Two years versus six months of interferon therapy for chronic hepatitis C.

Short-term (end-of-treatment) responses (ETR) to interferon (IFN) therapy for chronic hepatitis C are encouraging; however, the relapse rate is high, and long-term response is obtained in only 12-25% of patients. The Australian Hepatitis C Study Group conducted a trial of 230 patients that compared the standard 3 MU three times a week six-month course of IFN-alpha2b with 5 MU three times a week for six months (5 MU group) or 3 MU three times a week for two years (two-year group). ETR (normalization of serum aminotransferase level until the end of treatment) rates based on an intent-to-treat analysis were 64% for the 5 MU group and 58% for the combined 3 MU groups. After six months of treatment, the overall relapse rate was 71%, and the long-term response (LTR; continued normal aminotransferase until six month follow up) rate did not differ significantly between the 3 MU (17% of all treated, 27% ETR) and 5 MU groups (20% of all treated, 31% ETR). In contrast, among the 46 patients who exhibited an ETR in the two-year group, 27 (59%) had a LTR to IFN, resulting in an overall LTR rate of 33% for all patients treated for up to two years (P < 0.001 compared with 3 MU group). Among these 46 subjects, 11 did not complete the full two-year course, including eight who withdrew due to adverse effects. Nine of these 11 patients had received at least 12 months of therapy. All 18 LTR subjects tested (irrespective of treatment group) were serum HCV-RNA negative at the 12-month follow-up evaluation. Improvement in hepatic inflammation was significantly greater among those treated for two years compared with six months, but there was no reduction in fibrosis score in any group. Among the entire study group, treatment duration, liver histology, and liver function (assessed by antipyrine clearance test) were the only independent predictors of ETR, although HCV genotype was closely related to histological severity (eg, cirrhosis was present in 60% of type 1 and 18% of type 3). Viral load and duration of infection were additional predictors of LTR; however, there were insufficient data to determine whether prolonging treatment beyond six months overcomes the negative impact of these predictors. Continuing IFN therapy for at least 12 months decreases the relapse rate by 50% and thereby improves the LTR rate compared with a six-month treatment course. However, our experience of 24 months of treatment indicates that initial IFN treatment courses of this duration are not well tolerated by approximately 20% (8/46) of patients and are unlikely to improve the results obtained with 12-18 months of treatment.

RCT Entities:   Population Interventions Outcomes