Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis.

Multicenter randomized placebo-controlled trial in adults without diabetes and biopsy-confirmed nonalcoholic steatohepatitis. The vitamin E arm randomized 84 participants; mean age was 46.6 years and mean BMI was 34 kg/m^2 at baseline.

Vitamin E (natural form, 800 IU orally once daily as a softgelatin capsule) was administered for 96 weeks. Participants in the vitamin E arm also received a pioglitazone-like placebo as part of the matched regimen.

Vitamin E improved liver histology versus placebo in adults without diabetes with NASH. The primary histologic improvement endpoint was achieved in 43% versus 19% with placebo (P = 0.001; number needed to treat 4.2), and resolution of definite NASH occurred in 36% versus 21% (P = 0.05). Vitamin E also improved steatosis, lobular inflammation, hepatocellular ballooning, and total NAFLD activity score (mean change -1.9 versus -0.5). Insulin resistance and liver enzymes improved, quality-of-life scores did not differ significantly, and weight gain was not a major signal with vitamin E.

Generalizability is limited to adults without diabetes with biopsy-confirmed NASH. Follow-up was 96 weeks and outcomes were based on liver histology rather than long-term clinical endpoints, and the sample size was modest for detecting rare safety events.