Year: 2010
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
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.)
Source: New England Journal of Medicine
Institutions: Virginia Commonwealth University, Indiana University Indianapolis, Virginia Mason Medical Center, Case Western Reserve University, Duke University, University of California, San Francisco, Saint Louis University, University of California San Diego, Johns Hopkins University, Washington University in St. Louis, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Eli Lilly and Company, Pfizer, Gilead Sciences, Takeda Pharmaceuticals North America, Teva Pharmaceutical Industries, Pharmavite, Cleveland Clinic, Cleveland Clinic Foundation, University of Washington, Johns Hopkins University, Case Western Reserve University, Virginia Commonwealth University, Saint Louis University, Intercept Pharmaceuticals, Astellas Pharma, Norgine, National Institutes of Health, Genentech, University of California, San Diego, Johns Hopkins Bloomberg School of Public Health, School of Medicine, Indiana University, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: G1154412711, G1171268653, Continuation of the Nonalcoholic Steatohepatitis Clinical Research Network, G1452406238, G1609126075, G1622551803, Clinical and Translational Science Institute, G192442543, G2202404319, Case Western Reserve University/Cleveland Clinic CTSA (UL1), G249129795, G2695549705, General Clinical Research Center, G3062614921, G3775299604, G4462812583, G4488924300, G4524978499, G454469202, G5016624763, G55121285, G5520739208, G5643207399, General Clinical Research Center, G597762487, Patient Oriented Research & Mentoring in liver diseases, G8878559908, General Clinical Research Center, G9000014474, G9000112218, G9000198303, Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN), Collaborative Clinical Research in Nonalcoholic Steatohepatitis
OpenAlex ID: W2062812115