维生素E与维生素E联合吡格列酮治疗非酒精性脂肪性肝炎的初步研究。

A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis.

作者信息

Sanyal Arun J, Mofrad Pouneh S, Contos Melissa J, Sargeant Carol, Luketic Velimir A, Sterling Richard K, Stravitz R Todd, Shiffman Mitchell L, Clore John, Mills Alan S

机构信息

Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Comonwealth University Medical Center, Richmond, VA 23298-0711, USA.

出版信息

Clin Gastroenterol Hepatol. 2004 Dec;2(12):1107-15. doi: 10.1016/s1542-3565(04)00457-4.

DOI:10.1016/s1542-3565(04)00457-4

PMID:15625656

Abstract

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/m2/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.

摘要

背景与目的

胰岛素抵抗和氧化应激参与非酒精性脂肪性肝炎（NASH）的发病机制。我们开展这项初步研究的原因如下：（1）检验抗氧化剂（维生素E）和胰岛素增敏剂（吡格列酮）联合使用在治疗NASH方面优于单独使用维生素E的假设；（2）明确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）联合使用对非糖尿病、非肝硬化NASH患者的疗效和安全性。通过两步高胰岛素血症（10和40 mU/m2/分钟）正常血糖钳夹评估代谢功能。

结果

每组随机分配10例患者。联合治疗组有2例患者停止治疗；1例因妊娠，另1例因肝毒性。仅用维生素E治疗使脂肪变性显著减轻（平均分级，2.2对1.4；P <.02）。与基线相比，联合治疗使脂肪变性（平均，2.3对1；P <.002）、细胞气球样变（1.3对0.2；P <.01）、马洛里透明小体（0.7对0.2；P <.04）和细胞周围纤维化（1.2对0.6；P <.03）显著减轻。虽然维生素E无显著影响，但联合治疗使葡萄糖代谢清除率显著增加，空腹游离脂肪酸（FFA）和胰岛素水平降低。空腹FFA和胰岛素水平降低独立预测肝脂肪变性和细胞气球样变改善。