Early viral kinetics on treatment with pegylated interferon-alpha-2a in chronic hepatitis C virus genotype 1 infection

Even with pegylated (PEG) interferons (IFN), therapy of chronic hepatitis C (genotype 1) remains unsatisfactory. The initial viral response to IFN identifies patients infected with IFN resistant viruses not responding to standard IFN/ribavirin therapy. The impact of primary IFN unresponsiveness for PEG-IFN-alpha-2a/ribavirin therapy is unknown. Viral load was measured in 22 chronic hepatitis C (genotype 1) patients before and 24 h after 9 MU IFN-alpha-2a (days 0 and 1), and before and during weekly 180 microg PEG-IFN-alpha-2a (days 7, 8, 11, 14 and 21) administration. Thereafter, ribavirin (800 mg/d) was added for 6 months. Virological responders continued treatment for a further 6 months. Twenty-eight patients treated with standard IFN/ribavirin therapy in a previous study using an analogous protocol served as historic controls. After 6 months 15 (68.2%) patients were (HCV-RNA) negative, eight of whom (36.4%) had a sustained response. The decrease in viral load 24 h after 9 MU IFN-alpha-2a was greater in virological responders (1.05 log [0.25-1.67]) than in nonresponders (NR) (0.34 [0.14-0.65]; P=0.003). In contrast, viral decline was not different between responders and NRs during the first 2 weeks on PEG-IFN-alpha-2a. All patients with an initial decline > 1.4 log became sustained responders. Five of 12 patients with a log change < 0.8 became end of treatment responders, two had a sustained response. Antiviral response to PEG-IFN-alpha-2a is different to that on standard IFN. In spite of a lower initial response PEG-IFN-alpha-2a/ribavirin combination therapy may overcome predicted IFN unresponsiveness.