AASLD: Milk Thistle No Help in Chronic HCV

StephenW

AASLD: Milk Thistle No Help in Chronic HCV                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 

By Charles  Bankhead, Staff Writer, MedPage Today Published: November 14, 2011 Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

Action Points                                                                            Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal. Explain that neither high-dose or usual-dose milk thistle did not improve serum alanine aminotransferase levels in patients with previously treated chronic HCV infection compared with placebo in a randomized, controlled trial. Note that HCV RNA and quality of life values also did not change in those receiving the milk thistle in a standardized preparation of 15 pills per day.                                                                         SAN FRANCISCO  --  A botanical agent used in the treatment of liver disorders had no detectable effect on hepatitis C virus (HCV) disease activity in comparison with placebo in patients with previously treated chronic disease, results of a randomized trial showed. Patients treated for six months with either of two doses of silymarin had little change in levels of the liver enzyme alanine transaminase (ALT). About 4% of patients in each silymarin arm and in the placebo group met the primary endpoint of a decline in ALT to ≤45 IU or at least a 50% decline from baseline. "Similarly, symptom scores and quality of life measures were unchanged during silymarin treatment," Michael W. Fried, MD, of the University of North Carolina in Chapel Hill, reported here at the American Association for the Study of Liver Diseases meeting. The trial was perhaps the first to use a single, well-described silymarin preparation, and the doses employed in the study were five to seven times higher than customary doses, he added. Silymarin is an extract of milk thistle and has long been used as a treatment for various types of liver disorders. A mixture of flavonolignans, silymarin has demonstrated anti-inflammatory and immunodulatory properties in vitro, as well as activity against the HCV core and virus-associated gene expression. The substance has been evaluated in clinical trials as a therapeutic aid for cirrhosis, alcoholic liver disease, and viral hepatitis. However, the results have been inconsistent. "Previous studies have been confounded by a lack of well-defined efficacy endpoints, inclusion of heterogeneous populations of patients with liver disease, and use of nonstandardized silymarin preparations," said Fried. To address some of the shortcomings of previous clinical studies, the investigators designed a trial to evaluate silymarin as a potential aid in the treatment of chronic HCV that had not responded to interferon-based therapy. All of the 154 patients enrolled at four centers in the U.S. had a history of treatment with interferon-based therapy and had not achieved a sustained virologic response. The patients had quantifiable HCV RNA and a serum ALT ≥65 IU. The silymarin preparation used for the trial is produced in the Netherlands under the brand name Legalon 140 and is approved as a prescription drug in some European and Asian countries. The customary dose is 140 mg three times a day. Eligible patients were randomized to one of two doses of silymarin (420 or 700 mg) or placebo. Patients in the high-dose silymarin arm took five capsules of the botanical agent three times daily. Patients randomized to the standard dose took three silymarin capsules and two placebo capsules three times each day, and patients in the placebo arm took five matching capsules three times daily. The high-dose arm was based on results from a phase I dose-finding trial "in order to provide the highest likelihood of finding a therapeutic benefit," said Fried. The primary endpoint, measured after 24 weeks, was a decline in serum ALT to ≤45 IU (the upper limit of normal) or a decline of at least 50% from baseline and <65 IU (1.5 times the upper limit of normal). The patients were randomized to the three treatment arms. The three groups did not differ with respect to baseline demographic and clinical characteristics. Median age was 55, about 70% were white, about 90% had HCV genotype 1, about a fourth of the patients had evidence of cirrhosis, and 40% to 45% had a history of milk thistle use. Adherence was good, said Fried, as about 90% of the study participants consumed more than 80% of their medication doses. After six months, one person in the placebo group had a serum ALT ≤45 IU, as did two patients in each of the silymarin arms. Additionally, two patients in the placebo and high-dose silymarin groups had at least a 50% decline in baseline ALT to <65 IU, as did one patient in the 420-mg silymarin arm. The proportion of patients who met either definition of the primary endpoint was 3.8% (two of 52) in the placebo group, 4% (two of 50) in the 420-mg silymarin arm, and 3.8% (two of 52) in the high-dose silymarin arm. The three groups also did not differ significantly with respect to the mean change in ALT, change in HCV RNA, or scores on a battery of quality-of-life instruments. A graph of serum ALT levels throughout the six months showed virtually superimposable lines for the three groups. The placebo and silymarin groups also did not differ significantly in their adverse-event profiles. The most common types of adverse events were gastrointestinal, musculoskeletal, dermatologic, infection, and physical injury. Six patients in the 420-mg silymarin arm and five in the 700-mg arm had serious adverse events, compared with one in the placebo group. During the discussion that followed the presentation, Fried expressed doubt that using even higher doses of silymarin might lead to better results, as suggested by a member of the audience. AASLD president T. Jake Liang, MD, said the study is informative because the results showed not only that silymarin performed no better than placebo in a well-controlled clinical trial but also that the substance is not harmful for people who take it for liver conditions. Fried disclosed relationships with Genentech, Tibotec, Vertex, Merck, Abbott, Pharmasset, Anadys, Bristol-Myers Squibb, and GlaxoSmithKline.

Primary source: American Association for the Study of Liver Diseases                                                         Source reference:                                                                                                     Fried MW, et al "A randomized, placebo-controlled trial of oral silymarin (milk thistle) for chronic hepatitis C: final results of the SYNCH multicenter study" AASLD 2011; Abstract 228.

