Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL.
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL.
Diabetes Care. 2019 Aug;42(8):1481-1488. doi: 10.2337/dc19-0167. Epub 2019 May 21.
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.
This was a proof-of-concept, randomized, double-blind, placebo-controlled trial conducted from 2010 to 2016. Patients with T2DM and biopsy-proven NASH ( = 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.
More patients on combination therapy achieved the primary outcome versus placebo (54% vs. 19%, = 0.003) but not with vitamin E alone (31% vs. 19%, = 0.26). Both groups showed improvements in resolution of NASH compared with placebo (combination group: 43% vs. 12%, = 0.005; vitamin E alone: 33% vs. 12%, = 0.04). While steatosis assessed by histology improved with combination therapy ( < 0.001) and vitamin E alone ( = 0.018), inflammation ( = 0.018) and ballooning ( = 0.022) only improved with combination therapy. No improvement in fibrosis was observed in any group.
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.
虽然维生素 E 已被证明可改善非酒精性脂肪性肝炎（NASH）患者的病情，但针对 2 型糖尿病（T2DM）患者的相关信息仍有所欠缺。本研究旨在确定维生素 E 单独或联合吡格列酮是否可改善 T2DM 合并 NASH 患者的组织学病变。
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。纳入了 105 例经活检证实患有 T2DM 合并 NASH 的患者，将其随机分配至接受维生素 E 400IU，每日 2 次（b.i.d.）、维生素 E 400IU 联合吡格列酮 45mg/d 或安慰剂治疗。86 例患者完成了 18 个月的研究。主要终点为采用两种不同参数评估的非酒精性脂肪性肝病活动评分降低 2 分，且纤维化无恶化。次要终点为纤维化无恶化情况下 NASH 的缓解、个别组织学评分和代谢参数。
与安慰剂组相比，联合治疗组有更多患者达到了主要终点（54% vs. 19%， = 0.003），但单用维生素 E 组与安慰剂组相比无显著差异（31% vs. 19%， = 0.26）。与安慰剂组相比，两组患者的 NASH 缓解率均有改善（联合治疗组：43% vs. 12%， = 0.005；单用维生素 E 组：33% vs. 12%， = 0.04）。联合治疗组和单用维生素 E 组的组织学评估显示肝内脂肪变均有改善（ < 0.001），炎症（ = 0.018）和气球样变（ = 0.022）也仅在联合治疗组中得到改善。各组的纤维化均无改善。
在本概念验证研究中，与安慰剂相比，联合治疗可更好地改善 T2DM 合并 NASH 患者的肝脏组织学病变。单用维生素 E 并未显著改变主要的组织学结局。
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