title: Drugs improving insulin resistance for non-alcoholic fatty liver disease and/or non-alcoholic steatohepatitis.
abstract: BACKGROUND
  Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver, which may progress to non-alcoholic steatohepatitis (NASH) and cirrhosis. It is suspected in persons with elevated aminotransferase levels and features of insulin resistance (or metabolic) syndrome. The pathogenesis of NAFLD is not clear and there is no universal treatment.
  
  
  OBJECTIVE
  To assess beneficial and harmful effects of drugs improving insulin resistance for NAFLD and/or NASH.
  
  
  METHODS
  We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and The Chinese Biomedical Database until February 2006.
  
  
  METHODS
  We included randomised clinical trials assessing the effects of drugs improving insulin resistance for patients with NAFLD or NASH.
  
  
  METHODS
  We evaluated the methodological quality of the randomised clinical trials by the generation of the allocation section, allocation concealment, and follow-up. Two independent observers extracted data from each trial. Dichotomous outcomes were reported as odds ratio (OR) with 95% confidence interval (CI).
  
  
  RESULTS
  Only three randomised clinical trials could be included. Two of the trials had unclear allocation concealment. None was blinded regarding outcome assessment. In two trials, metformin was associated with significantly higher normalization of serum alanine aminotransferase (OR fixed 2.83, 95% CI 1.27 to 6.31 versus diet and OR fixed 7.75, 95% CI 2.37 to 25.35 versus vitamin E) and improvement of liver echographic response (OR fixed 5.25, 95% CI 1.09 to 25.21). An improvement of fatty infiltration was observed in a limited number of patients undergoing liver biopsy. In the single pioglitazone trial, a statistically significant improvement of NASH histology was demonstrated.
  
  
  CONCLUSIONS
  At present, there is insufficient data to either support or refute the use of drugs improving insulin resistance for patients with NAFLD, although current limited information suggests a favourable role of drugs improving insulin resistance. It is advisable to carry out large randomised trials on this topic employing clinically relevant outcome measures and adequate methodology, including blinded outcome assessment.
authors.affiliation: IV Divisione di Clinica Medica - Policlinico Umberto 1, Dipartimento di Medicina Sperimentale e Patologia, Centro per l'Atero-trombosi, Università La Sapienza, viale del Policlinico 155, Rome, Italy, 00161. francesco.angelico@uniroma1.it
authors.forename: F
authors.initials: F
authors.lastname: Angelico
authors.forename: M
authors.initials: M
authors.lastname: Burattin
authors.forename: C
authors.initials: C
authors.lastname: Alessandri
authors.forename: M
authors.initials: M
authors.lastname: Del Ben
authors.forename: F
authors.initials: F
authors.lastname: Lirussi
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D005234:Fatty Liver / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance; D008687:Metformin / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D014810:Vitamin E / Q000627:therapeutic use; D014815:Vitamins / Q000627:therapeutic use
chemical_list: D007004:Hypoglycemic Agents; D014815:Vitamins; D014810:Vitamin E; D008687:Metformin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase