Efficacy of atorvastatin for the treatment of nonalcoholic steatohepatitis with dyslipidemia
Efficacy of atorvastatin for the treatment of nonalcoholic steatohepatitis with dyslipidemia
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DOI：
10.1016/j.metabol.2008.07.030
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发表时间：
2008-12-01
影响因子：
9.8
通讯作者：
Chayama, Kazuaki
中科院分区：
文献类型：
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作者：
Hyogo, Hideyuki;Tazuma, Susumu;Chayama, Kazuaki
非酒精性脂肪性肝炎（NASH）是代谢综合征的肝脏表现。目前，NASH还没有确定的治疗方法。本研究的目的是评估阿托伐他汀治疗伴有高脂血症的NASH的疗效。这项前瞻性研究包括31例活检证实的NASH合并高脂血症患者。在阿托伐他汀（每日10mg） 24个月的开放标签研究期间，定期测量体重指数、血脂、肝功能测试、纤维化标志物和脂肪细胞因子（脂联素、瘦素、肿瘤坏死因子-a）。在治疗期间继续进行标准的减肥咨询。治疗前后分别进行口服糖耐量试验和肝脏ct密度测定。17例患者进行了随访肝活检。所有31例患者在基线时都有高胆固醇水平，20例患者也有高甘油三酯水平。在治疗期间，体重指数和血糖水平没有变化。治疗后转氨酶正常23例（74.2%）。脂联素水平显著升高，肿瘤坏死因子-a水平显著升高。显著降低。然而，瘦素水平没有明显变化。长链脂肪酸浓度降低；C18:2,n-6（亚油酸，-21%）和C20:4，n-6（花生四烯酸，-22%）显著降低。肝脂肪变性和非酒精性脂肪肝活动度评分明显改善，而4例患者纤维化分期增加。nash相关代谢参数随着治疗而改善，包括一些患者的纤维化。然而，17例患者中有4例在2年期间纤维化进展，其中3例进展到3期。目前尚不清楚这种不同的反应是否代表抽样误差、人群异质性或未经治疗的餐后高甘油血症。需要进行对照试验来进一步调查和解决这一问题。(C) 2008爱思唯尔公司版权所有。
Nonalcoholic steatohepatitis (NASH) is the hepatic manifestation of the metabolic syndrome. Currently, there is no established therapy for NASH. The aim of the present study was to evaluate the efficacy of atorvastatin in the treatment of NASH associated with hyperlipidemia. This prospective study included 31 patients with biopsy-proven NASH with hyperlipidemia. Body mass index, serum lipids, liver function tests, fibrosis markers, and adipocytokines (adiponectin, leptin, tumor necrosis factor-a) were measured periodically during an open-label study of atorvastatin (10 mg daily) for 24 months. Standard weight-loss counseling was continued during the treatment period. Oral glucose tolerance test and liver density assessed by computerized tomography were performed before and after treatment. Follow-up liver biopsy was performed in 17 patients. All 31 patients had high cholesterol levels at baseline, and 20 also presented high triglyceride levels. The body mass index and serum glucose levels did not change during the treatment. After treatment, 23 patients (74.2%) presented normal transaminase levels. Adiponectin levels were significantly increased, and the levels of tumor necrosis factor-a. were significantly decreased. However, leptin levels were not changed significantly. The concentration of long-chain fatty acids was decreased; and significant decreases were observed in C18:2,n-6 (linoleic acid, -21%) and C20:4,n-6 (arachidonic acid, -22%). Liver steatosis and nonalcoholic fatty liver disease activity score were significantly improved, whereas 4 patients had increased fibrosis stage. The NASH-related metabolic parameters improved with therapy, including fibrosis in some patients. However, 4 of 17 patients had progression of fibrosis over the 2-year period, with 3 of them progressing to stage 3. It is unclear whether this divergent response represents sampling error, heterogeneity in the population, or untreated postprandial hyperglyceridemia. Controlled trials are needed to further investigate and resolve this. (C) 2008 Elsevier Inc. All rights reserved.