Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis.
Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis.
复制标题
DOI：
10.1056/nejmoa0907929
复制
发表时间：
2010-05-06
期刊：
影响因子：
--
通讯作者：
NASH CRN
中科院分区：
文献类型：
--
作者：
Sanyal AJ;Chalasani N;Kowdley KV;McCullough A;Diehl AM;Bass NM;Neuschwander-Tetri BA;Lavine JE;Tonascia J;Unalp A;Van Natta M;Clark J;Brunt EM;Kleiner DE;Hoofnagle JH;Robuck PR;NASH CRN
非酒精性脂肪性肝炎是一种常见的肝脏疾病，可进展为肝硬化。目前，对这种疾病没有既定的治疗方法。我们将247名患有非酒精性脂肪性肝炎且无糖尿病的成年人随机分配接受吡格列酮每日30 mg（80名受试者），维生素E每日800 IU（84名受试者）或安慰剂（83名受试者），为期96周。主要结局是非酒精性脂肪性肝炎组织学特征的改善，通过使用脂肪变性、小叶炎症、肝细胞气球样变和纤维化的标准化评分的复合评分进行评估。考虑到两个计划的主要比较，认为P值小于0.025表示具有统计学显著性。与安慰剂相比，维生素E治疗与非酒精性脂肪性肝炎的改善率显著较高相关（43% vs. 19%，P = 0.001），但吡格列酮与安慰剂相比的改善率差异不显著（分别为34%和19%; P = 0.04）。与安慰剂相比，维生素E和吡格列酮可降低血清丙氨酸和天冬氨酸转氨酶水平（两次比较P<0.001），这两种药物都与肝脏脂肪变性的减少有关（维生素E组P = 0.005，吡格列酮组P<0.001）和小叶炎症（维生素E组P = 0.02，吡格列酮组P = 0.004），但纤维化评分未改善（维生素E组P = 0.24，吡格列酮组P = 0.12）。接受吡格列酮的受试者比接受维生素E或安慰剂的受试者体重增加更多;其他副作用的发生率在三组中相似。维生素E治疗非糖尿病成人非酒精性脂肪性肝炎的疗效上级优于安慰剂。对于主要结局，吡格列酮相对于安慰剂没有获益;但是，对于一些次要结局，观察到吡格列酮的显著获益。（ClinicalTrials.gov编号，NCT 00063622。）
Nonalcoholic steatohepatitis is a common liver disease that can progress to cirrhosis. Currently, there is no established treatment for this disease. We randomly assigned 247 adults with nonalcoholic steatohepatitis and without diabetes to receive pioglitazone at a dose of 30 mg daily (80 subjects), vitamin E at a dose of 800 IU daily (84 subjects), or placebo (83 subjects), for 96 weeks. The primary outcome was an improvement in histologic features of nonalcoholic steatohepatitis, as assessed with the use of a composite of standardized scores for steatosis, lobular inflammation, hepatocellular ballooning, and fibrosis. Given the two planned primary comparisons, P values of less than 0.025 were considered to indicate statistical significance. Vitamin E therapy, as compared with placebo, was associated with a significantly higher rate of improvement in nonalcoholic steatohepatitis (43% vs. 19%, P = 0.001), but the difference in the rate of improvement with pioglitazone as compared with placebo was not significant (34% and 19%, respectively; P = 0.04). Serum alanine and aspartate aminotransferase levels were reduced with vitamin E and with pioglitazone, as compared with placebo (P<0.001 for both comparisons), and both agents were associated with reductions in hepatic steatosis (P = 0.005 for vitamin E and P<0.001 for pioglitazone) and lobular inflammation (P = 0.02 for vitamin E and P = 0.004 for pioglitazone) but not with improvement in fibrosis scores (P = 0.24 for vitamin E and P = 0.12 for pioglitazone). Subjects who received pioglitazone gained more weight than did those who received vitamin E or placebo; the rates of other side effects were similar among the three groups. Vitamin E was superior to placebo for the treatment of nonalcoholic steatohepatitis in adults without diabetes. There was no benefit of pioglitazone over placebo for the primary outcome; however, significant benefits of pioglitazone were observed for some of the secondary outcomes. (ClinicalTrials.gov number, NCT00063622.)