Silibinin Is a Potent Antiviral Agent in Patients With Chronic Hepatitis C Not Responding to Pegylated Interferon/Ribavirin Therapy

被引:196
作者
Ferenci, Peter [1 ]
Scherzer, Thomas-Matthias
Kerschner, Heidrun [2 ]
Rutter, Karoline
Beinhardt, Sandra
Hofer, Harald
Schoeniger-Hekele, Maximilian
Holzmann, Heidemarie [2 ]
Steindl-Munda, Petra
机构
[1] Med Univ Vienna, Univ Klin Innere Med 3, AKH, Dept Gastroenterol & Hepatol, A-1090 Vienna, Austria
[2] Med Univ Vienna, Clin Inst Virol, A-1090 Vienna, Austria
关键词
D O I
10.1053/j.gastro.2008.07.072
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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, Koln, 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 S], 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 = 51, and 4.85 0.89 [20 mg/kg, n = 91; 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 weft tolerated and shows a substantial antiviral effect against HCV in nonresponders.
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页码:1561 / 1567
页数:7
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共 29 条
[1]   Silymarin retards collagen accumulation in early and advanced biliary fibrosis secondary to complete bile duct obliteration in rats [J].
Boigk, G ;
Stroedter, L ;
Herbst, H ;
Waldschmidt, J ;
Riecken, EO ;
Schuppan, D .
HEPATOLOGY, 1997, 26 (03) :643-649
[2]  
Cesarone MR, 1999, INT ANGIOL, V18, P127
[3]   Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin [J].
Dehmlow, C ;
Erhard, J ;
deGroot, H .
HEPATOLOGY, 1996, 23 (04) :749-754
[4]   Oxidative stress inhibits IFN-α-induced antiviral gene expression by blocking the JAK-STAT pathway [J].
Di Bona, Danilo ;
Cippitelli, Marco ;
Fionda, Cinzia ;
Camma, Calogero ;
Licata, Anna ;
Santoni, Angela ;
Craxi, Antonio .
JOURNAL OF HEPATOLOGY, 2006, 45 (02) :271-279
[5]   RANDOMIZED CONTROLLED TRIAL OF SILYMARIN TREATMENT IN PATIENTS WITH CIRRHOSIS OF THE LIVER [J].
FERENCI, P ;
DRAGOSICS, B ;
DITTRICH, H ;
FRANK, H ;
BENDA, L ;
LOCHS, H ;
MERYN, S ;
BASE, W ;
SCHNEIDER, B .
JOURNAL OF HEPATOLOGY, 1989, 9 (01) :105-113
[6]   Antioxidant therapy for chronic hepatitis C after failure of interferon: Results of phase II randomized, double-blind placebo controlled clinical trial [J].
Gabbay, Ezra ;
Zigmond, Ehud ;
Pappo, Orit ;
Hemed, Nila ;
Rowe, Mina ;
Zabrecky, George ;
Cohen, Robert ;
Ilan, Yaron .
WORLD JOURNAL OF GASTROENTEROLOGY, 2007, 13 (40) :5317-5323
[7]   Effects of Silybum marianum on serum hepatitis C virus RNA, alanine aminotransferase levels and well-being in patients with chronic hepatitis C [J].
Gordon, A ;
Hobbs, DA ;
Bowden, DS ;
Bailey, MJ ;
Mitchell, J ;
Francis, AJP ;
Roberts, SK .
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 2006, 21 (01) :275-280
[8]   Regulation of arginase II by interferon regulatory factor 3 and the involvement of polyamines in the antiviral response [J].
Grandvaux, N ;
Gaboriau, F ;
Harris, J ;
tenOever, BR ;
Lin, RT ;
Hiscott, J .
FEBS JOURNAL, 2005, 272 (12) :3120-3131
[9]  
HRUBY K, 1983, HUM TOXICOL, V2, P138
[10]   Differential induction of c-fos, c-jun, and apoptosis in lung epithelial cells exposed to ROS or RNS [J].
Janssen, YMW ;
Matalon, S ;
Mossman, BT .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 1997, 273 (04) :L789-L796