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.
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).


CONCLUSIONS
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.
Yakaryilmaz
F
F
Department of Internal Medicine, Division of Gastroenterology, University of Kirikkale, School of Medicine, Kirikkale, Turkey. fahriyy67@yahoo.com
Guliter
S
S
Savas
B
B
Erdem
O
O
Ersoy
R
R
Erden
E
E
Akyol
G
G
Bozkaya
H
H
Ozenirler
S
S
D005234:Fatty Liver / Q000150:complications*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D016877:Oxidants / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D047493:PPAR alpha / Q000096:biosynthesis*; D010865:Pilot Projects; D014810:Vitamin E / Q000627:therapeutic use*
D016877:Oxidants; D047493:PPAR alpha; D014810:Vitamin E