水飞蓟宾对于对聚乙二醇干扰素/利巴韦林治疗无反应的慢性丙型肝炎患者是一种有效的抗病毒药物。
Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy.
作者信息
Ferenci Peter, Scherzer Thomas-Matthias, Kerschner Heidrun, Rutter Karoline, Beinhardt Sandra, Hofer Harald, Schöniger-Hekele Maximilian, Holzmann Heidemarie, Steindl-Munda Petra
机构信息
Internal Medicine 3, Department of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
出版信息
Gastroenterology. 2008 Nov;135(5):1561-7. doi: 10.1053/j.gastro.2008.07.072. Epub 2008 Aug 3.
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.
背景与目的
口服水飞蓟宾（SIL）被广泛用于丙型肝炎的治疗，但其疗效尚不清楚。静脉注射（IV）时可给予更高剂量。
方法
对全剂量聚乙二醇化（Peg）干扰素/利巴韦林（PegIFN/RBV）治疗无效的纯种患者进行研究。首先，16例患者接受10mg/kg/天的水飞蓟宾静脉注射（Legalon Sil；德国科隆马道斯公司），共7天。在随后的剂量探索研究中，20例患者接受5、10、15或20mg/kg/天的水飞蓟宾治疗14天。在两个方案中，均在第8天开始使用PegIFNα-2a/RBV。每天测定病毒载量。
结果
出乎意料的是，在第一项研究中，静脉注射水飞蓟宾后HCV-RNA下降了1.32±0.55 log（平均值±标准差），P<.001，但在输注期后尽管使用了PegIFN/RBV，病毒载量再次上升。病毒载量下降呈剂量依赖性（水飞蓟宾治疗7天后对数下降：0.55±0.5[5mg/kg，n=3]，1.41±0.59[10mg/kg，n=19]，2.11±1.34[15mg/kg，n=5]，3.02±1.01[20mg/kg，n=9]；P<.001），水飞蓟宾/PegIFN/RBV联合治疗7天后进一步下降（1.63±0.78[5mg/kg，n=3]，4.16±1.28[10mg/kg，n=3]，3.69±1.29[15mg/kg，n=5]，4.85±0.89[20mg/kg，n=9]；P<.001），在第12周时，15或20mg/kg水飞蓟宾治疗的7例患者病毒载量变为不可检测。除了轻微的胃肠道症状外，静脉注射水飞蓟宾单药治疗耐受性良好。
结论
静脉注射水飞蓟宾耐受性良好，对治疗无效的患者显示出显著的抗HCV病毒作用。
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