2015年EASL：牛奶蓟可改善脂肪肝，辣椒素从辣椒有助于纤维化

StephenW

                                                                EASL 2015: Milk Thistle May Improve Steatohepatitis, Capsaicin from Chili Peppers Helps Fibrosis                                                               

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                 Details                                                                                Category: Steatosis/NAFLD/NASH                                                                Published on Wednesday, 13 May 2015 00:00                                                        Written by Liz Highleyman               
                                                                                               

Image: Dreamstime

                                       
               
               
                People who used silymarin, derived from the milk thistle plant, experienced a resolution of non-alcoholic steatohepatitis (NASH) and a reduction in liver fibrosis in a randomized, placebo-controlled trial, researchers reported at the European Association for the Study of the Liver (EASL) 50th International Liver Congress last month in Vienna. Another study found that dietary capsaicin, derived from chili peppers, was associated with improvement in mice with artificially induced fibrosis, the precursor to cirrhosis.

        While effective new direct-acting antiviral drugs can now cure most people with hepatitis C and older therapies can suppress hepatitis B indefinitely, managing liver injury resulting from long-term infection, as well as liver damage due to other causes, remains a challenge.
        A number of herbal therapies have been used to treat liver disease, with some -- such milk thistle -- being common across different regional medical traditions. Results from a global survey of people with hepatitis C presented at the Liver Congress showed that almost all respondents had tried herbal remedies either to slow liver disease progression or to ameliorate symptoms (abstract P1239).
        Silymarin for NASH        Wah Kheong Chan from the University of Malaya in Kuala Lumpur and colleagues conducted a randomized, double-blind, placebo-controlled trial to evaluate silymarinfor the treatment of NASH, or liver fat accumulation and inflammation not associated with alcohol use. NASH and its less severe form, non-alcoholic fatty liver disease (NAFLD), rival viral hepatitis and heavy alcohol consumption as a cause of cirrhosis and liver cancer in the U.S.
        Silymarin, derived from the milk thistle plant Silybum marianum, has been shown to have anti-oxidant, anti-inflammatory, and anti-fibrotic properties in laboratory, animal, and human studies.
        This poster presentation included 64 participants with biopsy-confirmed NASH who had completed the study at the time of the interim analysis. More than half were women and the average age was 50 years. A majority had grade 2 (moderate) steatosis and inflammation, followed by stage 1 (mild), with a small number having stage 3 (severe). The average NAFLD activity score -- which incorporates steatosis, inflammation, and swelling or "ballooning" of hepatocytes -- was 5, with two-thirds having scores of 5-8. A majority of participants had absent or mild liver fibrosis (stage F0-F1), but about one-third had advanced (F3) fibrosis.
        Participants were randomly assigned to receive 700 mg silymarin 3 times daily or placebo for 48 weeks, along with counseling about lifestyle factors such as diet and weight loss. Repeat liver biopsies were performed at the end of the study.
        Results

•                 More patients in the silymarin group experienced at least a 30% improvement in their NAFLD activity score after 48 weeks compared to the placebo group (33% vs 21%, respectively), but the difference did not reach statistical significance.
•                 Similar proportions of patients in both groups showed some improvement in their NAFLD activity score (60% vs 59%, not a significant difference).
•                 Participants in both groups experienced significant improvement in NAFLD activity scores (mean -0.733 with silymarin and -0.706 with placebo).
•                 Significantly more patients in the silymarin arm experienced NASH resolution, defined as NAFLD activity score <3, compared to the placebo arm (13% vs 0%, respectively).
•                 About the same proportion of people in both the silymarin and placebo groups saw an improvement in steatosis (23% vs 24%).
•                 Fewer people in the silymarin group experienced improvement in inflammation compared to the placebo group (27% vs 41%), but the difference was not significant.
•                 50% of people in the silymarin group and 35% in the placebo groups saw an improvement in hepatocyte ballooning, again not a significant difference.
•                 Fibrosis scores decreased significantly in the silymarin group (mean -0.367), while there was no notable change in the placebo group (mean +0.147).
•                 A significantly higher proportion of people in the silymarin group showed improvement in their fibrosis score compared to the placebo group (37% vs 15%, respectively).
•                 4 people in the placebo group (12%) developed liver cirrhosis during follow-up, while none in the silymarin group did so.
  

