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

Abstract

Background & Aims: Intravenous silibinin (SIL) is a potent antiviral agent against hepatitis C virus (HCV) genotype-1. In this 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 usemore » 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. Lastly, 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.« less

Authors:

Dahari, Harel ^[1]; Shteingart, Shimon ^[2]; Gafanovich, Inna ^[3]; Cotler, Scott J. ^[4]; D'Amato, Massimo ^[5]; Pohl, Ralf T. ^[5]; Weiss, Gali ^[6]; Ashkenazi, Yaakov J. ^[7]; Tichler, Thomas ^[7]; Goldin, Eran ^[2]; Lurie, Yoav ^[3]

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+ Show Author Affiliations

1. 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
2. Share'e Zedek Medical Center, Jerusalem (Israel). Digestive Disease Inst.
3. Share'e Zedek Medical Center, Jerusalem (Israel). Digestive Disease Inst., Liver Unit
4. Loyola Univ. Medical Center, Maywood IL (United States). Division of Hepatology
5. Rottapharm Madaus, Monza (Italy)
6. Share'e Zedek Medical Center, Jerusalem (Israel). Nursing Division
7. Share'e Zedek Medical Center, Jerusalem (Israel). Internal medicine

Publication Date:

Fri Oct 10 00:00:00 EDT 2014

Research Org.:

Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Org.:

USDOE; National Institutes of Health (NIH)

OSTI Identifier:

1282055

Alternate Identifier(s):

OSTI ID: 1321740

Report Number(s):

LA-UR-14-23527
Journal ID: ISSN 1478-3223

Grant/Contract Number:  

AC52-06NA25396; R01-AI078881; P20-GM103452

Resource Type:

Accepted Manuscript

Journal Name:

Liver International

Additional Journal Information:

Journal Volume: 35; Journal Issue: 2; Journal ID: ISSN 1478-3223

Publisher:

Wiley

Country of Publication:

United States

Language:

English

Subject:

60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES; hepatitis C; individualized therapy; interferon-free treatment; mathematical modelling; silibinin; sustained virological response; viral kinetics; mathematical modeling