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

Journal Article · Tue Jun 10 00:00:00 EDT 2014 · Antiviral Therapy

DOI:https://doi.org/10.3851/imp2806· OSTI ID:1282059

Canini, Laetitia ^[1]; DebRoy, Swati ^[2]; Mariño, Zoe ^[3]; Conway, Jessica M. ^[4]; Crespo, Gonzalo ^[5]; Navasa, Miquel ^[5]; D’Amato, Massimo ^[6]; Ferenci, Peter ^[7]; Cotler, Scott J. ^[8]; Forns, Xavier ^[5]; Perelson, Alan S. ^[4]; Dahari, Harel ^[9]

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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

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 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.

• Research Organization: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
• Sponsoring Organization: USDOE; National Institutes of Health (NIH)
• Grant/Contract Number: AC52-06NA25396; R01-AI07881; P20-GM103452; R01-AI028433; R01-OD011095
• OSTI ID: 1282059
• Journal Information: Antiviral Therapy, Vol. 20, Issue 2; ISSN 1359-6535
• Publisher: International Medical Press
• Country of Publication: United States
• Language: English

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