        "A significantly higher percentage of patients experienced NASH resolution and improvement in fibrosis stage after 48 weeks of treatment with silymarin compared to placebo," the researchers concluded.
        Capsaicin for Fibrosis        Chronic hepatitis B or C, heavy alcohol use, and other factors can cause liver fibrosis, or accumulation of collagen and other scar tissue components. Over years or decades this can progress to cirrhosis, in which scar tissue blocks blood circulation and replaces so much functional liver tissue that vital functions are impaired. Though the process is not fully understood, hepatic stellate cells (HSCs) are known to play a key role in fibrosis development and progression.
        Shanna Bitencourt from Vrije Universiteit in Brussels and colleagues evaluated the inhibitory effects of capsaicin as a dietary supplement on HSC activity in mice with artificially induced liver fibrosis.
        Laboratory studies have shown that capsaicin -- the main compound that gives chili peppers their heat -- can affect the activation, proliferation, and migration of HSCs in vitro, the researchers noted as background.
        In this study male Balb/c mice were given capsaicin as a dietary supplement mixed in their chow (0.01%). Some mice were subject to bile duct ligation to simulate cholestasis or bile accumulation, which can lead to fibrosis. Others were exposed to carbon tetrachloride, a chemical sometimes used as a cleaning agent and fire extinguisher that is toxic to the liver. The researchers dissected the mouse livers and isolated and analyzed their HSCs. In addition, freshly isolated HSCs were cultured and exposed to capsaicin for 7 days in vitro.
        Capsaicin partially improved liver damage in the bile duct ligation mice. Dissected livers showed decreased collagen deposition and fewer areas of necrosis (dead tissue), while isolated HSCs showed down-regulation of markers associated with fibrosis.
        Capsaicin inhibited further progression of liver injury in mice with ongoing exposure to carbon tetrachloride. Mice that were fed capsaicin prior to toxin exposure were protected against development of liver injury and up-regulation of fibrosis activation markers. However, capsaicin did not reduce toxin-induced fibrosis that was already established before mice received the supplement. Capsaicin treatment also inhibited autophagic flux, or self-degradation of cells.
        "Dietary capsaicin decreases the severity of liver injury" in mouse bile duct ligation and "hinders fibrogenesis" in the ligation and carbon tetrachloride-induced liver fibrosis models, the researchers summarized.
        "Collectively, these results support that daily dietary consumption of capsaicin has beneficial effects on liver injury, especially on HSC activation," they concluded.
        5/13/15
        References
        WK Chan, NR Nik Mustapha, S Mahadeva, et al. Silymarin for the treatment of non-alcoholic steatohepatitis: interim analysis of a randomized, double-blind, placebo-controlled trial. 2015 International Liver Congress: 50th Annual Meeting of the European Association for the Study of the Liver (EASL). Vienna, April 22-26, 2015. Abstract LP12.
        S Bitencourt, L Stradiot, S Verhulst, et al. Inhibitory effect of dietary capsaicin on liver fibrosis in mice. 2015 International Liver Congress: 50th Annual Meeting of the European Association for the Study of the Liver (EASL). Vienna, April 22-26, 2015. Abstract P0446.
        C Gore, M Peck-Radosavljevic, and B Taylor. Results of a global survey of hepatitis C patients: the impact of infection, the experience of
the patient pathway and the barriers to, and significance of, a cure. 2015 International Liver Congress: 50th Annual Meeting of the European Association for the Study of the Liver (EASL). Vienna, April 22-26, 2015. Abstract P1293.
        Other Sources
        EASL. Herbal remedy derived from milk thistle demonstrates efficacy in non-alcoholic steatohepatitis. Press release. April 23, 2015.
        EASL. Chilli peppers hold promise of preventing liver damage and progression. Press release. April 23, 2015.

