COMPLETE ERADICATION OF HEPATITIS-C VIRUS AFTER INTERFERON TREATMENT FOR CHRONIC HEPATITIS-C

Background, Alpha-interferon therapy can lead to a persistent biochemi cal response, but discordant opinions have been expressed on the defin ition of sustained response and on the real possibility of complete er adication of hepatitis C virus (HCV). Aims, To define the clinical, vi rological and histologic profiles of the patients with sustained respo nse. Patients, Twenty-eight patients with three different biochemical and virological patterns of response to interferon therapy (16 sustain ed responders, 6 responders with relapse and 6 non responders) were st udied for a follow-up period of 36 months. Methods. HCV-RNA sequences were investigated in serum, peripheral blood mononuclear cells and in liver tissue by means of reverse transcriptase-polymerase chain reacti on, targeted to the 5' non coding region. Viral load in serum was quan tified by branched-DNA signal amplification. HCV genotypes were evalua ted using a line probe assay. Results, All sustained responders showed persistent normal ALT values and loss of serum HCV-RNA during the tre atment and in the entire follow-up period. The HCV clearance was also demonstrated in peripheral blood mononuclear cells and in liver tissue . Pre-treatment HCV-RNA quantitation showed that sustained responders had a significantly lower viral load compared to relapsers and non res ponders (p=0.005). HCV genotyping showed that patients infected by gen otypes 2a, 3a were more likely to achieve a sustained response. Intere stingly, a prolonged response was also observed in the only three pati ents with pre-treatment detectable viral load infected by genotype 3a and in patients with genotype 1b and low viraemia levels. To assess th e histologic outcome following HCV eradication all sustained responder s underwent a second liver biopsy in the follow-up period (6-18 months ). Periportal necrosis and portal inflammation were significantly impr oved. Conclusions, Our results suggest that persistent loss of HCV-RNA in serum, peripheral blood mononuclear cells and liver as well as his tologic improvement are consistent with the complete HCV eradication e ven from intracellular compartments and from potential extra-hepatic s ites of viral persistence. Moreover, pre-treatment viral load HCV infe cting genotypes and histologic features may influence the clinical out come of hepatitis C and the response to interferon therapy.