Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: A randomized controlled trial
Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: A randomized controlled trial
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DOI：
10.1016/j.freeradbiomed.2012.02.008
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发表时间：
2012-05-01
影响因子：
7.4
通讯作者：
Federico, Alessandro
中科院分区：
文献类型：
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作者：
Loguercio, Carmela;Andreone, Pietro;Federico, Alessandro
目前唯一推荐的非酒精性脂肪肝（NAFLD）治疗方法是改变生活方式。水飞蓟宾的初步研究显示对肝功能有益。 Realsil (RA) 包含与维生素 E 共同配制的水飞蓟素磷脂复合物（水飞蓟宾加磷脂酰胆碱）。我们报告了一项多中心、III 期、双盲临床试验，以评估组织学记录的 NAFLD 患者的 RA。患者按 1:1 的比例随机分配至 RA 组或安慰剂 (P) 组，每天口服两次，持续 12 个月。预先设定的主要结局是随着时间的推移临床状况的改善、血浆肝酶水平的正常化以及超声肝脂肪变性、稳态模型评估（HOMA）和生活质量的改善。次要结局是肝脏组织学评分的改善和/或 NAFLD 评分的降低，但纤维化没有恶化，血浆细胞因子、铁蛋白和肝纤维化标志物也没有变化。我们治疗了 179 名 NAFLD 患者； 36 人也呈 HCV 阳性。 41 名患者提前退出，每个方案分析了 138 名患者（每组 69 名）。除脂肪变性、门静脉浸润和纤维化外，各组之间的基线患者特征总体上平衡良好。不良事件（AE）通常是短暂的，包括腹泻、味觉障碍和瘙痒；没有记录到严重的 AE。接受 RA 但未接受 P 治疗的患者在血浆肝酶水平、HOMA 和肝脏组织学方面表现出显着改善。 15% 的 RA 患者体重指数正常化（P 为 2.1%）。 RA 组（而非 P 组）的 HCV 阳性患者显示出纤维发生标记物的改善。这是第一项系统评估 NAFLD 患者水飞蓟宾的研究。 RA 而非 P 治疗 12 个月与肝酶、胰岛素抵抗和肝脏组织学的改善相关，且体重不增加。这些发现值得进一步调查。 (c) 2012 Elsevier Inc. 保留所有权利。
The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with improvement in liver enzymes, insulin resistance, and liver histology, without increases in body weight. These findings warrant further investigation. (c) 2012 Elsevier Inc. All rights reserved.