Background and aims MicroRNA-122 (miR-122) is an important host factor for hepatitis C virus (HCV) and promotes HCV RNA accumulation. Decreased intra-hepatic levels of miR-122 were observed in patients with hepatocellular carcinoma, suggesting a potential role of miR-122 in the development of HCC. Miravirsen targets miR-122 and resulted in a dose dependent and prolonged decrease of HCV RNA levels in chronic hepatitis C patients. The aim of this study was to establish the sustained virological response rate to peginterferon (P) and ribavirin (R) following miravirsen dosing and to assess long-term safety in patients treated with miravirsen. Methods In this multicenter, retrospective follow-up study we included 36 treatment naïve patients with chronic hepatitis C genotype 1 who received five weekly subcutaneous injections with miravirsen or placebo over a 29-day period in a phase 2a study. Patients were offered PR therapy 3 weeks (3 mg/kg group) or 6 weeks (5 or 7 mg/kg group) after completion of miravirsen or placebo dosing. Results PR therapy was started in 14/36 patients of whom 12 had received miravirsen. SVR was achieved in 7/12 patients previously dosed with miravirsen. All patients dosed with 7 mg/kg miravirsen who were subsequently treated with PR achieved SVR. One patient had a prolonged undetectable HCV RNA period from week 14 to week 29 after baseline without subsequent antiviral therapy and relapsed thereafter. None of the patients treated with anti-miR-122 developed HCC or other liver-related complications. Conclusion No long-term safety issues were observed among 27 miravirsen-treated patients. Targeting miR-122 may be an effective and safe treatment strategy for HCV infection and should be investigated in larger clinical trials.

Anti-miRNA treatment, C virus, Hepatitis, MicroRNA's miR-122,
Antiviral Research
Department of Gastroenterology & Hepatology

Van Der Ree, M.H, van der Meer, A.J.P, Bruijne, J, Maan, R, Vliet, A.A, Welzel, K, … Reesink, H.W. (2014). Long-term safety and efficacy of microRNA-targeted therapy in chronic hepatitis C patients. Antiviral Research, 111, 53–59. doi:10.1016/j.antiviral.2014.08.015