High-dose interferon-α2b for re-treatment of nonresponders or relapsing patients with chronic hepatitis C

Abstract

Relatively few patients with chronic hepatitis C treated with standard doses of interferon-alpha 2b (3 million units per week for 24 weeks) have a sustained response. Our aim was to evaluate whether higher doses of interferon would improve this rate of response. Twenty-four patients with chronic hepatitis C who had failed to respond to (N = 21) or had relapsed after (N = 3) an initial course of standard interferon therapy were randomized to 15 million units (N = 13) or 22.5-30 million units per week (N = 11) for 24 weeks. Five of 13 subjects given 15 million units per week and 3/11 of subjects given 22.5-30 million units per week had complete normalization of serum alanine aminotransferase levels during therapy. Five patients (24% who had not responded to standard interferon had a complete response to high-dose interferon during therapy. Only one patient had a sustained response, with normal serum alanine aminotransferase 24 weeks after stopping interferon. Six patients were withdrawn before completing treatment, five in the 22.5-30 million unit per week group. We conclude that higher doses of interferon ameliorate the severity of hepatitis in patients who failed to respond to or relapsed after standard interferon therapy, but are unlikely to produce a sustained response. High-dose therapy is associated with an increase in side effects.

Pilot Study of Interferon-α with and without Amantadine for the Treatment of Hepatitis C in HIV Co-infected Individuals on Antiretroviral Therapy

“…In contrast to current recommendations, we used a higher dose and daily application (during the 1st month) of interferon-␣ because recent data suggested improved response rates with this dosing schedule [18]. This higher initial dose may explain the toxicity, as also observed by others [19], but did not seem to have an improved sustained therapeutic effect among our patient group.…”

Interferon Alfa-2b Alone or in Combination with Ribavirin for the Treatment of Relapse of Chronic Hepatitis C

“…The results of previous studies of the importance of changes in HCV RNA levels with respect to the response to treatment with interferon after relapse are conflicting, 37,41,42 possibly because of differences in the method of serum collection, 26 the HCV RNA assay, 43 or the viral response to the first course of treatment. Patients in whom serum alanine aminotransferase concentrations return to normal and serum HCV RNA levels become undetectable during the first course of interferon are more likely to have a response to treatment after relapse than those in whom serum alanine aminotransferase values return to normal but viremia persists.…”

Chronic hepatitis C: Interferon retreatment of relapsers. A meta-analysis of individual patient data

“…These included age, higher ALT levels, lower ␥-glutamyltransferase levels, negative HCV RNA at the end of the first cycle, low levels of HCV RNA before retreatment, and increased IFN dose in the second course. 2,4,[6][7][8][9]14 Finally, Chow et al 3 failed to identify any predictive item significantly associated with an SR. The drawing of firm conclusions based on the results of these studies is hampered by the small sample size and by the imbalance between the high number of variables included in multivariate models and the small number of events observed, potentially leading to false-negative or false-positive results.…”