Sustained virological response with intravenous silibinin: individualized IFN-free therapy via real-time modelling of HCV kinetics
- Loyola Univ. Medical Center, Maywood IL (United States). Division of Hepatology; Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics
- Share'e Zedek Medical Center, Jerusalem (Israel). Digestive Disease Inst.
- Share'e Zedek Medical Center, Jerusalem (Israel). Digestive Disease Inst., Liver Unit
- Loyola Univ. Medical Center, Maywood IL (United States). Division of Hepatology
- Rottapharm Madaus, Monza (Italy)
- Share'e Zedek Medical Center, Jerusalem (Israel). Nursing Division
- Share'e Zedek Medical Center, Jerusalem (Israel). Internal medicine
Providing here our aims and project background, we note that intravenous 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. With our method, a 44 year-old female HCV-(genotype-1)-infected patient who developed severe psychiatric adverse events to a previous course of pegIFN+RBV, initiated combination treatment with 1200 mg/day of SIL, 1200 mg/day of RBV and 6000 u/day vitamin D. Blood samples were collected frequently till week 4, thereafter every 1-12 weeks 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. Our results show that, based on modelling the observed viral kinetics during the first 3 weeks of treatment, SVR was predicted to be achieved within 34 weeks of therapy. Provided with this information, the patient agreed to complete 34 weeks of treatment. IFN-free treatment with SIL+RBV was feasible, safe and achieved SVR (week-33). In conclusion, we 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.
- Research Organization:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Organization:
- USDOE; National Inst. of Health (NIH)
- Grant/Contract Number:
- AC52-06NA25396
- OSTI ID:
- 1282055
- Journal Information:
- Liver International, Journal Name: Liver International Journal Issue: 2 Vol. 35; ISSN 1478-3223
- Publisher:
- WileyCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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