Clinical

Vitamin E improves steatohepatitis in kids

Last Updated: 2011-04-26 20:00:17 -0400 (Reuters Health)

By Karla Gale

NEW YORK (Reuters Health) - Vitamin E improves nonalcoholic steatohepatitis (NASH) in children and teens, investigators reported today in JAMA.

"This study buttresses results of our study published last year, in which vitamin E achieved the primary endpoint of improved histopathology in adult NASH," Dr. Joel E. Lavine told Reuters Health.

However, neither vitamin E nor metformin was more effective than placebo in lowering liver enzyme levels in the overall cohort of children with nonalcoholic fatty liver disease (NAFLD).

For the 96 week TONIC trial, Dr. Lavine at Columbia University Medical Center, New York and researchers with the Nonalcoholic Steatohepatitis Clinical Research Network randomly assigned 173 patients, ages 8 to 17, to receive either natural vitamin E (RRR-alpha-tocopherol) 400 IU twice daily (n=58), metformin 500 mg twice daily (n=57), or placebo (n=58).

All of the children had biopsy-confirmed NAFLD and alanine aminotransferase (ALT) levels above 60 U/L. None had diabetes or cirrhosis.

On intent-to-treat analysis, the primary outcome -- a reduction in ALT to no more than 50% of baseline, or no higher than 40 U/L, lasting from the 48th to the 96th week -- was achieved by 26% in the vitamin E group, 16% in the metformin group, and 17% in the placebo group.

From baseline to 96 weeks, ALT fell by a mean of 48.3, 41.7, and 35.2 U/L with vitamin E, metformin, and placebo, respectively. These differences were also nonsignificant, although the p value was 0.07 for vitamin E vs placebo.

Other liver enzymes followed similar patterns in the three groups, Dr. Lavine noted.

But among children with NASH or borderline NASH at baseline, biopsies showed that by 96 weeks the condition had resolved in 25 of 43 kids (58%) in the vitamin E group, compared to 11 of 39 (28%) in the placebo group (p=0.006).

The effect of vitamin E was due primarily to improvements in hepatocellular ballooning, "a major distinguishing feature of NASH," the authors note. Steatosis, inflammation, and fibrosis, on the other hand, did not improve to any significant degree.

Vitamin E also significantly reduced the NAFLD activity score. On a scale of 0 to 8, with higher scores indicating more severe disease, the mean score fell by 1.8 points with vitamin E and 0.7 points with placebo (p=0.02).

Metformin, on the other hand, had no significant effect on NASH resolution or other individual measure except for hepatocellular ballooning.

About 5% to 10% of kids have NAFLD, Dr. Lavine said. He advises doctors to screen kids by ultrasound, computed tomography, or magnetic resonance imaging when they are overweight or obese, or when they have type 2 diabetes, lipid disorders, unexplained elevations in serum ALT, or a family history of unexplained liver disease.

In the "appropriate clinical context" -- no excessive alcohol use, medications or autoimmune disease that can cause fatty liver disease -liver biopsy can be used to diagnose NASH, he said.

In his own practice, Dr. Lavine treats patients with NASH or borderline NASH with vitamin E. The problem is, "liver biopsy is not the standard of care for patients with NAFLD," and no one knows if the risk of biopsy outweighs the benefits of treatment.

So for right now, the recommended management of these patients remains dietary modification and exercise.

Dr. Lavine says pilot studies have shown that other agents may also be effective in NAFLD and NASH, and the Nonalcoholic Steatohepatitis Clinical Research Network is "in discussions with a pharmaceutical partner" to start testing those agents clinically.

The TONIC study was funded by grants from the National Institutes of Health.

SOURCE: http://bit.ly/fw67jo

JAMA 2011;305:1659-1668.