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Of the only 3 randomized placebo-controlled trials reported to date, none showed convincing histologic evidence of improvement with any of the investigated medications (antioxidants [vitamins E and C], hepatoprotective agents [ursodeoxycholic acid] or metformin) compared with placebo.76,77,90 Thiazolidinediones improve insulin sensitivity by activating the peroxisome proliferator-activated receptor gamma (PPAR) and have 1 fat girls shown promise in pilot trials involving patients with NASH, although weight gain has been a 1 fat girls troublesome side effect.78,79 In addition, the initial PPAR agonist troglitazone was 1 fat girls withdrawn because of its hepatotoxic effects.91 The second-generation thioglitazones rosiglitazone and pioglitazone appear to be safer, although their use is currently contraindicated in the presence of active liver disease. Both pentoxifylline (a TNF- inhibitor) and atorvastatin (used in NASH patients who have hyperlipidemia) improved aminotransaminase levels in uncontrolled trials, although histologic evidence of their benefit is unknown.92,93,94,95
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