2 YEARS VERSUS 6 MONTHS OF INTERFERON THERAPY FOR CHRONIC HEPATITIS-C

Short-term (end-of-treatment) responses (ETR) to interferon (IFN) ther apy for chronic hepatitis C are encouraging; however, the relapse rate is high, and long-term response is obtained in only 12-25% of patient s. The Australian Hepatitis C Study Group conducted a trial of 230 pat ients that compared the standard 3 MU three times a week six-month cou rse of IFN-alpha(2b) 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 treat ment) 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 treat ment, the overall relapse rate was 71%, and the long-term response (LT R; continued normal aminotransferase until six month follow up) rate d id 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 pati ents treated for up to two years (P < 0.001 compared with 3 MU group). Among these 46 subjects, Il did not complete the full two-year course , including eight who withdrew due to adverse effects. Nine of these 1 1 patients had received at least 12 months of therapy. All 18 LTR subj ects tested (irrespective of treatment group) were serum HCV-RNA negat ive at the 12-month follow-up evaluation. Improvement in hepatic infla mmation was significantly greater among those treated for two years co mpared with six months, but there was no reduction in fibrosis score i n any group. Among the entire study group, treatment duration, liver h istology, and liver function (assessed by antipyrine clearance test) w ere the only independent predictors of ETR, although HCV genotype was closely related to histological severity leg, cirrhosis was present in 60% of type 1 and 18% of type 3). Viral load and duration of infectio n were additional predictors of LTR; however, there were insufficient data to determine whether prolonging treatment beyond six months overc omes the negative impact of these predictors. Continuing IFN therapy f or at least 12 months decreases the relapse rate by 50% and thereby im proves the LTR rate compared with a six-month treatment course. Howeve r, our experience of 24 months of treatment indicates that initial IFN treatment courses of this duration are not well tolerated by approxim ately 20% (8/46) of patients and are unlikely to improve the results o btained with 12-18 months of treatment.