Introduction: Exogenous administration of recombinant irisin may reverse hepatic steatosis and steatohepatitis. However, it remains controversial as to whether nonalcoholic fatty liver disease (NAFLD) shows reduced circulating (serum/plasma) irisin levels. A meta-analysis was conducted to address this issue.

Material and methods: A literature search of databases was performed up to June 2021. Observational studies that reported circulating irisin in NAFLD ascertained by any methods (e.g. ultrasonography or magnetic resonance) and compared with any controls were eligible for inclusion. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were obtained using a random-effects meta-analysis model.

Results: Eleven studies enrolling 1277 NAFLD cases and 944 non-NAFLD controls were included. The approaches used for NAFLD ascertainment included ultrasonography (4 studies), magnetic resonance (3 studies), and liver biopsy (5 studies). Meta-analysis showed that circulating irisin in NAFLD was comparable to any non-NAFLD controls (10 studies with 11 datasets; SMD –0.09, 95% CI: –0.48 to 0.29), including the body mass index (BMI)-matched and lean controls (both p ≥ 0.80). Restricting studies to NAFLD ascertained by magnetic resonance or liver biopsy rather than ultrasonography showed that serum irisin was reduced in NAFLD (5 studies, SMD –0.63, 95% CI: –1.14 to –0.13). Meta-analysis also suggested that circulating irisin did not differ between mild and moderate-to-severe NAFLD (7 studies; SMD 0.02, 95% CI: –0.25 to 0.30), and this association was not significantly moderated by study location (Europe versus Asia).

Conclusions: Circulating irisin in NAFLD did not differ from any non-NAFLD controls and was unlikely to be affected by disease severity or racial-ethnic difference.