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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 ε max) 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, ε max, was significantly (p≤0.032) associated with increasing severity of liver disease (ε max[s.e.]=0.86[0.05], ε max=0.69[0.06] and ε max=0.59[0.1]). The 2nd phase decline slope was not significantly different among groups (mean 1.88±0.15 log 10IU/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 SILmore » might achieve viral suppression in advanced liver disease.« less

Authors:
 [1];  [2];  [3];  [4];  [5];  [5];  [6];  [7];  [8];  [5];  [4];  [9]
  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 Lab. (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:
Journal Article: 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.
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. doi:10.3851/imp2806.
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. doi:10.3851/imp2806. https://www.osti.gov/servlets/purl/1282059.
@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},
issn = {1359-6535},
number = 2,
volume = 20,
place = {United States},
year = {2014},
month = {6}
}

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