Search Menu
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information
Search Scholarly Publications

Title: Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy

Abstract

HCV kinetic analysis and modeling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to εmax) was fit to viral kinetic data. Our results show that baseline viral load and age were significantly associated with the severity of liver disease (p<0.0001). A biphasic viral decline was observed in most patients with a higher first phase decline patients with less severe liver disease. The maximal effectiveness, εmax, was significantly (p≤0.032) associated with increasing severity of liver disease (εmax[s.e.]=0.86[0.05], εmax=0.69[0.06] and εmax=0.59[0.1]). The 2nd phase decline slope was not significantly different among groups (mean 1.88±0.15 log10IU/ml/wk, p=0.75) as was the rate of change of SIL effectiveness (k=2.12/day[standard error, SE=0.18/day]). HCV-infected cell loss rate (δ[SE]=0.62/day[0.05/day]) was high and similar among groups. We conclude that the high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advancedmore » liver disease.« less

Authors:
 [1];  [2];  [3];  [4];  [5];  [5];  [6];  [7];  [8];  [5];  [4];  [9]
+ Show Author Affiliations
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics; Loyola Univ. Medical Center, Maywood, IL (United States). Division of Hepatology, Dept. of Medicine; Univ. of Edinburgh, Scotland (United Kingdom)
  2. Loyola Univ. Medical Center, Maywood, IL (United States). Division of Hepatology, Dept. of Medicine; Univ. of South Carolina-Beaufort, Bluffton, SC (United States)
  3. Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBEREHD) and August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona (Spain)
  4. Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics
  5. Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBEREHD) and August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona (Spain)
  6. Rottapharm, Monza (Italy)
  7. Medical Univ. of Vienna, Vienna (Austria). Dept. of Gastroenterology and Hepatology
  8. Loyola Univ. Medical Center, Maywood, IL (United States). Division of Hepatology, Dept. of Medicine
  9. Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics; Loyola Univ. Medical Center, Maywood, IL (United States). Division of Hepatology, Dept. of Medicine
Publication Date:
Research Org.:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE; National Institutes of Health (NIH)
OSTI Identifier:
1282059
Grant/Contract Number:  
AC52-06NA25396; R01-AI07881; P20-GM103452; R01-AI028433; R01-OD011095
Resource Type:
Accepted Manuscript
Journal Name:
Antiviral Therapy
Additional Journal Information:
Journal Volume: 20; Journal Issue: 2; Journal ID: ISSN 1359-6535
Publisher:
International Medical Press
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Canini, Laetitia, DebRoy, Swati, Mariño, Zoe, Conway, Jessica M., Crespo, Gonzalo, Navasa, Miquel, D’Amato, Massimo, Ferenci, Peter, Cotler, Scott J., Forns, Xavier, Perelson, Alan S., and Dahari, Harel. Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy. United States: N. p., 2014. Web. doi:10.3851/imp2806.
Copy to clipboard
Canini, Laetitia, DebRoy, Swati, Mariño, Zoe, Conway, Jessica M., Crespo, Gonzalo, Navasa, Miquel, D’Amato, Massimo, Ferenci, Peter, Cotler, Scott J., Forns, Xavier, Perelson, Alan S., & Dahari, Harel. Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy. United States. https://doi.org/10.3851/imp2806
Copy to clipboard
Canini, Laetitia, DebRoy, Swati, Mariño, Zoe, Conway, Jessica M., Crespo, Gonzalo, Navasa, Miquel, D’Amato, Massimo, Ferenci, Peter, Cotler, Scott J., Forns, Xavier, Perelson, Alan S., and Dahari, Harel. Tue . "Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy". United States. https://doi.org/10.3851/imp2806. https://www.osti.gov/servlets/purl/1282059.
Copy to clipboard
@article{osti_1282059,
title = {Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy},
author = {Canini, Laetitia and DebRoy, Swati and Mariño, Zoe and Conway, Jessica M. and Crespo, Gonzalo and Navasa, Miquel and D’Amato, Massimo and Ferenci, Peter and Cotler, Scott J. and Forns, Xavier and Perelson, Alan S. and Dahari, Harel},
abstractNote = {HCV kinetic analysis and modeling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to εmax) was fit to viral kinetic data. Our results show that baseline viral load and age were significantly associated with the severity of liver disease (p<0.0001). A biphasic viral decline was observed in most patients with a higher first phase decline patients with less severe liver disease. The maximal effectiveness, εmax, was significantly (p≤0.032) associated with increasing severity of liver disease (εmax[s.e.]=0.86[0.05], εmax=0.69[0.06] and εmax=0.59[0.1]). The 2nd phase decline slope was not significantly different among groups (mean 1.88±0.15 log10IU/ml/wk, p=0.75) as was the rate of change of SIL effectiveness (k=2.12/day[standard error, SE=0.18/day]). HCV-infected cell loss rate (δ[SE]=0.62/day[0.05/day]) was high and similar among groups. We conclude that the high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.},
doi = {10.3851/imp2806},
journal = {Antiviral Therapy},
number = 2,
volume = 20,
place = {United States},
year = {Tue Jun 10 00:00:00 EDT 2014},
month = {Tue Jun 10 00:00:00 EDT 2014}
}
Copy to clipboard
Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.3851/imp2806
Copyright Statement
Other availability
Search WorldCat Search WorldCat to find libraries that may hold this journal
Citation Metrics:
Cited by: 11 works
Citation information provided by
Web of Science
Save / Share:
Export Metadata
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.

Works referencing / citing this record:

Early HCV viral kinetics under DAAs may optimize duration of therapy in patients with compensated cirrhosis
journal, December 2018

  • Gambato, Martina; Canini, Laetitia; Lens, Sabela
  • Liver International, Vol. 39, Issue 5
  • DOI: 10.1111/liv.14014

Ombitasvir/paritaprevir/ritonavir & dasabuvir ± ribavirin following protease inhibitors failure - a prospective multi-centre trial
journal, April 2020

Ombitasvir/Paritaprevir/Ritonavir & Dasabuvir ± Ribavirin following protease inhibitors failure - A Prospective Multi-Centre Trial
posted_content, April 2020

    Sort by:
    [ × clear filter / sort ]

    Similar Records in DOE PAGES and OSTI.GOV collections: