UNC Liver Center, Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC 27599, USA.
JAMA. 2012 Jul 18;308(3):274-82. doi: 10.1001/jama.2012.8265.
The botanical product silymarin, an extract of milk thistle, is commonly used by patients to treat chronic liver disease, despite scant and conflicting evidence of its efficacy.
To determine the effect of silymarin on liver disease activity in patients with chronic hepatitis C virus (HCV) infection unsuccessfully treated with interferon-based therapy.
DESIGN, SETTING, AND PARTICIPANTS: Multicenter, double-blind, placebo-controlled trial conducted at 4 medical centers in the United States. Participants included 154 persons with chronic HCV infection and serum alanine aminotransferase (ALT) levels of 65 U/L or greater who were previously unsuccessfully treated with interferon-based therapy. Enrollment began in May 2008 and was completed in May 2010, with the last follow-up visit completed in March 2011.
Participants were randomly assigned to receive 420-mg silymarin, 700-mg silymarin, or matching placebo administered 3 times per day for 24 weeks.
The primary outcome measure was serum ALT level of 45 U/L or less (considered within the normal range) or less than 65 U/L, provided this was at least a 50% decline from baseline values. Secondary outcomes included changes in ALT levels, HCV RNA levels, and quality-of-life measures.
After 24 weeks of treatment, only 2 participants in each treatment group (P ≥ .99) met the primary outcome measure (3.8% [95% CI, 0.5% to 13.2%] for placebo, 4.0% [95% CI, 0.5% to 13.7%] for 420-mg silymarin, and 3.8% [95% CI, 0.5% to 13.2%] for 700-mg silymarin). The mean decline in serum ALT activity at the end of treatment did not differ significantly (P = .75) across the 3 treatment groups (mean decline, -4.3 [95% CI, -17.3 to 8.7] U/L for placebo, -14.4 [95% CI, -41.6 to 12.7] U/L for 420-mg silymarin, -11.3 [95% CI, -27.9 to 5.4] U/L for 700-mg silymarin); there likewise were no significant differences in HCV RNA levels (mean change, 0.07 [95% CI, -0.05 to 0.18] log10 IU/mL for placebo, -0.03 [95% CI, -0.18 to 0.12] log10 IU/mL for 420-mg silymarin, 0.04 [95% CI, -0.08 to 0.16] log10 IU/mL for 700-mg silymarin; P = .54) or quality-of-life measures. The adverse event profile of silymarin was comparable with that of placebo.
Higher than customary doses of silymarin did not significantly reduce serum ALT levels more than placebo in participants with chronic HCV infection unsuccessfully treated with interferon-based therapy.
clinicaltrials.gov Identifier: NCT00680342.
水飞蓟素是一种从奶蓟草中提取的植物药，常用于治疗慢性肝脏疾病，尽管其疗效的证据很少且相互矛盾。
确定水飞蓟素对干扰素治疗失败的慢性丙型肝炎病毒（HCV）感染患者肝脏疾病活动度的影响。
设计、地点和参与者：在美国 4 家医疗中心进行的多中心、双盲、安慰剂对照试验。参与者包括 154 名慢性 HCV 感染且血清丙氨酸氨基转移酶（ALT）水平为 65 U/L 或更高的患者，这些患者之前接受过干扰素为基础的治疗但不成功。招募于 2008 年 5 月开始，2010 年 5 月完成，最后一次随访于 2011 年 3 月完成。
参与者被随机分配接受 420mg 水飞蓟素、700mg 水飞蓟素或匹配的安慰剂，每天 3 次，持续 24 周。
主要观察指标是血清 ALT 水平为 45 U/L 或更低（认为在正常范围内）或低于 65 U/L，前提是与基线值相比至少下降了 50%。次要结局包括 ALT 水平、HCV RNA 水平和生活质量测量的变化。
治疗 24 周后，安慰剂组（95%CI，0.5%至 13.2%）、420mg 水飞蓟素组（95%CI，0.5%至 13.7%）和 700mg 水飞蓟素组（95%CI，0.5%至 13.2%）各有 2 名参与者符合主要观察指标（P≥.99）。治疗结束时血清 ALT 活性的平均下降在 3 个治疗组之间无显著差异（P=.75）（安慰剂组平均下降-4.3[95%CI，-17.3 至 8.7]U/L，420mg 水飞蓟素组-14.4[95%CI，-41.6 至 12.7]U/L，700mg 水飞蓟素组-11.3[95%CI，-27.9 至 5.4]U/L）；HCV RNA 水平也无显著差异（安慰剂组平均变化 0.07[95%CI，-0.05 至 0.18]log10IU/mL，420mg 水飞蓟素组-0.03[95%CI，-0.18 至 0.12]log10IU/mL，700mg 水飞蓟素组 0.04[95%CI，-0.08 至 0.16]log10IU/mL；P=.54）或生活质量测量。水飞蓟素的不良事件谱与安慰剂相当。
在干扰素治疗失败的慢性 HCV 感染患者中，高于常规剂量的水飞蓟素并没有比安慰剂更显著地降低血清 ALT 水平。
clinicaltrials.gov 标识符：NCT00680342。
