JAMA：乳蓟提取物治疗慢性丙型肝炎没有裨益

芝加哥–据7月18日刊《美国医学会杂志》JAMA上的一项研究披露，使用植物产品水飞蓟素——一种某些病人常常用来治疗慢性肝脏疾病的乳蓟提取物——对那些对治疗有抵抗性的慢性丙型肝炎病毒（HCV）感染的患者而言其裨益并不比安慰剂更多。

慢性丙型肝炎病毒感染影响了全球人口中的近3%，它可能会导致肝硬化、肝功能衰竭及肝癌。有很大比例的患者对这种感染的某些治疗不做出反应，有许多其他的患者则因为并存的疾病而无法得到治疗。根据文章的背景资料：“可改变疾病活性的替代药物可能会有益处。”有33%的罹患HCV感染和肝硬化的病人报告说，他们现在或过去使用过水飞蓟素来治疗他们的疾病。评估乳蓟对各种肝病治疗的临床研究曾经给出了不一致的结果。

北卡罗来纳大学查普希尔分校的Michael W. Fried, M.D.及其同事开展了一项研究，旨在评估用水飞蓟素来治疗慢性HCV的感染。这一多中心的、有安慰剂作为对照的试验是在美国的4家医疗中心内开展的。研究的参与者包括了154名罹患HCV感染且其血清谷丙转氨酶（ALT；一种反映肝功能的酶）浓度为65 U/L或以上，他们在过去所得到的基于干扰素的治疗未获成功。病人加入该研究始于2008年5月并在2010年5月结束，对其的最后随访于2011年3月完成。研究的参与者被随机指派接受每日三次的420-毫克的水飞蓟素、700-毫克的水飞蓟素, 或是匹配的安慰剂，时间共24周。

在治疗结束时，每个治疗组中只有2名参与者达到了预先设定的主要试验终点。达到主要试验终点的参与者百分比在安慰剂组为3.8%，在420-毫克水飞蓟素组为4.0%，在700-毫克水飞蓟素组为3.8%。研究人员还发现，在该研究开始时至治疗结束时对ALT血清浓度的变化进行分析时，在各个治疗组中不存在统计学上的显著差异。此外，在为期24周的治疗中，平均血清HCV RNA浓度没有明显的变化。

对任何一组而言，他们在生活品质评分中的生理或精神健康成分上、在与慢性肝病健康有关的生活品质评估中，或在抑郁症评分中都没有显著的变化。在这些治疗组中，由每个病人所报告的不良反应的频度也没有显著的差异。

文章的作者得出结论：“总之，在过去接受过基于干扰素治疗计划的罹患慢性HCV感染的病人中，口服高于习惯性剂量的水飞蓟素不会显著地改变其疾病活性的生物化学或病毒学的标志。”（生物谷Bioon.com）

doi:10.1001/jama.2012.8265
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Effect of Silymarin (Milk Thistle) on Liver Disease in Patients With Chronic Hepatitis C Unsuccessfully Treated With Interferon Therapy:

Michael W. Fried, MD; Victor J. Navarro, MD; Nezam Afdhal, MD; Steven H. Belle, PhD; Abdus S. Wahed, PhD; Roy L. Hawke, PharmD, PhD; Edward Doo, MD; Catherine M. Meyers, MD; K. Rajender Reddy, MD; for the Silymarin in NASH and C Hepatitis (SyNCH) Study Group

Context 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. Objective 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. Intervention Participants were randomly assigned to receive 420-mg silymarin, 700-mg silymarin, or matching placebo administered 3 times per day for 24 weeks. Main Outcome Measures 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. Results 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. Conclusion 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. Trial Registration clinicaltrials.gov Identifier: NCT00680342