Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis
Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis
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DOI：
10.1053/j.gastro.2008.06.047
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发表时间：
2008-10-01
期刊：
影响因子：
29.4
通讯作者：
Weeber, Jonathan
中科院分区：
文献类型：
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作者：
Aithal, Guruprasad P.;Thomas, James A.;Weeber, Jonathan
背景与目的：非酒精性脂肪性肝炎(NASH)是慢性肝病的主要病因，目前治疗方法有限。噻唑烷二酮的胰岛素增敏、抗炎和抗纤维化特性支持它们用于治疗NASH。我们评估了吡格列酮对非糖尿病NASH患者的治疗作用。方法：我们随机选择74名非糖尿病患者(45名男性，中位年龄54岁)，接受12个月的标准饮食、运动和安慰剂或吡格列酮(30 mg/天)治疗。61名患者(30名安慰剂，31名吡格列酮)在研究开始和结束时都进行了肝活检。结果：与安慰剂相比，吡格列酮治疗组体重增加(平均变化-0.55vs+2.77 kg；P=0.04)，血糖(+0.4vs-0.1 mmol/L；P=0.02)，糖化血红蛋白(+0.16%vs-0.18%；P=0.006)，胰岛素C肽水平(+42vs-78pmol/L；P=0.02)，丙氨酸转氨酶水平(-10.9vs-36.2u/L；P=0.009)、γ-谷氨酰转移酶(-9.4vs-41.2u/L；P=0.002)和铁蛋白(-11.3vs-90.5mg/L；P=0.01)。与安慰剂组相比，接受吡格列酮治疗的患者的肝细胞损伤(P-.005)、Mallory-Denk小体(P=.004)和纤维化(P=.05)等组织学特征减少。结论：非糖尿病NASH患者接受为期12个月的吡格列酮治疗后，代谢和组织学参数得到改善，最显著的是肝损伤和纤维化。有理由进行更大规模的扩展试验，以评估吡格列酮在该患者组中的长期疗效。
Background & Aims: Nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease for which there is limited therapy available. Insulin sensitizing, anti-inflammatory, and antifibrotic properties of thiazolidinediones support their use in treating NASH. We have evaluated pioglitazone in the treatment of nondiabetic patients with NASH. Methods: We randomized 74 nondiabetic patients (45 men; median age, 54 y) with histologically proven NASH to 12 months of standard diet, exercise, and either placebo or pioglitazone (30 mg/day). Sixty-one patients (30 placebo, 31 pioglitazone) had liver biopsies both at the beginning and the end of the study. Results: Compared with placebo, pioglitazone therapy was associated with an increase in weight (mean change, -0.55 vs +2.77 kg; P = .04) and a reduction in glucose (+0.4 vs -0.1 mmol/L; P = .02), HbA1c (+0.16% vs -0.18%; P = .006), insulin C peptide level (+42 vs -78 pmol/L; P = .02), alanine aminotransferase level (-10.9 vs -36.2 u/L; P = .009), gamma-glutamyltransferase level (-9.4 vs -41.2 u/L; P = .002) and ferritin (-11.3 vs -90.5 mu g/L; P = .01). Histologic features including hepatocellular injury (P - .005), Mallory-Denk bodies (P = .004), and fibrosis (P = .05) were reduced in patients treated with pioglitazone compared with those in the placebo group. Conclusions: Pioglitazone therapy over a 12-month period in nondiabetic subjects with NASH resulted in improvements in metabolic and histologic parameters, most notably liver injury and fibrosis. Larger extended trials are justified to assess the long-term efficacy of pioglitazone in this patient group.