OBJECTIVES

Pioglitazone is an antidiabetic approved in 1999 by the FDA. In the early 2000’s, trials began to determine its efficacy in treating non-alcoholic fatty liver disease (NAFLD). This was based on findings that Type 2 Diabetes Mellitus and NAFLD are related metabolic disorders. This meta-analysis aims to compare pioglitazone to placebo or no treatment for managing liver damage in NAFLD.

METHODS

MEDLINE, EMBASE, and CENTRAL databases were searched for randomized controlled trials (RCTs) and cohort studies published between January 1999 and December 2018. ProQuest, ClinicalTrials.gov, and conference abstracts were also searched. Eligible population was restricted to NAFLD patients diagnosed by liver biopsy as the gold standard for diagnosis. Outcome measure was improvement in liver histology scores which encompass (steatosis, hepatocellular ballooning, lobular inflammation, and fibrosis). A meta-analysis was performed using RevMan to determine the pooled odds ratios (OR), the corresponding 95% confidence intervals (95% CI), and heterogeneity level (I²). Studies quality was assessed using the Cochrane Risk of Bias tool for RCTs and Newcastle-Ottawa Quality Assessment Scale for cohort studies if applicable.

RESULTS

Four published RCTs were identified and included in this analysis. Pooling their findings showed that use of pioglitazone had better outcomes compared to placebo as presented in the following OR and 95% CI: Steatosis, 3.86 (2.16-6.91), I²=39%; lobular inflammation, 3.07 (1.99-4.74), I²=0%; hepatocellular ballooning, 2.63 (1.67-4.13), I²=0%; and fibrosis, 1.76 (1.14-2.72), I²=0%. Sub-group analysis of studies which included patients with comorbid diabetes showed greater odds for reduction in histology scores with pioglitazone use: Steatosis, 5.10 (2.40-10.83); lobular inflammation, 3.96 (1.94-8.07); hepatocellular ballooning, 3.39 (1.67-6.88); and fibrosis, 1.87 (0.94-3.72).

CONCLUSIONS

Pioglitazone administration to NAFLD patients is associated with improved liver histology compared to placebo. Available evidence supports an added benefit of prescribing pioglitazone to patients with both diabetes and NAFLD.