Complete eradication of hepatitis C virus after interferon treatment for chronic hepatitis C

Background, Alpha-interferon therapy can lead to a persistent biochemical response, but discordant opinions have been expressed on the definition of sustained response and on the real possibility of complete eradication of hepatitis C virus (HCV). Aims, To define the clinical, virological and histologic profiles of the patients with sustained response. Patients, Twenty-eight patients with three different biochemical and virological patterns of response to interferon therapy (16 sustained responders, 6 responders with relapse and 6 non responders) were studied 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 reaction, targeted to the 5' non coding region. Viral load in serum was quantified by branched-DNA signal amplification. HCV genotypes were evaluated using a line probe assay. Results, All sustained responders showed persistent normal ALT values and loss of serum HCV-RNA during the treatment 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 responders (p=0.005). HCV genotyping showed that patients infected by genotypes 2a, 3a were more likely to achieve a sustained response. Interestingly, a prolonged response was also observed in the only three patients with pre-treatment detectable viral load infected by genotype 3a and in patients with genotype 1b and low viraemia levels. To assess the histologic outcome following HCV eradication all sustained responders underwent a second liver biopsy in the follow-up period (6-18 months). Periportal necrosis and portal inflammation were significantly improved. Conclusions, Our results suggest that persistent loss of HCV-RNA in serum, peripheral blood mononuclear cells and liver as well as histologic improvement are consistent with the complete HCV eradication even from intracellular compartments and from potential extra-hepatic sites of viral persistence. Moreover, pre-treatment viral load HCV infecting genotypes and histologic features may influence the clinical outcome of hepatitis C and the response to interferon therapy.