Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy
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Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy. / Ferenci, Peter; Scherzer, Thomas-Matthias; Kerschner, Heidrun; Rutter, Karoline; Beinhardt, Sandra; Hofer, Harald; Schöniger-Hekele, Maximilian; Holzmann, Heidemarie; Steindl-Munda, Petra.
in: GASTROENTEROLOGY, Jahrgang 135, Nr. 5, 01.11.2008, S. 1561-7.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy
AU - Ferenci, Peter
AU - Scherzer, Thomas-Matthias
AU - Kerschner, Heidrun
AU - Rutter, Karoline
AU - Beinhardt, Sandra
AU - Hofer, Harald
AU - Schöniger-Hekele, Maximilian
AU - Holzmann, Heidemarie
AU - Steindl-Munda, Petra
PY - 2008/11/1
Y1 - 2008/11/1
N2 - BACKGROUND & AIMS: Oral Silibinin (SIL) is widely used for treatment of hepatitis C, but its efficacy is unclear. Substantially higher doses can be administered intravenously (IV).METHODS: Pedigreed nonresponders to full-dose pegylated (Peg)-interferon/ribavirin (PegIFN/RBV) were studied. First, 16 patients received 10 mg/kg/day SIL IV (Legalon Sil; Madaus, Köln, Germany) for 7 days. In a subsequent dose-finding study, 20 patients received 5, 10, 15, or 20 mg/kg/day SIL for 14 days. In both protocols, PegIFN alpha-2a/RBV were started on day 8. Viral load was determined daily.RESULTS: Unexpectedly, in the first study, HCV-RNA declined on IV SIL by 1.32 +/- 0.55 log (mean +/- SD), P < .001 but increased again in spite of PegIFN/RBV after the infusion period. The viral load decrease was dose dependent (log drop after 7 days SIL: 0.55 +/- 0.5 [5 mg/kg, n = 3], 1.41 +/- 0.59 [10 mg/kg, n = 19], 2.11 +/- 1.34 [15 mg/kg, n = 5], and 3.02 +/- 1.01 [20 mg/kg, n = 9]; P < .001), decreased further after 7 days combined SIL/PegIFN/RBV (1.63 +/- 0.78 [5 mg/kg, n = 3], 4.16 +/- 1.28 [10 mg/kg, n = 3], 3.69 +/- 1.29 [15 mg/kg, n = 5], and 4.85 +/- 0.89 [20 mg/kg, n = 9]; P < .001), and became undetectable in 7 patients on 15 or 20 mg/kg SIL, at week 12. Beside mild gastrointestinal symptoms, IV SIL monotherapy was well tolerated.CONCLUSIONS: IV SIL is well tolerated and shows a substantial antiviral effect against HCV in nonresponders.
AB - BACKGROUND & AIMS: Oral Silibinin (SIL) is widely used for treatment of hepatitis C, but its efficacy is unclear. Substantially higher doses can be administered intravenously (IV).METHODS: Pedigreed nonresponders to full-dose pegylated (Peg)-interferon/ribavirin (PegIFN/RBV) were studied. First, 16 patients received 10 mg/kg/day SIL IV (Legalon Sil; Madaus, Köln, Germany) for 7 days. In a subsequent dose-finding study, 20 patients received 5, 10, 15, or 20 mg/kg/day SIL for 14 days. In both protocols, PegIFN alpha-2a/RBV were started on day 8. Viral load was determined daily.RESULTS: Unexpectedly, in the first study, HCV-RNA declined on IV SIL by 1.32 +/- 0.55 log (mean +/- SD), P < .001 but increased again in spite of PegIFN/RBV after the infusion period. The viral load decrease was dose dependent (log drop after 7 days SIL: 0.55 +/- 0.5 [5 mg/kg, n = 3], 1.41 +/- 0.59 [10 mg/kg, n = 19], 2.11 +/- 1.34 [15 mg/kg, n = 5], and 3.02 +/- 1.01 [20 mg/kg, n = 9]; P < .001), decreased further after 7 days combined SIL/PegIFN/RBV (1.63 +/- 0.78 [5 mg/kg, n = 3], 4.16 +/- 1.28 [10 mg/kg, n = 3], 3.69 +/- 1.29 [15 mg/kg, n = 5], and 4.85 +/- 0.89 [20 mg/kg, n = 9]; P < .001), and became undetectable in 7 patients on 15 or 20 mg/kg SIL, at week 12. Beside mild gastrointestinal symptoms, IV SIL monotherapy was well tolerated.CONCLUSIONS: IV SIL is well tolerated and shows a substantial antiviral effect against HCV in nonresponders.
KW - Antioxidants
KW - Antiviral Agents
KW - Dose-Response Relationship, Drug
KW - Drug Carriers
KW - Drug Resistance, Viral
KW - Drug Therapy, Combination
KW - Female
KW - Follow-Up Studies
KW - Free Radical Scavengers
KW - Hepacivirus
KW - Hepatitis C, Chronic
KW - Humans
KW - Infusions, Intravenous
KW - Interferon-alpha
KW - Male
KW - Middle Aged
KW - Milk Thistle
KW - Polyethylene Glycols
KW - Polymerase Chain Reaction
KW - RNA, Viral
KW - Recombinant Proteins
KW - Ribavirin
KW - Silymarin
KW - Time Factors
KW - Treatment Outcome
KW - Viral Load
U2 - 10.1053/j.gastro.2008.07.072
DO - 10.1053/j.gastro.2008.07.072
M3 - SCORING: Journal article
C2 - 18771667
VL - 135
SP - 1561
EP - 1567
JO - GASTROENTEROLOGY
JF - GASTROENTEROLOGY
SN - 0016-5085
IS - 5
ER -