title: Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy.
abstract: BACKGROUND
  HCV kinetic analysis and modelling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in three groups of patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease.
  
  
  METHODS
  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 final effectiveness [εmax]) was fitted to viral kinetic data.
  
  
  RESULTS
  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 in patients with less severe liver disease. The εmax was significantly (P≤0.032) associated with increasing severity of liver disease (non-cirrhotic εmax [se]=0.86 [0.05], compensated cirrhotic εmax=0.69 [0.06] and decompensated cirrhotic εmax=0.59 [0.1]). The second phase decline slope was not significantly different among groups (mean 1.88 ±0.15 log10 IU/ml/week, P=0.75) as was the rate of change of SIL effectiveness (k=2.12/day [se=0.18/day]). HCV-infected cell loss rate (δ [se]=0.62/day [0.05/day]) was high and similar among groups.
  
  
  CONCLUSIONS
  The high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.
authors.affiliation: Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Canini
authors.forename: Swati
authors.initials: S
authors.lastname: DebRoy
authors.forename: Zoe
authors.initials: Z
authors.lastname: Mariño
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Conway
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Crespo
authors.forename: Miquel
authors.initials: M
authors.lastname: Navasa
authors.forename: Massimo
authors.initials: M
authors.lastname: D'Amato
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Cotler
authors.forename: Xavier
authors.initials: X
authors.lastname: Forns
authors.forename: Alan S
authors.initials: AS
authors.lastname: Perelson
authors.forename: Harel
authors.initials: H
authors.lastname: Dahari
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D001682:Biological Availability; D016923:Cell Death / Q000187:drug effects; D003198:Computer Simulation; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology / Q000821:virology; D006801:Humans; D007275:Injections, Intravenous; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D012720:Severity of Illness Index; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019562:Viral Load / Q000187:drug effects
chemical_list: D000975:Antioxidants; D012838:Silymarin; D000077385:Silybin