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original article

Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis
Arun J. Sanyal, M.D., NagaChalasani, M.B., B.S., Kris V. Kowdley, M.D., Arthur McCullough, M.D., Anna Mae Diehl, M.D., Nathan M. Bass, M.D., Ph.D., Brent A. Neuschwander-Tetri, M.D., Joel E. Lavine, M.D., Ph.D., JamesTonascia, Ph.D., Aynur Unalp, M.D., Ph.D., Mark Van Natta, M.H.S., Jeanne Clark, M.D., M.P.H., Elizabeth M. Brunt, M.D., David E. Kleiner, M.D., Ph.D., Jay H. Hoofnagle, M.D., and PatriciaR. Robuck, Ph.D., M.P.H., for the NASH CRN*

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Background

Nonalcoholic steatohepatitis is a common liver disease that can progress to cirrho­ sis. Currently, there is noestablished treatment for this disease.
Methods

We randomly assigned 247 adults with nonalcoholic steatohepatitis and without dia­ betes to receive pioglitazone at a dose of 30 mgdaily (80 subjects), vitamin E at a dose of 800 IU daily (84 subjects), or placebo (83 subjects), for 96 weeks. The pri­ mary outcome was an improvement in histologic features of nonalcoholicsteato­ hepatitis, as assessed with the use of a composite of standardized scores for steato­ sis, lobular inflammation, hepatocellular ballooning, and fibrosis. Given the two plannedprimary comparisons, P values of less than 0.025 were considered to indi­ cate statistical significance.
Results

Vitamin E therapy, as compared with placebo, was associated with asignificantly 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 notsignificant (34% and 19%, respectively; P = 0.04). Serum alanine and aspartate aminotransferase levels were reduced with vitamin E and with pio­ glitazone, as compared with placebo (P