期刊
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
卷 2, 期 12, 页码 1107-1115出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/S1542-3565(04)00457-4
关键词
-
资金
- National Institutes of Health [RR 00065]
- [K24 DK 02755]
Background & Aims: Insulin resistance and oxidative stress contribute to the pathogenesis of nonalcoholic steatohepatitis (NASH). We conducted a pilot study for the following reasons: (1) to test the hypothesis that a combination of an antioxidant (vitamin E) and an insulin sensitizer (pioglitazone) would be superior to vitamin E alone for the treatment of NASH, and (2) to define the effects of these interventions on insulin-sensitive metabolic functions and correlate the effects with changes in liver histology. Methods: A randomized prospective trial was performed to compare the efficacy and safety of vitamin E alone (400 IU/day) vs. vitamin E (400 IU/day) and pioglitazone (30 mg/day) in nondiabetic, noncirrhotic subjects with NASH. Metabolic functions were assessed by a 2-step, hyperinsulinemic (10 and 40 mU/m(2)/min) euglycemic clamp. Results: A total of 10 patients were randomized to each arm. Two patients on combination therapy discontinued treatment; one because of pregnancy and the other because of hepatotoxicity. Treatment with vitamin E only produced a significant decrease in steatosis (mean grade, 2.2 vs. 1.4; P < .02). Compared with baseline, combination therapy produced a significant decrease in steatosis (mean, 2.3 vs. 1; P < .002), cytologic ballooning (1.3 vs. 0.2; P < .01), Mallory's hyaline (0.7 vs. 0.2; P < .04), and pericellular fibrosis (1.2 vs. 0.6; P < .03). Although vitamin E had no significant effects, combination therapy produced a significant increase in metabolic clearance of glucose and a decrease in fasting free fatty acid (FFA) and insulin. The decrease in fasting FFA and insulin independently predicted improvement in hepatic steatosis and cytologic ballooning. Conclusions: A combination of vitamin E and pioglitazone produces a greater improvement in NASH histology. The improvement in steatosis and cytologic ballooning are related to treatment-associated decreases in fasting FFA and insulin levels.
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