Effects of vitamin E treatment on peroxisome proliferator-activated receptor-alpha expression and insulin resistance in patients with non-alcoholic steatohepatitis: results of a pilot study

Abstract

Background: Insulin resistance (IR) is commonly associated with non-alcoholic steatohepatitis (NASH). Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) may also play a role in the pathogenesis of NASH. A pivotal role in NASH pathogenesis depends on the hypothesis of increased oxidative stress. The aim of our study was to evaluate the effects of supplemental oral vitamin E, a potent antioxidant, on liver functions, PPAR-alpha expression and IR in patients with NASH. Methods: Nine patients with biopsy-proven NASH were given oral vitamin E 800 mg daily for 24 weeks. Liver functions, lipid parameters, IR index with homeostatic metabolic assessment and liver histology and PPAR-alpha staining index in biopsy specimens were detected before and after the treatment. Results: Seven patients (78%) had IR initially. After 6 months of therapy in nine patients, fasting insulin improved (P = 0.01), but serum cholesterol, triglyceride, fasting blood glucose levels and body mass index remained unchanged. Aspartate aminotransferase and alanine aminotransferase levels decreased (P = 0.01 and P = 0.01, respectively). IR index with homeostatic metabolic assessment resistance improved (P = 0.01), but PPAR-alpha staining index did not change (P = 0.37). Although the histological grade of steatosis decreased (P = 0.01), necroinflammation and fibrosis remained unchanged. In seven patients with IR, however, necroinflammation and PPAR-alpha staining index were improved (P = 0.04 and P = 0.02). Conclusion: Vitamin E treatment, in addition to its previously shown beneficial effect by suppressing oxidative stress, may also achieve improvement by reducing IR and PPAR-alpha expression in NASH.