Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis - PubMed (original) (raw)
Clinical Trial
. 2010 May 6;362(18):1675-85.
doi: 10.1056/NEJMoa0907929. Epub 2010 Apr 28.
Naga Chalasani, Kris V Kowdley, Arthur McCullough, Anna Mae Diehl, Nathan M Bass, Brent A Neuschwander-Tetri, Joel E Lavine, James Tonascia, Aynur Unalp, Mark Van Natta, Jeanne Clark, Elizabeth M Brunt, David E Kleiner, Jay H Hoofnagle, Patricia R Robuck; NASH CRN
Collaborators, Affiliations
- PMID: 20427778
- PMCID: PMC2928471
- DOI: 10.1056/NEJMoa0907929
Clinical Trial
Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis
Arun J Sanyal et al. N Engl J Med. 2010.
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<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, NCT00063622.)
2010 Massachusetts Medical Society
Figures
Figure 1. Screening, Randomization, and Follow-up of Study Subjects
Figure 2. Changes from Baseline in Aminotransferase Levels, Insulin Resistance, and Weight, According to Study Group
Mean values are shown for changes from baseline (the value at follow-up minus the baseline value) in alanine aminotransferase levels, aspartate aminotransferase levels, insulin resistance, and weight among the 83 subjects in the placebo group, 84 subjects in the vitamin E group, and 80 subjects in the pioglitazone group. All available data were included in the calculation of means; data were missing for less than 10% of subjects. Insulin resistance was calculated according to the homeostasis model assessment, with the use of the following formula: (milligrams of glucose per deciliter × microunits of insulin per milliliter) ÷ 405.
Comment in
- Vitamin E for nonalcoholic steatohepatitis: ready for prime time?
Dufour JF. Dufour JF. Hepatology. 2010 Aug;52(2):789-92. doi: 10.1002/hep.23817. Hepatology. 2010. PMID: 20683969 No abstract available. - Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis.
Armstrong MJ, Houlihan DD, Rowe IA. Armstrong MJ, et al. N Engl J Med. 2010 Sep 16;363(12):1185; author reply 1186. doi: 10.1056/NEJMc1006581. N Engl J Med. 2010. PMID: 20843257 No abstract available. - ACP Journal Club: vitamin E, but not pioglitazone, improved nonalcoholic steatohepatitis in nondiabetic patients.
Sanyal AJ. Sanyal AJ. Ann Intern Med. 2010 Sep 21;153(6):JC3-12. doi: 10.7326/0003-4819-153-6-201009210-02012. Ann Intern Med. 2010. PMID: 20855789 No abstract available. - Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis.
Violi F, Cangemi R. Violi F, et al. N Engl J Med. 2010 Sep 16;363(12):1185-6; author reply 1186. doi: 10.1056/NEJMc1006581. N Engl J Med. 2010. PMID: 20857543 No abstract available. - Clinical trial report: treatment of nonalcoholic steatohepatitis with vitamin E.
Bacon BR. Bacon BR. Curr Gastroenterol Rep. 2011 Feb;13(1):1-2. doi: 10.1007/s11894-010-0162-8. Curr Gastroenterol Rep. 2011. PMID: 21107760 No abstract available. - Insulin resistance and oxidative stress: two therapeutic targets in non-alcoholic steatohepatitis.
Voican CS, Perlemuter G. Voican CS, et al. J Hepatol. 2011 Feb;54(2):388-91. doi: 10.1016/j.jhep.2010.07.054. Epub 2010 Nov 10. J Hepatol. 2011. PMID: 21112115 No abstract available. - Nonalcoholic steatohepatitis treatment.
Luong M, Lau GK. Luong M, et al. Gastroenterology. 2011 Sep;141(3):1121-3; discussion 1123. doi: 10.1053/j.gastro.2011.07.012. Epub 2011 Jul 23. Gastroenterology. 2011. PMID: 21791210 No abstract available.
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