Role of Vitamin E for Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes: A Randomized Controlled Trial
Role of Vitamin E for Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes: A Randomized Controlled Trial
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DOI：
10.2337/dc19-0167
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发表时间：
2019-08-01
期刊：
影响因子：
16.2
通讯作者：
Cusi, Kenneth
中科院分区：
文献类型：
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作者：
Bril, Fernando;Biernacki, Diane M.;Cusi, Kenneth
虽然维生素E已被证明可以改善非糖尿病患者的非酒精性脂肪性肝炎（NASH），但缺乏2型糖尿病（T2 DM）患者的信息。本研究的目的是确定维生素E单独或与吡格列酮联合使用是否能改善T2 DM和NASH患者的组织学。研究设计和方法这是一项概念验证、随机、双盲、安慰剂对照试验，于2010年至2016年进行。T2 DM和活检证实的NASH患者（n = 105）随机接受维生素E 400 IU b.i.d.，维生素E 400国际单位每日两次加吡格列酮45 mg/天或安慰剂。86例患者完成了18个月的研究。主要终点是两个不同参数的非酒精性脂肪性肝病活动性评分降低2分，而纤维化没有恶化。次要结局为NASH消退而无纤维化恶化、个体组织学评分和代谢参数。结果：与安慰剂组相比，联合治疗组有更多的患者达到主要结局（54% vs. 19%，P = 0.003），但维生素E单药组没有达到主要结局（31% vs. 19%，P = 0.26）。与安慰剂组相比，两组均显示NASH消退改善（联合组：43% vs. 12%，P = 0.005;维生素E单药组：33% vs. 12%，P = 0.04）。虽然通过组织学评估的脂肪变性在联合治疗（P < 0.001）和维生素E单独治疗（P = 0.018）中得到改善，但炎症（P = 0.018）和气球样变（P = 0.022）仅在联合治疗中得到改善。在任何组中均未观察到纤维化改善。结论：在这项概念验证研究中，联合治疗在改善NASH和T2 DM患者的肝脏组织学方面优于安慰剂。单独使用维生素E不会显著改变主要组织学结局。
OBJECTIVE While vitamin E has shown to improve nonalcoholic steatohepatitis (NASH) in patients without diabetes, information on patients with type 2 diabetes mellitus (T2DM) is lacking. The aim of this study was to determine whether vitamin E, alone or combined with pioglitazone, improves histology in patients with T2DM and NASH. RESEARCH DESIGN AND METHODS This was a proof-of-concept, randomized, double-blind, placebo-controlled trial conducted from 2010 to 2016. Patients with T2DM and biopsy-proven NASH (n = 105) were randomized to vitamin E 400 IU b.i.d., vitamin E 400 IU b.i.d. plus pioglitazone 45 mg/day, or placebo. Eighty-six patients completed the 18-month study. The primary end point was a two-point reduction in the nonalcoholic fatty liver disease activity score from two different parameters, without worsening of fibrosis. Secondary outcomes were resolution of NASH without worsening of fibrosis, individual histological scores, and metabolic parameters. RESULTS More patients on combination therapy achieved the primary outcome versus placebo (54% vs. 19%, P = 0.003) but not with vitamin E alone (31% vs. 19%, P = 0.26). Both groups showed improvements in resolution of NASH compared with placebo (combination group: 43% vs. 12%, P = 0.005; vitamin E alone: 33% vs. 12%, P = 0.04). While steatosis assessed by histology improved with combination therapy (P < 0.001) and vitamin E alone (P = 0.018), inflammation (P = 0.018) and ballooning (P = 0.022) only improved with combination therapy. No improvement in fibrosis was observed in any group. CONCLUSIONS In this proof-of-concept study, combination therapy was better than placebo in improving liver histology in patients with NASH and T2DM. Vitamin E alone did not significantly change the primary histological outcome.