Interferon treatment of chronic hepatitis C patients with normal or near normal alanine-amino-transferase levels: might it be harmful rather than useful?

The efficacy of α-interferon (α IFN) in chronic hepatitis C (CHC) with normal or near normal alanine-amino-transferase (ALT) levels is not well known. Aim of this study was to evaluate the biochemical and virological response to α IFN therapy in CHC with persistently normal or near normal ALT levels. Sixteen HCV RNA positive patients affected by biopsy-proven CHC, of whom eight with persistently normal ALT levels and eight with ALT less than 1.5 times the upper reference value, monitored monthly for 6 months before treatment, were treated with recombinant α2b IFN 3 MU/t.i.w. for 6 months. Serum ALT levels were evaluated monthly during and for at least 6 months after the end of treatment. Serum HCV RNA (by nested reverse transcription-polymerase chain reaction (RT-PCR))was tested before, at the end of treatment and at the end of follow-up. HCV genotyping was performed in pretreatment sera, according to the method of Okamoto. Serum HCV RNA titre was evaluated before and at the end of treatment. Of the eight patients with normal ALT, only two (one with genotype 1a and one with 2a) cleared serum HCV RNA and maintained normal ALT levels during treatment and follow-up. All the remaining six patients were persistently HCV-RNA positive: two showed a reduction in HCV RNA titre at the end of therapy, two had no variation and two developed an increase of viraemia; two patients (both with HCV type 1b) had flare-ups during treatment and four (two type 1b, two type 2a) had relapses after the end of treatment. All the eight patients with near normal ALT remained HCV-RNA positive: three showed a reduction in HCV RNA titre, two no variation and three an increase of viraemia at the end of therapy; two patients (both infected with HCV type 1b) had flare-ups during treatment, two maintained ALT levels less than 1.5 times the upper reference limit and four normalized ALT levels during treatment but relapsed after the end of therapy. αIFN treatment induced the clearance of serum HCV RNA only in 2/16 patients; 9/16 patients showed no variation or increase of viraemia at the end of therapy; a flare-up of ALT during therapy or follow-up was frequently observed (8/16). In conclusion, αIFN treatment seems to be of little efficacy for patients with chronic hepatitis C with normal or near normal ALT levels, and may be harmful for those infected with genotype 1b.