Megan Brooks

November 10, 2009

November 10, 2009 (Boston, Massachusetts) — Supplementation with the natural form of vitamin E (RRR-α-tocopherol) has beneficial effects in patients with nonalcoholic steatohepatitis (NASH), according to findings from a late-breaking study reported here at The Liver Meeting 2009: American Association for the Study of Liver Diseases (AASLD) 60th Annual Meeting.

The findings, from a prospective randomized double-blind placebo-controlled trial, support those from smaller studies of vitamin E in patients with NASH, Arun J. Sanyal, MD, division chair from the Department of Gastroenterology, Hepatology, and Nutrition at Virginia Commonwealth University in Richmond, told meeting attendees.

NASH, for which there is no approved therapy, affects about 4% of the American population, and about 15% of patients with NASH progress to cirrhosis. It is associated with fatty liver disease, insulin resistance, and obesity.

Dr. Sanyal and colleagues studied 247 nondiabetic adults with biopsy-proven NASH with a nonalcoholic fatty liver disease (NAFLD) activity score of 4 or higher within 6 months of randomization. They allocated 80 patients to the insulin-sensitizer pioglitazone (30 mg once daily), 84 to vitamin E (800 IU/day), and 83 to placebo. Liver biopsy was performed before treatment and, in 90% of study subjects, after treatment.

According to Dr. Sanyal, after 96 weeks, 43% of patients in the vitamin E group met the primary end point — an improvement in histology, defined as a decrease in NAFLD activity score of 2 points or more (with a decrease of at least 1 point in cytologic ballooning) and no worsening of fibrosis. This compares to 34% of patients in the pioglitazone group and 19% in the placebo group.

"Pioglitazone did not meet the prespecified level of significance for the primary end point," the researchers note in their abstract.

"Compared with those on placebo, patients on vitamin E had improved steatosis (P = .005), inflammation (P = .02), ballooning scores (P = .01), and serum ALT (P = .001), but no improvement in fibrosis scores," they note.

Pioglitazone was superior to placebo in improving steatosis (P < .001), inflammation (P = .004), ballooning scores (P = .08), and serum ALT (P < .001). There was no improvement in fibrosis scores with pioglitazone.

Patients in the pioglitazone group gained more weight than those in the vitamin E or placebo groups (mean, 4.7 vs 0.4 vs 0.8 kg, respectively; P < .01) but were also the only ones to demonstrate improved insulin resistance (P = .03 vs placebo).

No significant changes in quality of life were evident with either treatment compared with placebo, and there were no drug-related serious adverse effects.

"Not only did vitamin E improve liver function in 40% of the patients treated with it, but the specific type of vitamin E used in the study is inexpensive, readily available, and caused no side effects in patients who participated in the study," Dr. Sanyal noted in a conference-issued statement.

Vitamin E and pioglitazone are both active drugs for the treatment of NASH, Dr. Sanyal told Medscape Gastroenterology. However, he added, "it is important for clinicians to remember that these [treatments] are not a panacea, patients still need to be followed carefully, and the long-term risks of therapy need to be addressed in larger phase 4 studies."

During a press conference highlighting key abstracts, AASLD President Scott L. Friedman, MD, chief of liver diseases at Mount Sinai Medical Center in New York City, said these results show that "when the vitamin E is of sufficient quality that you're really getting antioxidant activity, you will see an impact."

"I think these results should resurrect our efforts to use antioxidants and, more important, to develop very potent antioxidants, which of course are well tolerated in these patients," he added.

Dr. Sanyal reports consulting for Takeda, Salix, Ikaria, Astellas, Pfizer, Gilead, Vertex, Exalenz, Bayer, Onyx, and Amylin; and receiving grant/research support from Sanofi-Aventis, Salix, Gilead, and Intercept. Dr. Friedman reports serving on advisory committees or review panels for Exalenz, Sanofi-Aventis, and Axcan; consulting for Angion, Intercept, 7TM, and Stromedix; and receiving grant/research support from Celera.

The Liver Meeting 2009: American Association for the Study of Liver Diseases (AASLD) 60th Annual Meeting: Late Breaker Abstract LB2. Presented November 2, 2009.

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