title: Intravenous silibinin as 'rescue treatment' for on-treatment non-responders to pegylated interferon/ribavirin combination therapy.
abstract: BACKGROUND
  Intravenous silibinin (ivSIL) is a potent antiviral agent against HCV. In vitro silibinin (SIL) inhibits viral replication, possibly by inhibiting HCV RNA polymerase. In this proof-of-concept study, ivSIL was tested in on-treatment non-responders to full-dose of pegylated interferon-α2a/ribavirin (standard of care [SOC]).
  
  
  METHODS
  A total of 27 treatment-naive patients with <2 log drop in viral load after 12 weeks or still detectable HCV RNA after 24 weeks of SOC treatment (mean age 54.4 ±6.8 years, male/female 19/8, HCV genotype 1 n=19, 3a n=4 and 4 n=4, liver fibrosis F4 n=14, F3 n=5 and F2 n=3, and interleukin 28B polymorphism C/C n=1, T/C n=22 and T/T n=4) received additionally 20 mg/kg/day SIL (Legalon-SIL(®); Rottapharm-Madaus, Monza, Italy) intravenously for 14 or 21 days. Thereafter, pegylated interferon/ribavirin was continued. HCV RNA was quantified by TaqMan(®) (Roche Diagnostics, Pleasanton, CA, USA).
  
  
  RESULTS
  At the end of ivSIL treatment, 23/27 (85.1%) patients had undetectable HCV RNA. In one of the four remaining patients HCV RNA became undetectable 8 weeks after ivSIL on SOC. Five patients relapsed after ivSIL, three of them responded to repeated administration of ivSIL, but relapsed again. The best predictor of response was a low pre-ivSIL HCV RNA level. A total of 19 patients reached one treatment end point (end of SOC treatment HCV RNA undetectable n=11 and non-response n=8); 8 patients were still on SOC (all HCV-RNA-negative). All 11 patients with end-of-treatment response completed 24 weeks of follow-up; 7 patients remained HCV-RNA-negative and 4 relapsed. Except for a slight increase in bilirubin (mean ±SD 0.98 ±0.35 to 2.12 ±0.99 mg/dl), treatment was well-tolerated.
  
  
  CONCLUSIONS
  ivSIL is an effective 'rescue treatment' for on-treatment non-responders to full-dose of SOC.
authors.affiliation: Department of Internal Medicine 3, Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Karoline
authors.initials: K
authors.lastname: Rutter
authors.forename: Thomas-Matthias
authors.initials: TM
authors.lastname: Scherzer
authors.forename: Sandra
authors.initials: S
authors.lastname: Beinhardt
authors.forename: Heidrun
authors.initials: H
authors.lastname: Kerschner
authors.forename: Albert F
authors.initials: AF
authors.lastname: Stättermayer
authors.forename: Harald
authors.initials: H
authors.lastname: Hofer
authors.forename: Theresia
authors.initials: T
authors.lastname: Popow-Kraupp
authors.forename: Petra
authors.initials: P
authors.lastname: Steindl-Munda
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001317:Austria; D015331:Cohort Studies; D004359:Drug Therapy, Combination / Q000379:methods*; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007275:Injections, Intravenous; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000627:therapeutic use; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012008:Recurrence; D012254:Ribavirin / Q000008:administration & dosage* / Q000627:therapeutic use; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*; D000095022:Interferon Lambda
chemical_list: D000975:Antioxidants; D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; D000077385:Silybin; D012838:Silymarin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a