StephenW

肝病学会：水飞蓟没有帮助，慢性丙型肝炎
由查尔斯班克黑德，在职作家，MedPage今天
发布日期：2011年11月14日，
楼Zaleznik大道，博士，副教授医学临床教授，哈佛医学院，波士顿和评语
多萝西卡普托，马，护士，BC - ADM，CDE，护士规划
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    请注意，这项研究是作为一个抽象的出版，并在一次会议上提出的。应考虑这些数据和结论是初步的，直到在同行评审的期刊出版。


    解释，无论是高剂量或常规剂量的水飞蓟没有改善以前治疗慢性丙型肝炎病毒感染在一项随机，对照试验安慰剂相比，患者的血清谷丙转氨酶水平。


    请注意，丙型肝炎病毒RNA和生活质量的价值观也没有改变那些在标准化的每天15丸准备接收奶蓟。

旧金山 - 植物剂，用于治疗肝脏疾病没有丙型肝炎病毒（HCV）的疾病活动性检测的作用，与以前治疗的慢性疾病患者的安慰剂比较的随机试验结果表明。

六个月任两个剂量的水飞蓟素治疗的患者肝酶丙氨酸转氨酶（ALT）水平的变化不大。在每个水飞蓟素组和安慰剂组的病人中，约4％，在ALT下降到≤45 IU或至少从基线下降50％的主要终点。

“同样，症状评分和生活质量的措施不变，水飞蓟素治疗期间，”麦可油油油油炸，北卡罗莱纳大学教堂山分校的医学博士，在这里的美国肝病会议研究协会。

他补充说，审判可能首先使用一个单一的，以及描述的水飞蓟素制剂，并在研究中所采用的剂量分别比习惯的剂量高出五至七倍。

水飞蓟素是奶蓟提取物，长期以来一直被用于各类肝脏疾病的治疗。的flavonolignans混合物，水飞蓟素已表现出对丙型肝炎病毒核心和病毒相关基因表达的抗炎和immunodulatory性能在体外，以及活动。

“以前的研究一直缺乏一个定义良好的疗效终点，列入肝病患者的异类人群，并使用非标准化的水飞蓟素的准备混淆，说：”炒。
为了解决以前的临床研究的一些缺点，研究人员设计了一个试验，以评估水飞蓟素作为一种潜在的援助，在没有对干扰素治疗慢性丙型肝炎的治疗。
所有在四个中心在美国就读的154例患者进行了治疗干扰素治疗的历史，并没有达到持续病毒学应答。患者可量化的HCV RNA和血清ALT≥65 IU。
在荷兰生产的水飞蓟素制剂用于试验的是140的品牌名称利加隆是作为处方药在欧洲和亚洲一些国家批准。习惯剂量为140毫克，每日3次。
符合条件的患者被随机分配到两个剂量的水飞蓟素（420或700毫克）或安慰剂。患者服用高剂量的水飞蓟素臂五个植物园代理胶囊，每日三次。患者随机接受标准剂量了三个水飞蓟素胶囊和安慰剂胶囊，每日3次，和安慰剂组的病人参加了5个配套胶囊，每日三次。
高剂量组的基础上，从一个阶段的结果，我的剂量发现的审判“，以提供最高可能找到治疗效果，说：”炒。
主要终点，24周后测定，在血清ALT下降到≤45 IU（正常值上限）或从基线和<65 IU（正常上限的1.5倍）下降了至少50％。
患者被随机分配到三个治疗武器。三组差异不尊重基线人口统计学和临床​​特征。年龄中位数为55岁，约70％是白人，90％左右，约四分之一的患者HCV基因型1，肝硬化的证据，40％至45％，奶蓟使用的历史。
坚持好，说炒，约90％的消耗超过80％的用药剂量的研究参与者。
半年后，一个人在安慰剂组血清ALT≤45 IU，两名病人一样在每个水飞蓟素武器。此外，在安慰剂组和高剂量的水飞蓟素组患者至少在基线ALT <65 IU下降50％，作为一个病人在420毫克的水飞蓟素臂。
患者谁见了任主要终点的定义的比例是3.8％（52），在安慰剂组，4％（50）420毫克的水飞蓟素臂，和3.8％（52）高剂量的水飞蓟素臂。
三组也没有在ALT的平均变化显著差异，改变在丙型肝炎病毒RNA，或对生活质量的仪器的电池得分。整个六个月的血清ALT水平的图形显示，三组几乎superimposable线。
安慰剂组和水飞蓟素组也没有显著差异，在他们的不良事件概况。不良事件的最常见的类型，胃肠，肌肉骨骼，皮肤病，感染和人身伤害。 6 420毫克的水飞蓟素臂和700毫克的手臂5患者有严重不良事件，与安慰剂组之一相比。
在随后的讨论中的演示文稿，煎，使用更高剂量的水飞蓟素，可能会导致更好的结果，作为观众成员的建议表示怀疑。
肝病学会主席T.杰克梁医师说，这项研究是知识性的，因为结果不仅表明，水飞蓟素的表现丝毫不比良好控制的临床试验中的安慰剂，但该物质是不是有害的人肝条件。

javeping

回复 StephenW 的帖子

这样啊，我的DNA3.68*10的3次方，转安94，还想吃这个降呢，看来又不敢吃了

StephenW

javeping 发表于 2011-11-15 18:56
回复 StephenW 的帖子

这样啊，我的DNA3.68*10的3次方，转安94，还想吃这个降呢，看来又不敢吃了 ...

最好不要服用。更好定期在阳光下运动，服用维生素D，并定期喝一些咖啡

javeping

回复 StephenW 的帖子

抗病毒也不用，医生说的，我想也是，但如果有替诺，俺还是用上个四五年的。比如印度的价格。