A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis  Arun J. Sanyal, Pouneh S. Mofrad, Melissa J. Contos, Carol Sargeant, Velimir A. Luketic, Richard K. Sterling, R. Todd Stravitz, Mitchell L. Shiffman, John Clore, Alan S. Mills  Clinical Gastroenterology and Hepatology  Volume 2, Issue 12, Pages 1107-1115 (December 2004) DOI: 10.1016/S1542-3565(04)00457-4 Copyright © 2004 American Gastroenterological Association Terms and Conditions

Figure 1 Baseline histologic data. There were no significant differences in the mean ± SD scores for hepatic steatosis, cytologic ballooning, Mallory’s hyaline, or pericellular or portal fibrosis between the 2 treatment groups. Data from all 10 patients from each arm are shown. Clinical Gastroenterology and Hepatology 2004 2, 1107-1115DOI: (10.1016/S1542-3565(04)00457-4) Copyright © 2004 American Gastroenterological Association Terms and Conditions

Figure 2 Histologic findings at baseline and after 6 months of treatment in patients receiving vitamin E. Patients had a significant decrease in hepatic steatosis after 6 months. The decrease in cytologic ballooning and Mallory’s hyaline approached, but did not reach, significance. No significant change was noted in pericellular fibrosis or portal fibrosis. Clinical Gastroenterology and Hepatology 2004 2, 1107-1115DOI: (10.1016/S1542-3565(04)00457-4) Copyright © 2004 American Gastroenterological Association Terms and Conditions

Figure 3 Histologic findings at baseline and after 6 months of treatment in patients receiving both vitamin E and pioglitazone. A significant decrease was noted in steatosis, cytologic ballooning, Mallory’s hyaline, and pericellular fibrosis. No significant change in portal fibrosis was seen. Data for 8 patients who completed the treatment are shown. Clinical Gastroenterology and Hepatology 2004 2, 1107-1115DOI: (10.1016/S1542-3565(04)00457-4) Copyright © 2004 American Gastroenterological Association Terms and Conditions

Figure 4 Comparison of percent change from baseline to end of study between patients receiving vitamin E alone and patients receiving vitamin E and pioglitazone. Combination therapy was superior to vitamin E alone in terms of the change in degree of steatosis. There were no significant differences in the 2 arms when comparing cytologic ballooning, Mallory’s hyaline, pericellular fibrosis, or portal fibrosis. Clinical Gastroenterology and Hepatology 2004 2, 1107-1115DOI: (10.1016/S1542-3565(04)00457-4) Copyright © 2004 American Gastroenterological Association Terms and Conditions

Figure 5 The change in metabolic parameters from baseline to end of treatment with vitamin E alone. There was no significant effect on the glucose infusion rate (GIR) (indicative of the metabolic clearance of glucose) during low-dose insulin infusion, fasting hepatic glucose output (HGO), fasting FFA level, rate of appearance (RA) of glycerol, suppression of fasting FFA by insulin, lipid oxidation rate, or βOHB. Clinical Gastroenterology and Hepatology 2004 2, 1107-1115DOI: (10.1016/S1542-3565(04)00457-4) Copyright © 2004 American Gastroenterological Association Terms and Conditions

Figure 6 The change in metabolic parameters from baseline to end of treatment with vitamin E and pioglitazone (n = 8 patients). Combination therapy resulted in a significant improvement in metabolic clearance of glucose measured by the glucose infusion rate during low-dose insulin infusion, fasting insulin level, and fasting FFA level. Although Ra glycerol also was suppressed, this approached, but did not reach, significance. Although overall fasting lipid oxidation rates did not change significantly from baseline, fasting βOHB decreased significantly. Clinical Gastroenterology and Hepatology 2004 2, 1107-1115DOI: (10.1016/S1542-3565(04)00457-4) Copyright © 2004 American Gastroenterological Association Terms and Conditions