AASLD: Vitamin E Resolves NASH in Children
By Kristina Fiore , Staff Writer, MedPage TodayPublished: November 02, 2010Reviewed by Zalman S. Agus, MD; Emeritus Professor University of Pennsylvania School of Medicine.
BOSTON -- Vitamin E may help resolve nonalcoholic steatohepatitis (NASH) in children -- although it won't lower alanine aminotransferase (ALT) levels, researchers reported here.Although the 96-week randomized trial involving nearly 200 children missed its primary endpoint of lowering ALT, only vitamin E -- compared with metformin and placebo -- had significant effects on several histologic parameters, according to Joel Lavine, MD, of Columbia University, and colleagues."Vitamin E use should be supported for children with NASH," Lavine said during an oral presentation at the annual meeting of the American Association for the Study of Liver Diseases.Similar findings were reported for adults last April, in which the PIVENS trial, published in the New England Journal of Medicine, found vitamin E significantly improved a composite of four histological features of NASH compared with placebo.
In that trial, pioglitazone (Actos) also improved these histologic features, but not significantly compared with placebo.
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in American children, yet no pharmacologic therapy has yet been established.
So the researchers conducted a randomized, placebo-controlled trial among 173 children (ages 8 to 17) from eight centers in the NASH Clinical Research Network to see whether vitamin E or metformin would mitigate fatty liver disease.
The kids were randomized to 500 mg of metformin twice a day, 400 IU of vitamin E twice a day, or placebo. The mean age was 13, boys made up the majority of the population (80%); they were largely Hispanic and most were obese with a body mass index (BMI) in the 33 to 34 range, Lavine said.
They had biopsy-confirmed NAFLD, as well as an ALT over 60 at baseline. Those with diabetes, cirrhosis, or significant alcohol use were excluded.
All of the children in the trial were also given standard care, including advice on lifestyle modification.
Children had regular clinic visits during the 96-week trial, and were followed for an additional 24 weeks to assess treatment durability.
The primary endpoint was reduction in ALT, while the secondary endpoints looked at histological changes.
The researchers found that ALT decreased in all three groups -- most likely because they were all receiving the standard of care, which is education on diet and exercise, Lavine said.
There was a more rapid decline in those levels for children on vitamin E, but the data converged by the end of the trial (25.9% achieved a reduction with vitamin E, 15.8% with metformin, and 17.2% with placebo).
The results did not change after controlling for factors such as age, gender, and ethnicity, Lavine said.
Yet when the researchers looked at histological factors, they found that both vitamin E and metformin improved hepatocellular ballooning compared with placebo (44% and 44% versus 21%, P=0.006).
But only vitamin E significantly improved NAFLD scores compared with placebo (P=0.02).
In the subset of children with NASH at baseline, vitamin E significantly increased resolution of NASH on the 96 week liver biopsy compared with placebo (58% vs 28% P=0.006).
However, neither vitamin E nor metformin improved liver fibrosis, lobular formation, or portal inflammation scores.
There were equal changes in body weight across groups, with the children gaining a mean 13 kg (28.6 lbs) over the 96 weeks of the study -- despite the exercise and diet advice provided.
Lavine and colleagues concluded that while neither vitamin E nor metformin was superior to placebo for sustained ALT reduction, vitamin E improved several histologic markers for children with NASH.
He added that further work needs to be done with regard to the effects of the exercise and dietary intervention used in the trial.
Lavine concluded that the results "reinforce the PIVENS findings that vitamin E improved NASH in adults."
Arun Sanyal, MD, of Virginia Commonwealth University Medical Center in Richmond and president of the AASLD, said that fatty liver disease "is a very scary disease in children," since it is also an emerging risk factor for diabetes and coronary artery disease.
Sanyal, who was also an investigator in the adult PIVENS trial, said the improvement in steatohepatitis seen with vitamin E "is a small step forward in a very important area."
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, as well as the National Institute of Child Health & Human Development.
Vitamin E was provided by Pharmavite.
The researchers reported no conflicts of interest.
Primary source: American Association for the Study of Liver DiseaseSource reference:Lavine JE, et al "Vitamin E, metformin, or placebo treatment of nonalcoholic fatty liver disease in children"
AASLD 2010; Abstract 110
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