Randomized, controlled trial with IFN-α combined with ribavirin with and without amantadine sulphate in non-responders with chronic hepatitis C

Background/Aims: Efficacy and safety of interferon-α (IFN-α)/ribavirin retreatment with or without amantadine sulphate were evaluated in non-responders with chronic hepatitis C. Methods: Two hundred twenty five consecutive non-responders to previous antiviral treatment(s) with IFN-α alone or in combination with ribavirin or amantadine were treated with IFN-α 2b 5 MU daily for 4 weeks, 5 MU tiw for 20 weeks, followed by 3 MU tiw for additional 24 weeks combined with ribavirin 1000–1200 mg/d. One hundred fifteen of 225 patients were randomized to receive amantadine sulphate 100 mg bid for 48 weeks. Treatment was discontinued in patients with detectable serum hepatitis C virus (HCV)-RNA at treatment week 24. Results: An overall sustained virologic response with undectable serum HCV-RNA levels was observed in 49/225 patients (22%). Patients infected with HCV-genotype non-1 (P<0.001), low viremia (P=0.011) and only one previous antiviral treatment (P=0.032) were more likely to respond to antiviral retreatment. There was a trend towards higher sustained virologic response rates in patients receiving triple retreatment compared with those treated with IFN-α/ribavirin alone (25 versus 18%, P=0.172). Conclusions: The addition of amantadine was well tolerated and led to an improvement of sustained virologic responses compared with retreatment with IFN-α/ribavirin alone, in particular in patients with low baseline viremia.