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

Abstract

SUMMARY 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.

Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

“…They found that 96-week pioglitazone treatment induced improvement in serum biochemical indices and hepatic pathologic changes. In addition, there are two meta-analyses on thiazolidinediones [71,72]. Both reports showed the efficacy of pioglitazone against hepatic fibrosis.…”

“…Although much clinical, epidemiological, and basic research has aimed to clarify the mechanisms underlying development of NAFLD and NASH, the pathogenesis of NAFLD and NASH is not fully understood; however, oxidative stress is considered to be one of the main players in the development and progression of NAFLD/NASH [72][73][74]. Vitamin E is known as a free radical scavenger, and a chainbreaking antioxidant in free radical reactions, such as lipid peroxidation.…”

Long-term Medical Management of the Liver Transplant Recipient: What the Primary Care Physician Needs to Know

“…32 Thiazolidinediones might have the additional benefit of improved liver biochemistry and histology in patients with NASH. 33 In cases of diabetes that is poorly controlled despite aggressive medical management, the transplant hepatologist may consider withdrawing corticosteroids or possibly adding MMF to reduce CNI or mTOR inhibitor doses. 20 Switching from tacrolimus to cyclosporine has not been reliably effective in reducing glucose levels and has the cost of worse hypertension and dyslipidemia.…”

NAFLD therapy and monitoring disease progression

“…76 A meta-analysis of the use of pioglitazone in NASH has shown improvement of fibrosis with the use of the drug. 80 However, there are concerns regarding the safety of long-term use of thioglitazones. Rosiglitazone has been associated with cardiac ischemia and heart failure.…”