Silibinin Is a Potent Antiviral Agent in Patients With Chronic Hepatitis C Not Responding to Pegylated Interferon/Ribavirin Therapy
Silibinin Is a Potent Antiviral Agent in Patients With Chronic Hepatitis C Not Responding to Pegylated Interferon/Ribavirin Therapy
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DOI：
10.1053/j.gastro.2008.07.072
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发表时间：
2008-11-01
期刊：
影响因子：
29.4
通讯作者：
Steindl-Munda, Petra
中科院分区：
文献类型：
--
作者：
Ferenci, Peter;Scherzer, Thomas-Matthias;Steindl-Munda, Petra
背景与目的：口服水飞蓟宾（SIL）广泛用于治疗丙型肝炎，但其疗效尚不清楚。实质上更高的剂量可以静脉内（IV）施用。方法：对全剂量聚乙二醇干扰素/利巴韦林（PegIFN/RBV）治疗无效的家系进行研究。首先，16例患者接受10 mg/kg/天SIL IV（Legalon Sil; Madaus，Körgen，德国）给药7天。在随后的剂量探索研究中，20例患者接受5、10、15或20 mg/kg/天SIL治疗14天。在两种方案中，在第8天开始PegIFN α-2a/RBV。每天测定病毒载量。结果如下：出乎意料的是，在第一项研究中，HCV-RNA在IV SIL上下降了1.32 +/- 0.55 log（平均值+/- SD），P <0.001，但在输注期后，尽管使用了PegIFN/RBV，HCV-RNA仍再次升高。病毒载量下降呈剂量依赖性（7天后SIL的对数下降：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]和3.02 +/- 1.01 [20 mg/kg，n = 9];在SIL/PegIFN/RBV联合治疗7天后进一步降低（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]和4.85 ± 0.89 [20 mg/kg，n = 91; P <0.001）。
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