StephenW

2015年EASL：牛奶蓟可改善脂肪肝，辣椒素从辣椒有助于纤维化

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详细信息
    类别：脂肪变性/ NAFLD / NASH
    周三公布，2015年00月13日
    撰稿利兹Highleyman

ALT

图片：误。

人谁使用水飞蓟素，从奶蓟植物衍生的，有经验的非酒精性脂肪性肝炎（NASH）和肝纤维化的减少的随机，安慰剂对照试验的分辨率，研究人员报告了在欧洲协会为肝脏研究（EASL）第50届国际肝病会议上月在维也纳举行。另一项研究发现，辣椒素饮食，从辣椒中提取的，是与改善相关的小鼠人工诱发肝纤维化，前体为肝硬化。

而有效的新的直接作用抗病毒药物，现在可以治愈大多数人与丙型肝炎及以上疗法可以抑制乙肝无止境，管理肝损伤的长期感染造成，以及肝功能损害，由于其他原因，仍然是一个挑战。

一些草药疗法已被用于治疗肝脏疾病，一些 - 比如奶蓟 - 是在不同的区域传统医学普遍。结果从人与丙型肝炎的肝国会提出的一项全球调查结果显示，几乎所有受访者曾尝试草药要么延缓肝脏疾病进展或改善症状（抽象P1239）。
水飞蓟素纳什

华Kheong陈马来亚吉隆坡和同事的大学进行了一项随机，双盲，安慰剂对照试验，以评估silymarinfor治疗NASH的，或肝脂肪堆积和炎症不与酒精使用有关。 NASH及其较不严重的形式，非酒精性脂肪肝病（NAFLD），对手病毒性肝炎和酗酒如肝硬化和肝癌在美国一个原因

水飞蓟素，从奶蓟植物水飞蓟衍生，已经显示出具有抗氧化，抗炎，并在实验室中，动物抗纤维化性质，和人类的研究。

这张海报展示包括64与会者谁完成了研究的中期分析时活检证实的NASH。超过一半是女性，平均年龄为50岁。大多数有2级（中度）脂肪变性和炎症，随后阶段1（轻度），用少量的具有阶段3（重度）。平均NAFLD活动分数 - 其中包含脂肪变性，炎症和肿胀或肝细胞的“气球” - 为5，与具有5-8的分​​数三分之二。大多数与会者不得不缺席或轻度肝纤维化（F0阶段-F1），但约有三分之一患有晚期（F3）纤维化。

参与者被随机分配接受700毫克的水飞蓟素，每日3次或安慰剂治疗48周，以及有关的生活方式因素如饮食和减肥辅导。重复肝活检在研究结束时进行。

结果

    更多的患者的水飞蓟素组中经历至少30％的改善其NAFLD的活动分数48周后相比，安慰剂组（33％比21％，），但差异没有达到统计学显着性。
    患者在两组相似的比例显示出一些改善的NAFLD活动评分（60％比59％，而不是一个显著的差异）。
    两组参与者经历了NAFLD活动评分显著的改善（平均-0.733水飞蓟素和-0.706与安慰剂）。
    显著更多患者在水飞蓟素臂经历NASH分辨率，定义为NAFLD活动分数<3，相比于安慰剂组（分别为13％比0％）。
    有关的人在这两个水飞蓟素和安慰剂组相同的比例看到脂肪变性的改善（23％比24％）。
    人少的水飞蓟素组的经验改善炎症较安慰剂组（27％比41％），但差异不显著。
    的人的水飞蓟素组和安慰剂组35％50％看到肝细胞气球的改进，再没有显著差异。
    纤维化评分的水飞蓟素组（平均-0.367）中显著下降，而出现了在安慰剂组没有显着的变化（平均0.147）。
    的人的水飞蓟素组所述的显著较高比例在其纤维化评分显示改善相比安慰剂组（分别为37％比15％）。
    4人在安慰剂组（12％）开发的随访期间肝硬化，而没有水飞蓟素组这样做。

