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 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. 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.
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 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. 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.
Authors: Stefan Zeuzem; Jean-Michel Pawlotsky; Esther Lukasiewicz; Michael von Wagner; Ioannis Goulis; Yoav Lurie; Elia Gianfranco; Jan-Maarten Vrolijk; Juan I Esteban; Christophe Hezode; Martin Lagging; Francesco Negro; Alexandre Soulier; Elke Verheij-Hart; Bettina Hansen; Ronen Tal; Carlo Ferrari; Solko W Schalm; Avidan U Neumann Journal: J Hepatol Date: 2005-08 Impact factor: 25.083
Authors: B A Payer; T Reiberger; K Rutter; S Beinhardt; A F Staettermayer; M Peck-Radosavljevic; P Ferenci Journal: J Clin Virol Date: 2010-08-14 Impact factor: 3.168
Authors: E Snoeck; P Chanu; M Lavielle; P Jacqmin; E N Jonsson; K Jorga; T Goggin; J Grippo; N L Jumbe; N Frey Journal: Clin Pharmacol Ther Date: 2010-05-12 Impact factor: 6.875
Authors: Chihiro Morishima; Margaret C Shuhart; Chia C Wang; Denise M Paschal; Minjun C Apodaca; Yanze Liu; Derek D Sloan; Tyler N Graf; Nicholas H Oberlies; David Y-W Lee; Keith R Jerome; Stephen J Polyak Journal: Gastroenterology Date: 2009-09-24 Impact factor: 22.682
Authors: Evan Gorstein; Marianne Martinello; Alexander Churkin; Swikriti Dasgupta; Kevin Walsh; Tanya L Applegate; David Yardeni; Ohad Etzion; Susan L Uprichard; Danny Barash; Scott J Cotler; Gail V Matthews; Harel Dahari Journal: Antiviral Res Date: 2020-06-25 Impact factor: 5.970
Authors: Harel Dahari; Laetitia Canini; Frederik Graw; Susan L Uprichard; Evaldo S A Araújo; Guillaume Penaranda; Emilie Coquet; Laurent Chiche; Aurelie Riso; Christophe Renou; Marc Bourliere; Scott J Cotler; Philippe Halfon Journal: J Hepatol Date: 2016-02-22 Impact factor: 25.083
Authors: S DebRoy; N Hiraga; M Imamura; C N Hayes; S Akamatsu; L Canini; A S Perelson; R T Pohl; S Persiani; S L Uprichard; C Tateno; H Dahari; K Chayama Journal: J Viral Hepat Date: 2016-06-08 Impact factor: 3.728
Authors: Yaakov Hasin; Shimon Shteingart; Harel Dahari; Inna Gafanovich; Sharon Floru; Marius Braun; Amir Shlomai; Anthony Verstandig; Ilana Dery; Susan L Uprichard; Scott J Cotler; Yoav Lurie Journal: World J Hepatol Date: 2016-07-18
Authors: Ashish Goyal; Yoav Lurie; Eric G Meissner; Marian Major; Natasha Sansone; Susan L Uprichard; Scott J Cotler; Harel Dahari Journal: Antiviral Res Date: 2017-06-30 Impact factor: 5.970