Initial results show NASH improved with vitamin E

Patients on 800 IU of vitamin E daily showed  better liver function and decreased cytologic ballooning

The use of vitamin E supplements by patients with nonalcoholic steatohepatitis was associated with a greater improvement in nonalcoholic fatty liver disease activity scores and cytologic ballooning, compared with the use of pioglitazone of placebo, results from a randomized controlled trial showed.

The investigation was spurred by findings suggesting that oxidative damage and insulin resistance both play a role in the chronic liver diseases, said at the American Association for the Study of Liver Diseases meeting at Virginia Commonwealth University, Richmond, sought to evaluate the role of vitamin E, an antioxidant, and pioglitazone, an insulin-sensitizing agent, in the treatment of nonalcoholic steatohepatitis (NASH).

The 47 patients were randomized to receive 800 IU of vitamin E once daily, 30 mg of pioglitazone once daily, or placebo for 96 weeks. All of the patients had biopsy proven steatohepatitis with a nonalcoholic fatty liver disease (NAFLD) activity score of 4 or higher within 6 months prior to randomization.

The study’s primary end point was improvement — defined as a decrease in NAFLD activity score of 2 points or more and a decrease of at least 1 point in cytologic ballooning — and no worsening of fibrosis. Secondary end points included changes in histologic features, liver enzymes, insulin resistance, anthropometric measures, and quality of life.

Because of the study encompassed two primary comparisons (vitamin E vs. placebo and pioglitazone vs. placebo) “prespecified a significance value for the primary end point,” noting that a P value less than .025 relative to placebo was considered significant.

Compared with placebo, both vitamin E and pioglitazone were associated with liver function improvement, decreased ballooning, and better fibrosis stabilization at 96 weeks, although only vitamin E met the prespecified level of significance for the preliminary end point.

Of the 84 patients randomized to vitamin E, 43% demonstrated the predefined composite improvement, compared with 34% of the pioglitazone group and 19% of the placebo group.

The failure of pioglitazone to meet the end point criteria can likely be attributed to the fact that substantially fewer patients in that group had ballooning at baseline “and therefore couldn’t demonstrate a reduction with treatment.”

Improvement in steatosis as measured by poststudy biopsy, lobular inflammation, ballooning scores, and serum alanine aminotranferase levels were observed in both treatment groups compared with placebo.

Regarding other secondary end points, patients on pioglitazone had greater weight gain (mean 4.7kg) than did those on vitamin E (0.4 kg) or placebo (0.8 kg), but this also was the only group to demonstrate an improvement in insulin resistance. He described that outcome as expected, as previous studies have produced similar results. Neither treatment produced significant changes in quality of life.

Although this study suggests that both vitamin E and pioglitazone can lead to biochemical and histologic improvement in NASH, additional studies are needed to determine not only the sustainability of the observed histological and clinical outcomes, but also the long-term safety of the agents. “With the exception of weight gain, there were no drug-related adverse events, but the study was not powered to assess safety issues.”

That more research is needed. “These are encouraging initial findings. It will be key to have longer-term follow up to determine if either of these therapies prevents the progression of fibrosis to cirrhosis. Studies in other liver diseases have shown improvement in biochemical parameters but failed to stop the progression of the fibrosis.” Vice chancellor for health sciences and dean, UCSD School of Medicine, University of California, San Diego said.

With respect to the vitamin E findings in particular, “this should resurrect our efforts to use antioxidants [for NASH] and, more importantly, to develop very potent antioxidants that are well tolerated in these patients,” AGAF, AASLD president, said. The key is to make sure the vitamin E is of sufficient quality to be effective, because “over-the-counter supplements are mostly unregulated and may vary from product to product,” said the Mount Sinai School of Medicine, New York.