Meta-analysis: pioglitazone improves liver histology and fibrosis in patients with non-alcoholic steatohepatitis

Aliment Pharmacol Ther. 2012 Jan;35(1):66-75. doi: 10.1111/j.1365-2036.2011.04912.x. Epub 2011 Nov 4.


Background: Thiazolidinediones (TZDs) have been used in the treatment of non-alcoholic steatohepatitis (NASH). However, the magnitude of treatment response associated with TZDs in improving liver histology in NASH has not been quantified systematically.

Aim: To conduct a meta-analysis of randomised, placebo-controlled clinical trials (RPCTs) using pioglitazone and rosiglitazone in the treatment of NASH.

Methods: Pubmed/MEDLINE and Cochrane Central Register of Controlled Trials 2010 were searched until September 2010 and four RPCTs were identified. Peto odds ratios (ORs) and their respective 95% confidence intervals (CIs) were used to assess the efficacy of TZDs in improving liver histological parameters.

Results: Four good quality RPCTs derived from three continents were included. The meta-analysis showed that TZDs (n = 169) were significantly better than placebo (n = 165) in improving ballooning degeneration, lobular inflammation and steatosis with combined ORs of 2.11 (95% CI, 1.33-3.36), 2.58 (95% CI, 1.68-3.97) and 3.39 (95% CI, 2.19-5.25) respectively. The improvement in combined necroinflammation with TZD (n = 58) vs. placebo (n = 52) was also statistically significant (combined OR 6.52[95% CI, 3.03-14.06]), but improvement in fibrosis was not. When pioglitazone (n = 137) was analysed alone, the improvement in fibrosis with pioglitazone (n = 137) vs. placebo (n = 134) (combined OR 1.68 [95% CI, 1.02-2.77]) was statistically significant. The total body fat slightly decreased in the control, while it markedly and highly significantly increased with TZD treatment.

Conclusions: Thiazolidinediones significantly improve ballooning degeneration, lobular inflammation, steatosis and combined necroinflammation in patients with NASH. Pioglitazone may improve fibrosis. Larger randomised, placebo-controlled clinical trials are needed to examine the efficacy of thiazolidinediones in improving NASH fibrosis.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fatty Liver / complications
  • Fatty Liver / drug therapy*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Liver / drug effects*
  • Liver Cirrhosis / drug therapy*
  • Non-alcoholic Fatty Liver Disease
  • Pioglitazone
  • Randomized Controlled Trials as Topic
  • Thiazolidinediones / therapeutic use*


  • Hypoglycemic Agents
  • Thiazolidinediones
  • Pioglitazone