Effects of ursodeoxycholic acid in combination with vitamin E on adipokines and apoptosis in patients with nonalcoholic steatohepatitis.
OBJECTIVE
Adipokines and hepatocellular apoptosis participate in the pathogenesis of nonalcoholic steatohepatitis (NASH). In a randomized trial ursodeoxycholic acid (UDCA) with vitamin E (VitE) improved serum aminotransferases and hepatic histology. The present work evaluates the effect of this combination on adipokines and hepatocellular apoptosis.


METHODS
Circulating levels of adiponectin, resistin, leptin, interleukin (IL)-6, IL-8, retinol binding protein-4, monocyte chemoattractant protein-1 and tumour necrosis factor-alpha were measured by enzyme-linked immunoassays at the beginning and after 2 years of treatment with either UDCA+VitE, UDCA+placebo (P) or P+P. Apoptosis was assessed by immunohistochemistry for activated caspase-3 and circulating levels of apoptosis-associated cytokeratin 18 fragments (M30).


RESULTS
Levels of adiponectin increased in patients treated with UDCA+VitE, whereas they decreased in the two other groups (P<0.04) and correlated with the improvement of liver steatosis (P<0.04). M30 levels worsened in the P/P group and improved in the other two groups. They correlated with hepatocellular apoptosis (P<0.02) and steatosis (P<0.02) as well as negatively with adiponectin levels (P<0.04).


CONCLUSIONS
UDCA+VitE improves not only aminotransferase levels and liver histology of patients with NASH, but also decreases hepatocellular apoptosis and restores circulating levels of adiponectin. These results suggest that the UDCA+VitE combination has metabolic effects in addition to its beneficial cytoprotective properties.
Balmer
Maria Luisa
ML
Institute of Clinical Pharmacology and Visceral Research, University of Berne, Berne, Switzerland.
Siegrist
Kathrin
K
Zimmermann
Arthur
A
Dufour
Jean-François
JF
D054392:Adipokines / Q000097:blood*; D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002793:Cholic Acids / Q000627:therapeutic use*; D019610:Cytoprotection / Q000187:drug effects*; D004359:Drug Therapy, Combination; D005234:Fatty Liver / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014810:Vitamin E / Q000627:therapeutic use*; D055815:Young Adult
D054392:Adipokines; D000975:Antioxidants; D002793:Cholic Acids; D014810:Vitamin E; C030712:ursocholic acid