“的患者显著比例更高经历NASH的分辨率和改善肝纤维化阶段48周水飞蓟素治疗与安慰剂相比之后，”研究人员得出结论。
辣椒素纤维化

慢性乙型或丙型肝炎，酗酒，以及其他因素可导致肝纤维化，或胶原蛋白和其它疤痕组织成分的积累。在几年或几十年这可进展为肝硬化，其中疤痕组织块血液循环和替换关键功能受损这么多的功能性肝组织。虽然这个过程是不完全清楚，肝星状细胞（HSC）是已知在纤维化的发生和发展的关键作用。

莎娜Bitencourt从自由大学布鲁塞尔和同事评估辣椒素的抑制作用在小鼠人工诱发肝纤维化对HSC活性的膳食补充剂。

实验室的研究表明，辣椒素 - 主化合物，使辣椒其热 - 可影响在体外的活化，增殖和造血干细胞的迁移，研究人员指出作为背景。

在这项研究中的雄性Balb / c小鼠给予辣椒素作为膳食补充剂混合，在其食物（0.01％）。一些小鼠受到胆管结扎模拟淤积或胆汁积累，这可导致纤维化。更为暴露于四氯化碳，化学有时使用作为清洗剂和灭火器是有毒的肝脏。研究人员在解剖小鼠肝脏和分离和分析他们的造血干细胞。此外，新鲜分离的造血干细胞进行培养并暴露于辣椒素7天的体外。

辣椒素局部改善肝损伤的胆管结扎小鼠。解剖肝脏表现为减少胶原沉积和坏死（死组织）的几个领域，而造血干细胞分离呈下调与纤维化有关的标记。

辣椒素抑制肝损伤的进一步发展在小鼠持续暴露于四氯化碳。该被前毒素暴露馈送辣椒素小鼠免受肝损伤的发展和上调纤维化活化标记。然而，辣椒素没有降低小鼠接受补充之前已经建立的毒素诱导的纤维化。辣椒素治疗也抑制自噬通量，或细胞的自降解。

在小鼠胆管结扎“膳食辣椒素减少肝损伤的严重程度”，并在结扎和四氯化碳诱导的肝纤维化模型“阻碍纤维化”，研究人员总结。

“总的来说，这些结果支持，辣椒素的每日膳食消费对肝损伤的有益作用，特别是对HSC活化，”他们的结论。

15年5月13日

参考

WK陈，聂NR穆斯塔法，S Mahadeva等。水飞蓟素对非酒精性脂肪性肝炎的治疗：一项随机，双盲，安慰剂对照试验的中期分析。 2015年国际肝病会议：欧洲协会为肝脏研究（EASL）的第50届年会。维也纳，4月22日至26日，2015年摘要LP12。

S Bitencourt，L- Stradiot，S费尔哈斯，等。膳食辣椒素对小鼠肝纤维化的抑制作用。 2015年国际肝病会议：欧洲协会为肝脏研究（EASL）的第50届年会。维也纳，4月22日至26日，2015年摘要P0446。

ç戈尔，男啄拉多萨夫列维奇，和B·泰勒。感染的影响，患者国税发通路的经验和障碍，以及意义，治愈：丙肝患者的全球调查结果。 2015年国际肝病会议：欧洲协会为肝脏研究（EASL）的第50届年会。维也纳，4月22日至26日，2015年摘要P1293。

其他来源

EASL。从奶蓟衍生草药演示在非酒精性脂肪性肝炎的疗效。新闻稿。 2015年4月23日。

EASL。辣椒举办预防肝损伤和发展的承诺。新闻稿。 2015年4月23日。

呕卖膏滴

怪事。中医一直认为肝病是必须戒除辛辣的

StephenW

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辣椒素的抑制作用在小鼠, 需要进一步的研究.