Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis

• Published in: The New England journal of medicine Vol. 362; no. 18; pp. 1675 - 1685
• Main Authors: Sanyal, Arun J, Chalasani, Naga, Kowdley, Kris V, McCullough, Arthur, Diehl, Anna Mae, Bass, Nathan M, Neuschwander-Tetri, Brent A, Lavine, Joel E, Tonascia, James, Unalp, Aynur, Van Natta, Mark, Clark, Jeanne, Brunt, Elizabeth M, Kleiner, David E, Hoofnagle, Jay H, Robuck, Patricia R
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 06.05.2010
• Subjects: Adult; Antioxidants - adverse effects; Antioxidants - therapeutic use; Biological and medical sciences; Chi-Square Distribution; Diabetes; Disease; Double-Blind Method; Drug therapy; Fatty Liver - drug therapy; Fatty Liver - pathology; Fatty Liver - physiopathology; Female; General aspects; Humans; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Insulin Resistance; Intention to Treat Analysis; Liver - pathology; Liver diseases; Male; Medical sciences; Middle Aged; Oxidative stress; Pioglitazone; Thiazolidinediones - adverse effects; Thiazolidinediones - therapeutic use; Transaminases - blood; Vitamin E - adverse effects; Vitamin E - therapeutic use; Weight Gain - drug effects; Medicine; Hypoglycemic agent; Digestive system; Vitamin E; Liver; Pioglitazone; Placebo; Thiazolidinedione derivatives; Steatosis
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa0907929

In this randomized trial comparing vitamin E, pioglitazone, and placebo in adults without diabetes who had nonalcoholic steatohepatitis, vitamin E therapy was associated with a significantly higher rate of improvement in nonalcoholic steatohepatitis than was placebo (43% vs. 19%). Significant benefits of pioglitazone over placebo were shown for some secondary outcomes but not for the primary outcome. In adults who had nonalcoholic steatohepatitis, vitamin E therapy was associated with a significantly higher rate of improvement than was placebo. Significant benefits of pioglitazone over placebo were shown for some secondary outcomes. Nonalcoholic steatohepatitis is a common liver disease that is characterized histologically by hepatic steatosis, lobular inflammation, and hepatocellular ballooning 1 , 2 ; it can progress to cirrhosis in up to 15% of patients. 3 , 4 There is currently no therapy that is of proven benefit for nonalcoholic steatohepatitis. The disease is closely associated with insulin resistance and features of the metabolic syndrome such as obesity, hypertriglyceridemia, and type 2 diabetes. 5 , 6 In addition to insulin resistance, oxidative stress has been implicated as a key factor contributing to hepatic injury in patients with nonalcoholic steatohepatitis. 6 , 7 Thus, both insulin resistance and oxidative stress . . .