Sustained virological response with intravenous silibinin: individualized IFN-free therapy via real-time modelling of HCV kinetics

Background & AimsIntravenous silibinin (SIL) is a potent antiviral agent against hepatitis C virus (HCV) genotype-1. In this proof of concept case-study we tested: (i) whether interferon-alfa (IFN)-free treatment with SIL plus ribavirin (RBV) can achieve sustained virological response (SVR); (ii) whether SIL is safe and feasible for prolonged duration of treatment and (iii) whether mathematical modelling of early on-treatment HCV kinetics can guide duration of therapy to achieve SVR. MethodsA 44year-old female HCV-(genotype-1)-infected patient who developed severe psychiatric adverse events to a previous course of pegIFN+RBV, initiated combination treatment with 1200mg/day of SIL, 1200mg/day of RBV and 6000u/day vitamin D. Blood samples were collected frequently till week 4, thereafter every 1-12weeks until the end of therapy. The standard biphasic mathematical model with time-varying SIL effectiveness was used to predict the duration of therapy to achieve SVR. ResultsBased on modelling the observed viral kinetics during the first 3weeks of treatment, SVR was predicted to be achieved within 34weeks of therapy. Provided with this information, the patient agreed to complete 34weeks of treatment. IFN-free treatment with SIL+RBV was feasible, safe and achieved SVR (week-33). ConclusionsWe report, for the first time, the use of real-time mathematical modelling of HCV kinetics to individualize duration of IFN-free therapy and to empower a patient to participate in shared decision making regarding length of treatment. SIL-based individualized therapy provides a treatment option for patients who do not respond to or cannot receive other HCV agents and should be further validated.