Rosiglitazone for nonalcoholic steatohepatitis: One-year results of the randomized placebo-controlled fatty liver improvement with rosiglitazone therapy (FLIRT) trial
Rosiglitazone for nonalcoholic steatohepatitis: One-year results of the randomized placebo-controlled fatty liver improvement with rosiglitazone therapy (FLIRT) trial
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DOI：
10.1053/j.gastro.2008.03.078
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发表时间：
2008-07-01
期刊：
影响因子：
29.4
通讯作者：
Poynard, Thierry
中科院分区：
文献类型：
--
作者：
Ratziu, Vlad;Giral, Philippe;Poynard, Thierry
背景与目的：非酒精性脂肪性肝炎（NASH）是一种使胰岛素抵抗状态复杂化的肝脏疾病。这项试验测试了胰岛素增敏剂罗格列酮在NASH患者中的疗效和安全性。研究方法：63例经组织学证实的NASH患者被随机分配接受罗格列酮（第一个月4 mg/天，之后8 mg/天; n = 32）或安慰剂（n = 31）治疗1年。在治疗结束时进行肝活检。终点为脂肪变性的组织学评分改善、血清转氨酶水平正常化以及坏死性炎症和纤维化的改善。结果如下：罗格列酮治疗组比安慰剂组有更多的患者脂肪变性改善（47%比16%; P = 0.014）和转氨酶水平正常化（38%比7%; P = 0.005），尽管只有一半的患者有反应。其他组织学病变（包括纤维化）和活动性综合评分（非酒精性脂肪肝活动性评分）没有改善。脂肪变性的改善与转氨酶水平的降低（r = 0.36; P < .005）、胰岛素敏感性的改善（r = 0.34; P = .008）和脂联素水平的增加（r = -0.4; P < .01）相关，但与体重变化无关。反应的独立预测因子是罗格列酮治疗、无糖尿病和大量脂肪变性。体重增加是主要的不良反应（罗格列酮组平均增加1.5 kg，安慰剂组平均增加-1 kg; P <0.01），腿部疼痛肿胀是剂量减少/停药的主要原因。血清血红蛋白水平轻微但显著降低。无肝毒性。结论：在NASH患者中，罗格列酮改善脂肪变性和转氨酶水平，尽管体重增加，这一作用与胰岛素敏感性改善有关。然而，肝损伤的其他参数没有改善。
Background & Aims: Nonalcoholic steatohepatitis (NASH) is a liver disease that complicates insulin-resistant states. This trial tested the efficacy and safety of rosiglitazone, an insulin-sensitizing agent, in patients with NASH. Methods: Sixty-three patients with histologically proven NASH were randomly assigned to receive rosiglitazone (4 mg/day for the first month and 8 mg/day thereafter; n = 32) or placebo (n = 31) for 1 year. Liver biopsy was performed at the end of treatment. End points were improvement in the histologic score of steatosis, normalization of serum transaminase levels, and improvement in necroinflammation and fibrosis. Results: More patients treated with rosiglitazone than receiving placebo had improved steatosis (47% vs 16%; P = .014) and normalized transaminase levels (38% vs 7%; P = .005), although only half of patients responded. There was no improvement in other histologic lesions, including fibrosis, and a composite score of activity, the nonalcoholic fatty liver disease activity score. Improvement of steatosis correlated with reduction of transaminase levels (r = 0.36; P < .005), improvement in insulin sensitivity (r = 0.34; P = .008), and increase in adiponectin levels (r = -0.4; P < .01) but not with weight variations. Independent predictors of response were rosiglitazone treatment, the absence of diabetes, and massive steatosis. Weight gain was the main adverse effect (mean gain of 1.5 kg in the rosiglitazone group vs - 1 kg in the placebo group; P < .01), and painful swollen legs was the main reason for dose reduction/discontinuation. Serum hemoglobin level was slightly but significantly reduced. There was no hepatic toxicity. Conclusions: In patients with NASH, rosiglitazone improves steatosis and transaminase levels despite weight gain, an effect related to an improvement in insulin sensitivity. However, there is no improvement in other parameters of liver injury.