A Pilot Study of Vitamin E Versus Vitamin E and Pioglitazone for the Treatment of Nonalcoholic Steatohepatitis
A Pilot Study of Vitamin E Versus Vitamin E and Pioglitazone for the Treatment of Nonalcoholic Steatohepatitis
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DOI：
10.1016/s1542-3565(04)00457-4
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发表时间：
2004-12-01
影响因子：
12.6
通讯作者：
Mills, Alan S.
中科院分区：
文献类型：
--
作者：
Sanyal, Arun J.;Mofrad, Pouneh S.;Mills, Alan S.
背景和目的：胰岛素抵抗和氧化应激导致非酒精性脂肪性肝炎 (NASH) 的发病机制。我们进行了一项初步研究，原因如下：(1) 检验抗氧化剂（维生素 E）和胰岛素增敏剂（吡格列酮）的组合在治疗 NASH 方面优于单独使用维生素 E 的假设，以及 (2) 确定这些干预措施对胰岛素敏感代谢功能的影响，并将这些影响与肝脏组织学的变化相关联。方法：进行一项随机前瞻性试验，比较单独使用维生素 E（400 IU/天）与维生素 E（400 IU/天）和吡格列酮（30 mg/天）在非糖尿病、非肝硬化 NASH 受试者中的疗效和安全性。通过两步高胰岛素（10 和 40 mU/m(2)/min）正常血糖钳夹评估代谢功能。结果：总共 10 名患者被随机分配到每组。两名接受联合治疗的患者停止治疗；一个是因为怀孕，另一个是因为肝毒性。维生素 E 治疗仅显着降低脂肪变性（平均等级，2.2 与 1.4；P < .02）。与基线相比，联合治疗使脂肪变性（平均 2.3 vs. 1；P < .002）、细胞学气球样变（1.3 vs. 0.2；P < .01）、马洛里透明质（0.7 vs. 0.2；P < .04）和细胞周纤维化（1.2 vs. 0.6；P < .03）显着减少。尽管维生素 E 没有显着效果，但联合治疗显着增加了葡萄糖的代谢清除率，并减少了空腹游离脂肪酸 (FFA) 和胰岛素。空腹 FFA 和胰岛素的减少独立预测肝脂肪变性和细胞学气球样变的改善。结论：维生素 E 和吡格列酮的组合可显着改善 NASH 组织学。脂肪变性和细胞气球样变的改善与治疗相关的空腹 FFA 和胰岛素水平降低有关。
Background & Aims: Insulin resistance and oxidative stress contribute to the pathogenesis of nonalcoholic steatohepatitis (NASH). We conducted a pilot study for the following reasons: (1) to test the hypothesis that a combination of an antioxidant (vitamin E) and an insulin sensitizer (pioglitazone) would be superior to vitamin E alone for the treatment of NASH, and (2) to define the effects of these interventions on insulin-sensitive metabolic functions and correlate the effects with changes in liver histology. Methods: A randomized prospective trial was performed to compare the efficacy and safety of vitamin E alone (400 IU/day) vs. vitamin E (400 IU/day) and pioglitazone (30 mg/day) in nondiabetic, noncirrhotic subjects with NASH. Metabolic functions were assessed by a 2-step, hyperinsulinemic (10 and 40 mU/m(2)/min) euglycemic clamp. Results: A total of 10 patients were randomized to each arm. Two patients on combination therapy discontinued treatment; one because of pregnancy and the other because of hepatotoxicity. Treatment with vitamin E only produced a significant decrease in steatosis (mean grade, 2.2 vs. 1.4; P < .02). Compared with baseline, combination therapy produced a significant decrease in steatosis (mean, 2.3 vs. 1; P < .002), cytologic ballooning (1.3 vs. 0.2; P < .01), Mallory's hyaline (0.7 vs. 0.2; P < .04), and pericellular fibrosis (1.2 vs. 0.6; P < .03). Although vitamin E had no significant effects, combination therapy produced a significant increase in metabolic clearance of glucose and a decrease in fasting free fatty acid (FFA) and insulin. The decrease in fasting FFA and insulin independently predicted improvement in hepatic steatosis and cytologic ballooning. Conclusions: A combination of vitamin E and pioglitazone produces a greater improvement in NASH histology. The improvement in steatosis and cytologic ballooning are related to treatment-associated decreases in fasting FFA and insulin levels.