Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis

Authors

Arun J. Sanyal, Virginia Commonwealth UniversityFollow
Naga Chalasani, Indiana University
Kris V. Kowdley, Virginia Mason Medical Center
Arthur McCollough, Case Western Reserve University
Anna Mae Diehl, Duke University
Nathan M. Bass, University of California - San Francisco
Brent A. Neuschwander-Tetri, Saint Louis University
Joel E. Lavine, University of California - San Diego
James Tonascia, Johns Hopkins University
Aynur Unalp, Johns Hopkins University
Mark Van Natta, Johns Hopkins University
Jeanne Clark, Johns Hopkins University
Elizabeth M. Brunt, Washington University in St Louis
David E. Kleiner, National Cancer Institute
Jay H. Hoofnagle, National Institute of Diabetes and Digestive and Kidney Diseases
Patricia R. Robuck, National Institute of Diabetes and Digestive and Kidney Diseases

Document Type

Article

Original Publication Date

2010

Journal/Book/Conference Title

The England Journal of Medicine

Volume

362

DOI of Original Publication

10.1056/NEJMoa0907929

Comments

Originally Published at http://dx.doi.org/10.1056/NEJMoa0907929

Date of Submission

January 2015

Abstract

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

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, NCT00063622.)

Rights

From The New England Journal of Medicine, Sanyal, A. J., Chalasani, N., Kowdley, K. V. et al., Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis, Vol. 362, Page 1675, Copyright © 2010 Massachusetts Medical Society.

Is Part Of

VCU Internal Medicine Publications