Interim results of a pilot study demonstrating the early effects of the PPAR-gamma ligand rosiglitazone on insulin sensitivity, aminotransferases, hepatic steatosis and body weight in patients with non-alcoholic steatohepatitis.
OBJECTIVE
Hyperinsulinemia may cause hepatic steatosis and non-alcoholic steatohepatitis (NASH). The aims of this pilot study were to examine the safety of using the insulin-sensitizing peroxisomal proliferator activated receptor (PPAR) gamma ligand rosiglitazone in patients with NASH and determine whether improved insulin sensitivity correlates with improved fatty liver.


METHODS
Thirty subjects with NASH and elevated alanine aminotransferase (ALT) levels received rosiglitazone, 4 mg twice daily for 48 weeks; the preliminary results presented here were obtained at 24 weeks. Insulin sensitivity was measured using fasting insulin and glucose levels and liver fat content was estimated by CT imaging.


RESULTS
By 24 weeks, rosiglitazone improved insulin sensitivity and reduced liver fat content. The mean ALT decreased from 86 to 37 U/l (P<0.01). Four subjects (13%) withdrew, one because of a rise in ALT from 59 to 277 U/l that coincided with concomitant prednisone use. Subjects experienced a mean weight gain of 3.5% and hemoglobin drop of 1.1 g/dl.


CONCLUSIONS
Treatment of NASH with rosiglitazone for 24 weeks improved insulin sensitivity, reduced liver fat content and improved biochemical evidence of hepatocellular injury. These preliminary data provide evidence that hyperinsulinemia may be a cause of NASH. Strategies to improve insulin sensitivity as a treatment of NASH deserve further investigation.
Neuschwander-Tetri
Brent A
BA
Department of Internal Medicine, Saint Louis University Liver Center, Saint Louis University School of Medicine, 3635 Vista Avenue, St Louis, MO 63110, USA. tetriba@slu.edu
Brunt
Elizabeth M
EM
Wehmeier
Kent R
KR
Sponseller
Craig A
CA
Hampton
Karen
K
Bacon
Bruce R
BR
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D005234:Fatty Liver / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007333:Insulin Resistance; D008024:Ligands; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D010865:Pilot Projects; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage*; D014157:Transcription Factors / Q000378:metabolism*; D016896:Treatment Outcome
D007004:Hypoglycemic Agents; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase