Premium
Effects of ursodeoxycholic acid in combination with vitamin E on adipokines and apoptosis in patients with nonalcoholic steatohepatitis
Author(s) -
Balmer Maria Luisa,
Siegrist Kathrin,
Zimmermann Arthur,
Dufour JeanFrançois
Publication year - 2009
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2009.02037.x
Subject(s) - adiponectin , adipokine , medicine , ursodeoxycholic acid , endocrinology , steatohepatitis , steatosis , resistin , fatty liver , insulin resistance , insulin , disease
Background/Aims: 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‐α 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.