Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis.

被引：2429

作者：

Sanyal, Arun J. ^{[1
]}

Chalasani, Naga ^{[2
]}

Kowdley, Kris V. ^{[3
]}

McCullough, Arthur ^{[4
]}

Diehl, Anna Mae ^{[5
]}

Bass, Nathan M. ^{[6
]}

Neuschwander-Tetri, Brent A. ^{[7
]}

Lavine, Joel E. ^{[9
]}

Tonascia, James ^{[10
]}

Unalp, Aynur ^{[10
]}

Van Natta, Mark ^{[10
]}

Clark, Jeanne ^{[10
]}

Brunt, Elizabeth M. ^{[8
]}

Kleiner, David E. ^{[11
]}

Hoofnagle, Jay H. ^{[12
]}

Robuck, Patricia R. ^{[12
]}

机构：

[1] Virginia Commonwealth Univ, Richmond, VA 23284 USA

[2] Indiana Univ, Indianapolis, IN 46204 USA

[3] Virginia Mason Med Ctr, Seattle, WA 98101 USA

[4] Case Western Reserve Univ, Cleveland, OH 44106 USA

[5] Duke Univ, Durham, NC USA

[6] Univ Calif San Francisco, San Francisco, CA 94143 USA

[7] St Louis Univ, St Louis, MO 63103 USA

[8] Washington Univ, St Louis, MO 63130 USA

[9] Univ Calif San Diego, San Diego, CA 92103 USA

[10] Johns Hopkins Univ, Baltimore, MD USA

[11] NCI, Bethesda, MD 20892 USA

[12] NIDDKD, Bethesda, MD 20892 USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2010年 / 362卷 / 18期

基金：

美国国家卫生研究院;

关键词：

FATTY LIVER-DISEASE; FOLLOW-UP; METAANALYSIS; VARIABILITY; STEATOSIS; HISTORY; NAFLD;

D O I：

10.1056/NEJMoa0907929

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Nonalcoholic steatohepatitis is a common liver disease that can progress to cirrhosis. Currently, there is no established treatment for this disease. Methods: 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. Results: 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. Conclusions: 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, NCT0063622.) N Engl J Med 2010;362:1675-85.

引用

页码：1675 / 1685

页数：11

共 29 条

[1] The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies [J].