients (95% confidence interval [CI]: 63 to 86), 65% (CI: 52 to 77), and 74% (CI: 60 to 85) in groups A, B, and C, respectively (P = NS). The corresponding figures for sustained response 12 months after therapy were 49% (CI: 36 to 62), 31% (CI: 20 to 44), and 28% (CI: 16 to 42) (A vs. B, P = .06; A vs. C, P = 0.03). Eighty-six percent of patients with sustained response cleared HCV-RNA from serum and 72% improved histologically. Patients infected with HCV genotypes 2a and 3 had higher sustained response rates than those with 1b, independent of treatment schedule. In patients infected with genotype 1b, the rate of sustained response was related to dose and duration of therapy being 28% with schedule A, 16% with schedule B, and 9% with schedule C. Multivariate analysis indicated that younger age (P = .016), shorter disease duration (P = .003), and infection with HCV genotypes 2a (P = .0017) and 3 (P = .0083) were independent predictors of sustained response. These results indicate that sustained response to IFN-α in chronic hepatitis C is affected by dose and duration of therapy, particularly in patients infected with HCV genotype 1b.

Division of Infectious Disease and *Department Pathology, Civil Hospitals of Venice, Venice, Italy.