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Sustained virological response with intravenous silibinin: individualized IFN ‐free therapy via real‐time modelling of HCV kinetics
Author(s) -
Dahari Harel,
Shteingart Shimon,
Gafanovich Inna,
Cotler Scott J.,
D'Amato Massimo,
Pohl Ralf T.,
Weiss Gali,
Ashkenazi Yaakov J.,
Tichler Thomas,
Goldin Eran,
Lurie Yoav
Publication year - 2015
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12692
Subject(s) - medicine , silibinin , ribavirin , adverse effect , hepatitis c virus , hepatitis c , pegylated interferon , antiviral therapy , pharmacology , gastroenterology , immunology , chronic hepatitis , virus
Background & Aims 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 . Methods A 44 year‐old female HCV ‐(genotype‐1)‐infected patient who developed severe psychiatric adverse events to a previous course of peg IFN + 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 . Results 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). Conclusions 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.